Brief Summary
This is a Phase 2 randomized, double-blind, placebo-controlled, multicenter study evaluating the efficacy and safety of AK117 or placebo, combined with azacitidine in patients with newly diagnosed higher-risk myelodysplastic syndromes (HR-MDS).
Brief Title
A Study of AK117 in Combination With Azacitidine in Patients With Myelodysplastic Syndromes
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
(+86)18116403289
Central Contact Email
wenting01.li@akesobio.com
Completion Date
Completion Date Type
Estimated
Conditions
Higher-risk Myelodysplastic Syndromes
Eligibility Criteria
Inclusion Criteria:
* Age ≥ 18 years old at the time of enrolment.
* Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2.
* Expected life expectancy ≥ 3 months.
* Newly diagnosed HR-MDS, according to the 2016 World Health Organization (WHO) classification with the presence of \< 20% blasts in bone marrow or peripheral blood; Overall IPSS-R score ≥ 3.5.
* Ability to undergo the study-required bone marrow sample collection procedures.
* Suitable venous access for the study-required blood sampling (i.e., including PK and immunogenicity).
* Female patients of childbearing age must have negative serum pregnancy test results before randomization or per region-specific guidance documented in the informed consent and a negative urine pregnancy test on the day of first dose prior to dosing.
* Female patients of childbearing potential having sex with an unsterilized male partner must agree to use a highly effective method of contraception from the beginning of screening until 180 days after the last dose of the study treatment.
* Unsterilized male patients having sex with a female partner of childbearing potential must agree to use an effective method of contraception from the beginning of screening until 180 days after the last dose of study treatment.
Exclusion Criteria:
* MