Brief Summary
Polycythemia vera (PV) is a long-term condition in which the bone marrow makes too many red blood cells (RBCs). Bone marrow is the soft tissue inside the large bones where blood cells are made. When there are too many RBCs, called erythrocytosis, the blood can become thicker and move less easily through blood vessels and organs. This can raise the risk of blood clots (thrombosis) in veins or arteries. Sometimes, these clots can be life-threatening and may cause a stroke or heart attack. Treatment aims to keep the percentage of RBCs in the blood (hematocrit) in a safe range. For adults with PV, this means keeping the hematocrit below 45%. This helps lower the blood thickness and the risk of thrombosis. PV can also be linked to low iron levels (iron deficiency), because the body uses iron to make more RBCs. Many people with PV are treated with blood removal (phlebotomy) to lower RBC levels in the blood. This can worsen the iron deficiency, because each blood removal also takes iron out of the body.
Rusfertide is a medicine that lowers the amount of iron available in the blood. It works like hepcidin, a natural hormone that helps control iron levels in the body. By limiting iron available for RBC production, rusfertide may help keep hematocrit below 45% and may improve symptoms. It may also reduce, or even remove, the need for phlebotomy in people.
The main aim of this study is to check how well rusfertide works compared with placebo to lower the number of phlebotomies. A placebo looks like rusfertide but does not have any medicine in it.
Other aims are to learn how safe rusfertide is compared with placebo and to understand how well it works to reduce the need for phlebotomy and to keep hematocrit levels under control. The study also wants to learn how rusfertide moves through the body (pharmacokinetics) and how it affects the body (pharmacodynamics or PD).
This study has 4 parts that follow each other:
* In part 1a, participants will receive either rusfertide or placebo.
* In part 1b, all participants will receive rusfertide.
* In part 2, participants can continue to receive rusfertide if they benefit from treatment with rusfertide.
* Part 3 will include participants who finish Part 2 and still benefit from rusfertide.
During the study, participants will visit the study clinical several times at fixed timepoints.
Rusfertide is a medicine that lowers the amount of iron available in the blood. It works like hepcidin, a natural hormone that helps control iron levels in the body. By limiting iron available for RBC production, rusfertide may help keep hematocrit below 45% and may improve symptoms. It may also reduce, or even remove, the need for phlebotomy in people.
The main aim of this study is to check how well rusfertide works compared with placebo to lower the number of phlebotomies. A placebo looks like rusfertide but does not have any medicine in it.
Other aims are to learn how safe rusfertide is compared with placebo and to understand how well it works to reduce the need for phlebotomy and to keep hematocrit levels under control. The study also wants to learn how rusfertide moves through the body (pharmacokinetics) and how it affects the body (pharmacodynamics or PD).
This study has 4 parts that follow each other:
* In part 1a, participants will receive either rusfertide or placebo.
* In part 1b, all participants will receive rusfertide.
* In part 2, participants can continue to receive rusfertide if they benefit from treatment with rusfertide.
* Part 3 will include participants who finish Part 2 and still benefit from rusfertide.
During the study, participants will visit the study clinical several times at fixed timepoints.
Brief Title
A Study of Rusfertide in Adults With Polycythemia Vera (PV)
Categories
Completion Date
Completion Date Type
Estimated
Conditions
POLYCYTHEMIA VERA
Eligibility Criteria
Inclusion criteria:
1. Male and female participants aged 18 (or the minimum country specific age of consent if greater than \[\>\]18) years or older.
2. Participant understands the study procedures, is willing and able to adhere to study requirements and agrees to participate in the study by giving written informed consent.
3. Meet revised 2016 World Health Organization (WHO) criteria for the diagnosis of PV.
4. Phlebotomy requiring defined as ALL of the following:
1. At least 3 phlebotomies due to inadequate hematocrit control in 28 weeks before randomization or at least 5 phlebotomies due to inadequate hematocrit control in 1 year before randomization, and
2. Last phlebotomy due to inadequate hematocrit control within 3 months before randomization, and
3. No phlebotomy within 6 days prior to randomization (do not include day of phlebotomy and day of randomization in the 6-day count).
5. Complete blood count (CBC) values immediately prior to randomization:
1. Hematocrit \<45%,
2. White blood cell count (WBC) 4000 cells per microlitre (/μL) to 20,000/μL (inclusive), and
3. Platelets 100,000/μL to 1,000,000/μL (inclusive).
6. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2.
7. Women of childbearing potential (WOCBP) agree to use medically acceptable contraception (\<1% annual failure rate) during the study and for 30 days after the last dose of study drug.
8. A female participant must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for a period of 30 days after receiving the last dose of study medication.
9. Men with partners of childbearing potential agree to use medically acceptable contraception (\<1% annual failure rate) during the study and for 90 days after the last dose of study drug. In addition, men must use a condom during the study and for 90 days after the last dose of study drug regardless of the partner's childbearing potential.
10. A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 90 days after receiving the last dose.
11. Participants receiving cytoreductive therapy at randomization must be on a stable PV therapy regimen as follows:
1. Hydroxyurea - at least 2 months
2. Janus kinase (JAK) inhibitor - at least 2 months
3. Interferon - at least 6 months.
12. Participants treated with phlebotomy alone at randomization must have stopped:
1. Hydroxyurea at least 2 months before screening
2. JAK inhibitor at least 2 months before screening
3. Interferon at least 6 months before screening.
Exclusion criteria:
1. Clinically meaningful laboratory abnormalities at Screening, including but not limited to the following:
1. Estimated glomerular filtration rate (eGFR) \<15 milliliters per minute per 1.73 square meters (mL/min/1.73 m\^2)
2. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥2.5×upper limit of normal (ULN)
3. Total bilirubin \>1.5×ULN
2. Participants who required phlebotomy at HCT levels lower than 45%.
3. Pregnant or lactating females.
4. Clinically significant thrombosis (e.g., deep vein thrombosis or splenic vein thrombosis) within 2 months prior to randomization.
5. Active or chronic bleeding within 2 months prior to randomization.
6. Met the criteria for post-PV myelofibrosis as defined by the International Working Group-Myeloproliferative Neoplasms Research and Treatment.
7. Any infection requiring systemic therapy within 1 month of dosing except controlled human immunodeficiency virus (HIV), hepatitis B, and hepatitis C. Prophylactic therapies were allowed.
8. Any serious or unstable medical condition (e.g., poorly controlled HIV infection) or uncontrolled psychiatric condition as judged by the Investigator that would impair the participant's ability to participate in the study.
9. Major surgical procedure within 2 months prior to randomization unless the participant had fully recovered from surgery or planned major elective surgery during the study.
10. History of invasive malignancies within the last 5 years, except
1. localized cured cancer (e.g., prostate cancer and cervical cancer)
2. localized cured in situ or Stage 1 squamous cell carcinoma (SCC) of the skin, basal cell carcinoma (BCC) of the skin, or in situ melanoma of the skin.
11. Participants with in situ or Stage 1 SCC of the skin, in situ or Stage 1 BCC of the skin, or in situ melanoma of the skin identified during the required dermatology examination at Screening unless the cancer was adequately treated (i.e., treatment that was expected to be curative, such as Mohs surgery) before randomization. Note: Suspicious lesions were to be biopsied and results made available before randomization.
12. Participants with active alcohol or drug addiction that would have interfered with their ability to comply with study requirements.
13. Participants who did not complete at least 4 days of MFSAF assessments within 1 week prior to randomization.
14. Receipt of an investigational agent within 2 months or 5 half-lives, whichever was longer, prior to randomization.
15. Received busulfan, pipobroman, or 32Phosphorus within 7 months prior to Screening.
16. Participants with hypersensitivity to rusfertide or to any of the excipients or placebo.
17. Participants with any lesion or mass detected by physical examination or imaging during screening that was suspicious for malignancy unless evaluated and assessed to be not malignant.
1. Male and female participants aged 18 (or the minimum country specific age of consent if greater than \[\>\]18) years or older.
2. Participant understands the study procedures, is willing and able to adhere to study requirements and agrees to participate in the study by giving written informed consent.
3. Meet revised 2016 World Health Organization (WHO) criteria for the diagnosis of PV.
4. Phlebotomy requiring defined as ALL of the following:
1. At least 3 phlebotomies due to inadequate hematocrit control in 28 weeks before randomization or at least 5 phlebotomies due to inadequate hematocrit control in 1 year before randomization, and
2. Last phlebotomy due to inadequate hematocrit control within 3 months before randomization, and
3. No phlebotomy within 6 days prior to randomization (do not include day of phlebotomy and day of randomization in the 6-day count).
5. Complete blood count (CBC) values immediately prior to randomization:
1. Hematocrit \<45%,
2. White blood cell count (WBC) 4000 cells per microlitre (/μL) to 20,000/μL (inclusive), and
3. Platelets 100,000/μL to 1,000,000/μL (inclusive).
6. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2.
7. Women of childbearing potential (WOCBP) agree to use medically acceptable contraception (\<1% annual failure rate) during the study and for 30 days after the last dose of study drug.
8. A female participant must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for a period of 30 days after receiving the last dose of study medication.
9. Men with partners of childbearing potential agree to use medically acceptable contraception (\<1% annual failure rate) during the study and for 90 days after the last dose of study drug. In addition, men must use a condom during the study and for 90 days after the last dose of study drug regardless of the partner's childbearing potential.
10. A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 90 days after receiving the last dose.
11. Participants receiving cytoreductive therapy at randomization must be on a stable PV therapy regimen as follows:
1. Hydroxyurea - at least 2 months
2. Janus kinase (JAK) inhibitor - at least 2 months
3. Interferon - at least 6 months.
12. Participants treated with phlebotomy alone at randomization must have stopped:
1. Hydroxyurea at least 2 months before screening
2. JAK inhibitor at least 2 months before screening
3. Interferon at least 6 months before screening.
Exclusion criteria:
1. Clinically meaningful laboratory abnormalities at Screening, including but not limited to the following:
1. Estimated glomerular filtration rate (eGFR) \<15 milliliters per minute per 1.73 square meters (mL/min/1.73 m\^2)
2. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥2.5×upper limit of normal (ULN)
3. Total bilirubin \>1.5×ULN
2. Participants who required phlebotomy at HCT levels lower than 45%.
3. Pregnant or lactating females.
4. Clinically significant thrombosis (e.g., deep vein thrombosis or splenic vein thrombosis) within 2 months prior to randomization.
5. Active or chronic bleeding within 2 months prior to randomization.
6. Met the criteria for post-PV myelofibrosis as defined by the International Working Group-Myeloproliferative Neoplasms Research and Treatment.
7. Any infection requiring systemic therapy within 1 month of dosing except controlled human immunodeficiency virus (HIV), hepatitis B, and hepatitis C. Prophylactic therapies were allowed.
8. Any serious or unstable medical condition (e.g., poorly controlled HIV infection) or uncontrolled psychiatric condition as judged by the Investigator that would impair the participant's ability to participate in the study.
9. Major surgical procedure within 2 months prior to randomization unless the participant had fully recovered from surgery or planned major elective surgery during the study.
10. History of invasive malignancies within the last 5 years, except
1. localized cured cancer (e.g., prostate cancer and cervical cancer)
2. localized cured in situ or Stage 1 squamous cell carcinoma (SCC) of the skin, basal cell carcinoma (BCC) of the skin, or in situ melanoma of the skin.
11. Participants with in situ or Stage 1 SCC of the skin, in situ or Stage 1 BCC of the skin, or in situ melanoma of the skin identified during the required dermatology examination at Screening unless the cancer was adequately treated (i.e., treatment that was expected to be curative, such as Mohs surgery) before randomization. Note: Suspicious lesions were to be biopsied and results made available before randomization.
12. Participants with active alcohol or drug addiction that would have interfered with their ability to comply with study requirements.
13. Participants who did not complete at least 4 days of MFSAF assessments within 1 week prior to randomization.
14. Receipt of an investigational agent within 2 months or 5 half-lives, whichever was longer, prior to randomization.
15. Received busulfan, pipobroman, or 32Phosphorus within 7 months prior to Screening.
16. Participants with hypersensitivity to rusfertide or to any of the excipients or placebo.
17. Participants with any lesion or mass detected by physical examination or imaging during screening that was suspicious for malignancy unless evaluated and assessed to be not malignant.
Inclusion Criteria
Inclusion criteria:
1. Male and female participants aged 18 (or the minimum country specific age of consent if greater than \[\>\]18) years or older.
2. Participant understands the study procedures, is willing and able to adhere to study requirements and agrees to participate in the study by giving written informed consent.
3. Meet revised 2016 World Health Organization (WHO) criteria for the diagnosis of PV.
4. Phlebotomy requiring defined as ALL of the following:
1. At least 3 phlebotomies due to inadequate hematocrit control in 28 weeks before randomization or at least 5 phlebotomies due to inadequate hematocrit control in 1 year before randomization, and
2. Last phlebotomy due to inadequate hematocrit control within 3 months before randomization, and
3. No phlebotomy within 6 days prior to randomization (do not include day of phlebotomy and day of randomization in the 6-day count).
5. Complete blood count (CBC) values immediately prior to randomization:
1. Hematocrit \<45%,
2. White blood cell count (WBC) 4000 cells per microlitre (/μL) to 20,000/μL (inclusive), and
3. Platelets 100,000/μL to 1,000,000/μL (inclusive).
6. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2.
7. Women of childbearing potential (WOCBP) agree to use medically acceptable contraception (\<1% annual failure rate) during the study and for 30 days after the last dose of study drug.
8. A female participant must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for a period of 30 days after receiving the last dose of study medication.
9. Men with partners of childbearing potential agree to use medically acceptable contraception (\<1% annual failure rate) during the study and for 90 days after the last dose of study drug. In addition, men must use a condom during the study and for 90 days after the last dose of study drug regardless of the partner's childbearing potential.
10. A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 90 days after receiving the last dose.
11. Participants receiving cytoreductive therapy at randomization must be on a stable PV therapy regimen as follows:
1. Hydroxyurea - at least 2 months
2. Janus kinase (JAK) inhibitor - at least 2 months
3. Interferon - at least 6 months.
12. Participants treated with phlebotomy alone at randomization must have stopped:
1. Hydroxyurea at least 2 months before screening
2. JAK inhibitor at least 2 months before screening
3. Interferon at least 6 months before screening.
1. Male and female participants aged 18 (or the minimum country specific age of consent if greater than \[\>\]18) years or older.
2. Participant understands the study procedures, is willing and able to adhere to study requirements and agrees to participate in the study by giving written informed consent.
3. Meet revised 2016 World Health Organization (WHO) criteria for the diagnosis of PV.
4. Phlebotomy requiring defined as ALL of the following:
1. At least 3 phlebotomies due to inadequate hematocrit control in 28 weeks before randomization or at least 5 phlebotomies due to inadequate hematocrit control in 1 year before randomization, and
2. Last phlebotomy due to inadequate hematocrit control within 3 months before randomization, and
3. No phlebotomy within 6 days prior to randomization (do not include day of phlebotomy and day of randomization in the 6-day count).
5. Complete blood count (CBC) values immediately prior to randomization:
1. Hematocrit \<45%,
2. White blood cell count (WBC) 4000 cells per microlitre (/μL) to 20,000/μL (inclusive), and
3. Platelets 100,000/μL to 1,000,000/μL (inclusive).
6. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2.
7. Women of childbearing potential (WOCBP) agree to use medically acceptable contraception (\<1% annual failure rate) during the study and for 30 days after the last dose of study drug.
8. A female participant must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for a period of 30 days after receiving the last dose of study medication.
9. Men with partners of childbearing potential agree to use medically acceptable contraception (\<1% annual failure rate) during the study and for 90 days after the last dose of study drug. In addition, men must use a condom during the study and for 90 days after the last dose of study drug regardless of the partner's childbearing potential.
10. A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 90 days after receiving the last dose.
11. Participants receiving cytoreductive therapy at randomization must be on a stable PV therapy regimen as follows:
1. Hydroxyurea - at least 2 months
2. Janus kinase (JAK) inhibitor - at least 2 months
3. Interferon - at least 6 months.
12. Participants treated with phlebotomy alone at randomization must have stopped:
1. Hydroxyurea at least 2 months before screening
2. JAK inhibitor at least 2 months before screening
3. Interferon at least 6 months before screening.
Gender
All
Gender Based
false
Keywords
Polycythemia Vera
PV
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT05210790
Org Class
Industry
Org Full Name
Protagonist Therapeutics, Inc.
Org Study Id
PTG-300-11
Overall Status
Active, not recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 3 Study of the Hepcidin Mimetic Rusfertide (PTG-300; TAK-121) in Patients With Polycythemia Vera
Primary Outcomes
Outcome Description
Response was defined as absence of phlebotomy eligibility. Phlebotomy eligibility was defined as either: 1) A confirmed hematocrit (HCT) greater than or equal to (≥) 45% that was at least 3% higher than the baseline HCT, where confirmation was defined as 2 consecutive HCT assessments that were ≥ 45% and at least 3% higher than the baseline HCT, or 2) HCT ≥ 48%.
Outcome Measure
Part 1a: Percentage of Participants Who Achieved Response
Outcome Time Frame
From Weeks 20 to 32
Secondary Ids
Secondary Id
2023-509750-58-00
Secondary Id
2023
Secondary Outcomes
Outcome Time Frame
Baseline to Week 32
Outcome Measure
Part 1a: Number of Phlebotomies
Outcome Time Frame
Baseline to Week 32
Outcome Measure
Part 1a: Percentage of Participants With All Hematocrit Values < 45%
Outcome Description
The PROMIS Fatigue SF 8a T-score will be obtained via the item-response theory (IRT) response-pattern scoring approach using the PROMIS Scoring Service available at https://www.assessmentcenter.net/ac\_scoringservice. It is an National Institutes of Health (NIH)-developed fatigue survey of 8 items that asks the participant about fatigue experience and impact over the past 7 days. Each item will be scored on a 5-point Likert scale (1=never/not at all to 5=almost always/very much). Raw scores (range: 8-40) will be converted into standardized T scores (range: 34.1-80.9), with higher scores indicating greater fatigue severity. A negative change from baseline indicates an improvement.
Outcome Time Frame
Baseline, Week 32
Outcome Measure
Part 1a: Change From Baseline in the Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form 8a Total T-score
Outcome Description
The MFSAF version 4.0 (v4.0) TSS7 is a questionnaire developed by the Patient-Reported Outcome (PRO) Consortium's Myelofibrosis Working Group that focuses on the 7 core symptoms of myelofibrosis: fatigue, night sweats, pruritus, abdominal discomfort, pain under the ribs on the left side, early satiety, and bone pain. It includes 7 items on a 0 (absent) to 10 (worst imaginable) numeric rating scale. A higher score indicates worse symptoms. A negative change from baseline indicates an improvement.
Outcome Time Frame
Baseline, Week 32
Outcome Measure
Part 1a: Change From Baseline in the Myelofibrosis Symptom Assessment Form (MFSAF) Version 4.0 Total Symptom Score-7 (TSS7) Items
Outcome Description
The PROMIS Fatigue SF 8a T-score will be obtained via the IRT response-pattern scoring approach using the PROMIS Scoring Service available at https://www.assessmentcenter.net/ac\_scoringservice. It is a National Institutes of Health (NIH)-developed fatigue survey of 8 items that asks the participant about fatigue experience and impact over the past 7 days. Each item will be scored on a 5-point Likert scale (1=never/not at all to 5=almost always/very much). Raw scores (range: 8-40) will be converted into standardized T scores (range: 34.1-80.9), with higher scores indicating greater fatigue severity. Moderate or severe symptoms are defined as a baseline PROMIS Fatigue SF 8aT-score \>/= 58.8. A negative change from baseline indicates an improvement.
Outcome Time Frame
Baseline, Week 32
Outcome Measure
Part 1a: Change From Baseline in the PROMIS Fatigue Short Form 8a Total T-score Among Participants Who Have Moderate or Severe Symptoms at Baseline
Outcome Description
The MFSAF v4.0 is a questionnaire developed by the PRO Consortium's Myelofibrosis Working Group that focused on the 7 core symptoms of myelofibrosis: fatigue, night sweats, pruritus, abdominal discomfort, pain under the ribs on the left side, early satiety, and bone pain. Items are scored on a 0 (absent) to 10 (worst imaginable) numeric rating scale. The MFSAF TSS4 is the sum of four items in the MFSAF (fatigue, itching \[pruritis\], night sweats, and abdominal discomfort). The weekly TSS4 will be calculated by averaging daily scores over a 7-day interval leading to Week 32 (inclusive). Moderate or severe symptoms are defined as a baseline MFSAF TSS4 \>/=9.1. A higher score indicates worse symptoms. A negative change from baseline indicates an improvement.
Outcome Time Frame
Baseline, Week 32
Outcome Measure
Part 1a: Change From Baseline in the MFSAF Total Symptom Score-4 Items (TSS4) Among Participants Who Have Moderate or Severe Symptoms at Baseline
Outcome Description
MPN-SAF is a 10-item questionnaire measurement tool for symptoms of MPNs. Moderate or severe symptoms are defined as baseline MPN-SAF problems with concentration ≥4. The descriptive analysis approach the distribution of the MPN-SAF problems with concentration at Baseline will be categorized using the Patient Global Impression of Severity (PGI-S). The response quartiles will be used to establish the recommended cut-off points for the MPN-SAF Problems with Concentration corresponding to "none" or "mild" versus "moderate or "severe" categories on the PGI-S.
Outcome Time Frame
Baseline, Week 32
Outcome Measure
Part 1a: Change From Baseline in the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) Problems With Concentration Among Participants Who Have Moderate or Severe Symptoms at Baseline
Outcome Description
The PROMIS Fatigue SF 8a T-score will be obtained via the IRT response-pattern scoring approach using the PROMIS Scoring Service available at https://www.assessmentcenter.net/ac\_scoringservice. It is an NIH-developed fatigue survey of 8 items that asks the participant about fatigue experience and impact over the past 7 days. Each item will be scored on a 5-point Likert scale (1=never/not at all to 5=almost always/very much). Raw scores (range: 8-40) will be converted into standardized T scores (range: 34.1-80.9), with higher scores indicating greater fatigue severity. Moderate or severe symptoms are defined as a baseline PROMIS Fatigue SF 8aT-score \>/= 58.8.
Outcome Time Frame
At Week 32
Outcome Measure
Part 1a: Percentage of Participants With a Meaningful Within-person Change at Week 32 in the PROMIS Fatigue SF 8a Total T-score Among Participants Who Have Moderate or Severe Symptoms at Baseline
Outcome Description
The MFSAF v4.0 is a questionnaire developed by the PRO Consortium's Myelofibrosis Working Group that focuses on the 7 core symptoms of myelofibrosis: fatigue, night sweats, pruritus, abdominal discomfort, pain under the ribs on the left side, early satiety, and bone pain. It included 7 items on a 0 (absent) to 10 (worst imaginable) numeric rating scale. The MFSAF TSS4 is the sum of four items in the MFSAF (fatigue, itching \[pruritis\], night sweats, and abdominal discomfort). The weekly TSS4 will be calculated by averaging daily scores over a 7-day interval leading to Week 32 (inclusive). Moderate or severe symptoms are defined as a baseline MFSAF TSS4 \>/=9.1.
Outcome Time Frame
At Week 32
Outcome Measure
Part 1a: Percentage of Participants With a Meaningful Within-person Change at Week 32 in the MFSAF TSS4 Among Participants Who Had Moderate or Severe Symptoms at Baseline
Outcome Description
MPN-SAF is a 10-item questionnaire measurement tool for symptoms of MPNs. Moderate or severe symptoms are defined as baseline MPN-SAF problems with concentration ≥4. The descriptive analysis approach the distribution of the MPN-SAF problems with concentration at Baseline was categorized using the PGI-S. The response quartiles were used to establish the recommended cut-off points for the MPN-SAF Problems with Concentration corresponding to "none" or "mild" versus "moderate or "severe" categories on the PGI-S.
Outcome Time Frame
At Week 32
Outcome Measure
Part 1a: Percentage of Participants With a Meaningful Within-person Change at Week 32 in the MPN-SAF Problems With Concentration Among Participants Who Had Moderate or Severe Symptoms at Baseline
Outcome Description
The PROMIS Fatigue SF 8a T-score will be obtained via the IRT response-pattern scoring approach using the PROMIS Scoring Service available at https://www.assessmentcenter.net/ac\_scoringservice. It is an NIH-developed fatigue survey that includes 8 items that asks the participant about fatigue experience and impact over the past 7 days. Each item will be scored on a 5-point Likert scale (1=never/not at all to 5=almost always/very much). Raw scores (range: 8-40) will be converted into standardized T scores (range: 34.1-80.9), with higher scores indicating greater fatigue severity.
Outcome Time Frame
Baseline to end of study (up to approximately 5 years)
Outcome Measure
Change From Baseline at Each Scheduled Assessment in Individual Questions and the Total Fatigue T-score Based on PROMIS Fatigue SF 8a
Outcome Description
The PROMIS Fatigue SF 8a T-score was obtained via the IRT response-pattern scoring approach using the PROMIS Scoring Service available at https://www.assessmentcenter.net/ac\_scoringservice. It is a National Institutes of Health (NIH)-developed fatigue survey of 8 items that asks the participant about fatigue experience and impact over the past 7 days. Each item will be scored on a 5-point Likert scale (1=never/not at all to 5=almost always/very much). Raw scores (range: 8-40) will be converted into standardized T scores (range: 34.1-80.9), with higher scores indicating greater fatigue severity. Moderate or severe symptoms are defined as a baseline PROMIS Fatigue SF 8aT-score \>/= 58.8. A negative change from baseline indicates an improvement.
Outcome Time Frame
Baseline to end of study (up to approximately 5 years)
Outcome Measure
Change From Baseline at Each Scheduled Assessment in Individual Questions and the Total Fatigue T-score Based on PROMIS Fatigue Short Form 8a for Among Participants With Moderate or Severe Symptoms at Baseline
Outcome Description
The MFSAF v4.0 is a questionnaire developed by the PRO Consortium's Myelofibrosis Working Group that focuses on the 7 core symptoms of myelofibrosis: fatigue, night sweats, pruritus, abdominal discomfort, pain under the ribs on the left side, early satiety, and bone pain. It includes 7 items on a 0 (absent) to 10 (worst imaginable) numeric rating scale. A higher score indicates worse symptoms.
Outcome Time Frame
Baseline to end of study (up to approximately 5 years)
Outcome Measure
Change From Baseline at Each Scheduled Assessment in Individual Symptom Score and the Total Score Based on MFSAF v4.0 TSS4
Outcome Description
The MFSAF v4.0 is a questionnaire developed by the PRO Consortium's Myelofibrosis Working Group that focused on the 7 core symptoms of myelofibrosis: fatigue, night sweats, pruritus, abdominal discomfort, pain under the ribs on the left side, early satiety, and bone pain. Items are scored on a 0 (absent) to 10 (worst imaginable) numeric rating scale. The MFSAF TSS4 is the sum of four items in the MFSAF (fatigue, itching \[pruritis\], night sweats, and abdominal discomfort). The weekly TSS4 will be calculated by averaging daily scores over a 7-day interval leading to Week 32 (inclusive). Moderate or severe symptoms are defined as a baseline MFSAF TSS4 \>/=9.1. A higher score indicates worse symptoms. A negative change from baseline indicates an improvement.
Outcome Time Frame
Baseline to end of study (up to approximately 5 years)
Outcome Measure
Change From Baseline at Each Scheduled Assessment in Individual Symptom Score and the MFSAF v4.0 TSS4 Among Participants With Moderate or Severe Symptoms at Baseline
Outcome Description
The PROMIS Fatigue SF 8a T-score will be obtained via the IRT response-pattern scoring approach using the PROMIS Scoring Service available at https://www.assessmentcenter.net/ac\_scoringservice. It is an NIH-developed fatigue survey that includes 8 items that asks the participant about fatigue experience and impact over the past 7 days. Each item will be scored on a 5-point Likert scale (1=never/not at all to 5=almost always/very much). Raw scores (range: 8-40) will be converted into standardized T scores (range: 34.1-80.9), with higher scores indicating greater fatigue severity. A negative change from baseline indicates an improvement.
Outcome Time Frame
At Week 32
Outcome Measure
Part 1a: Percentage of Participants With a Meaningful Within-person Change at Week 32 in the PROMIS Fatigue SF 8a Total T-score
Outcome Description
The MFSAF v4.0 is a questionnaire developed by the PRO Consortium's Myelofibrosis Working Group that focuses on the 7 core symptoms of myelofibrosis: fatigue, night sweats, pruritus, abdominal discomfort, pain under the ribs on the left side, early satiety, and bone pain. It includes 7 items on a 0 (absent) to 10 (worst imaginable) numeric rating scale. The MFSAF TSS4 is the sum of four items in the MFSAF (fatigue, itching \[pruritis\], night sweats, and abdominal discomfort). The weekly TSS4 will be calculated by averaging daily scores over a 7-day interval leading to Week 32 (inclusive).
Outcome Time Frame
At Week 32
Outcome Measure
Part 1a: Percentage of Participants With a Meaningful Within-person Change at Week 32 in the MFSAF TSS4
Outcome Description
MPN-SAF is a 10-item questionnaire measurement tool for symptoms of MPNs. Moderate or severe symptoms are defined as a baseline MPN-SAF problems with concentration ≥ 4. The descriptive analysis approach the distribution of the MPN-SAF problems with concentration at Baseline was categorized using the PGI-S. The response quartiles were used to establish the recommended cut-off points for the MPN-SAF Problems with Concentration corresponding to "none" or "mild" versus "moderate or "severe" categories on the PGI-S.
Outcome Time Frame
At Week 32
Outcome Measure
Part 1a: Percentage of Participants With a Meaningful Within-person Change at Week 32 in the MPN-SAF Problems With Concentration
Outcome Description
MPN-SAF is a 10-item questionnaire measurement tool for symptoms of MPNs. Moderate or severe symptoms are defined as a baseline MPN-SAF problems with concentration ≥ 4. The descriptive analysis approach the distribution of the MPN-SAF problems with concentration at Baseline was categorized using the PGI-S. The response quartiles were used to establish the recommended cut-off points for the MPN-SAF Problems with Concentration corresponding to "none" or "mild" versus "moderate or "severe" categories on the PGI-S.
Outcome Time Frame
Baseline to end of study (up to approximately 5 years)
Outcome Measure
Change From Baseline at Each Scheduled Assessment in Individual Symptom Score and the Total Score Based on MPN-SAF TSS 10
Outcome Description
The PGI-S is a single question to assess the severity of PV symptoms over the last 24 hours prior to dosing. The participant will determine the severity of their PV symptoms on a 4-point scale ranging from "None" (0) to "Severe" (3). A higher score indicates worse symptoms. A negative change from baseline indicates an improvement.
Outcome Time Frame
Baseline to end of study (up to approximately 5 years)
Outcome Measure
Change From Baseline in Patient Global Impression of Severity (PGI-S) at Each Scheduled Assessment
Outcome Description
The PGI-S is a single question to assess the severity of PV symptoms over the last 24 hours prior to dosing. The participant will determine the severity of their PV symptoms on a 4-point scale ranging from "None" (0) to "Severe" (3). A higher score indicates worse symptoms. A negative change from baseline indicates an improvement.
Outcome Time Frame
Baseline to end of study (up to approximately 5 years)
Outcome Measure
Percentage of Participants With at Least One Unit Improvement in the PGI-S From Baseline at Each Scheduled Assessment
Outcome Description
PGI-C is a simple, commonly used instrument to obtain a participant's overall assessment of the impact of treatment on the participant's quality of life. Participants will compare his/her condition from the start of the study on a 5-point scale ranging from "Much better" (1) to "Much worse" (5) at the time of the assessment.
Outcome Time Frame
Baseline to end of study (up to approximately 5 years)
Outcome Measure
Percentage of Participants With a Rating on the Patient Global Impression of Change (PGI-C) of Either "Much Better" or "a Little Better" at Each Scheduled Assessment
Outcome Description
PGI-C is a simple, commonly used instrument to obtain a participant's overall assessment of the impact of treatment on the participant's quality of life. Participants will compare his/her condition from the start of the study on a 5-point scale ranging from "Much better" (1) to "Much worse" (5) at the time of the assessment. A higher score indicates a worse condition.
Outcome Time Frame
Baseline to end of study (up to approximately 5 years)
Outcome Measure
Mean PGI-C at Each Scheduled Assessment
Outcome Description
The MFSAF version 4.0 (v4.0) TSS7 is a questionnaire developed by the Patient-Reported Outcome (PRO) Consortium's Myelofibrosis Working Group that focuses on the 7 core symptoms of myelofibrosis: fatigue, night sweats, pruritus, abdominal discomfort, pain under the ribs on the left side, early satiety, and bone pain. It includes 7 items on a 0 (absent) to 10 (worst imaginable) numeric rating scale. A higher score indicates worse symptoms. A negative change from baseline indicates an improvement.
Outcome Time Frame
Baseline to end of study (up to approximately 5 years)
Outcome Measure
Change From Baseline at Each Scheduled Assessment in Individual Symptom Score and the MFSAF v4.0 Total Symptom Score-7 Items (TSS7)
Outcome Description
The EORTC QLQ-C30 is a validated instrument to obtain a participant's overall assessment of the impact of treatment on the participant's quality of life. It consists of 5 functional scales (physical, role, cognitive, emotional, and social functioning), a global quality of life (QoL) scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (appetite loss, diarrhea, dyspnea, constipation, insomnia, financial impact). For the functional and the global QoL scales, a higher score indicates better health. For the symptom scales, a higher score indicates more symptom burden. The QLQ-C30 summary score is calculated as the mean of the combined 13 QLQ-C30 scale and item scores (excluding global QoL and financial impact), with a higher score indicating a better health related QoL. Raw scores are converted into scale scores ranging from 0 to 100.
Outcome Time Frame
Baseline, Week 32
Outcome Measure
Change From Baseline in the Individual Domain Scores and the Total European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score
Outcome Time Frame
Baseline to end of study (up to approximately 5 years)
Outcome Measure
Median Time to First Hematocrit Equal to or Greater Than 45% After Randomization
Outcome Description
Phlebotomy eligibility was defined as either: 1) A confirmed HCT ≥ 45% that was at least 3% higher than the baseline HCT, where confirmation was defined as 2 consecutive HCT assessments that were ≥ 45% and at least 3% higher than the baseline HCT, or 2) HCT ≥ 48%.
Outcome Time Frame
Baseline to end of study (up to approximately 5 years)
Outcome Measure
Median Time to Phlebotomy-eligible After Randomization
Outcome Time Frame
Baseline to end of study (up to approximately 5 years)
Outcome Measure
Percentage of Participants With at Least One Hematocrit Equal to or Greater Than 48%
Outcome Description
Phlebotomy eligibility was defined as either: 1) A confirmed HCT ≥ 45% that was at least 3% higher than the baseline HCT, where confirmation was defined as 2 consecutive HCT assessments that were ≥ 45% and at least 3% higher than the baseline HCT, or 2) HCT ≥ 48%.
Outcome Time Frame
Baseline to end of study (up to approximately 5 years)
Outcome Measure
Percentage of Participants Who Maintain Absence of Phlebotomy Eligibility
Outcome Time Frame
Baseline to end of study (up to approximately 5 years)
Outcome Measure
Phlebotomy Annualized Rate
Outcome Description
Phlebotomy eligibility was defined as either: 1) A confirmed HCT ≥ 45% that was at least 3% higher than the baseline HCT, where confirmation was defined as 2 consecutive HCT assessments that were ≥ 45% and at least 3% higher than the baseline HCT, or 2) HCT ≥ 48%.
Outcome Time Frame
Baseline to Week 52
Outcome Measure
Parts 1a + 1b: Percentage of Participants Originally Randomized to Rusfertide Achieving Absence of Phlebotomy Eligibility More Than 52 Weeks
Outcome Time Frame
Week 32 to Week 52
Outcome Measure
Part 1b: Median Time to First Hematocrit Equal to or Greater Than 45%
Outcome Time Frame
Week 32 to Week 52
Outcome Measure
Part 1b: Median Time to First Phlebotomy
Outcome Time Frame
Baseline to Week 52
Outcome Measure
Parts 1a + 1b: Percentage of Participants With All Hematocrit Values Less Than 45%
Outcome Description
Phlebotomy eligibility was defined as either: 1) A confirmed HCT ≥ 45% that was at least 3% higher than the baseline HCT, where confirmation was defined as 2 consecutive HCT assessments that were ≥ 45% and at least 3% higher than the baseline HCT, or 2) HCT ≥ 48%.
Outcome Time Frame
Baseline to Week 52
Outcome Measure
Parts 1a + 1b: Percentage of Participants Randomized to Placebo Who Meet the Phlebotomy Eligibility in Part 1a and Part 1b, Separately
Outcome Time Frame
Baseline up to end of study (up to approximately 5 years)
Outcome Measure
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Swati Goel
Investigator Email
swgoel@montefiore.org
Investigator Phone
718-920-6310 / 718-920-4137
Investigator Department
Medicine
Investigator Division
Hematology
Investigator Sponsor Organization
External
Study Department
Medicine
Study Division
Hematology
Categories Mesh Debug
Blood & Bone Marrow Cancers --- HEMATOLOGIC NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
Blood Disorders --- HEMATOLOGIC DISEASES
Blood & Bone Marrow Cancers --- MYELOPROLIFERATIVE DISORDERS
MeSH Terms
POLYCYTHEMIA VERA
BONE MARROW NEOPLASMS
HEMATOLOGIC NEOPLASMS
NEOPLASMS BY SITE
NEOPLASMS
BONE MARROW DISEASES
HEMATOLOGIC DISEASES
HEMIC AND LYMPHATIC DISEASES
MYELOPROLIFERATIVE DISORDERS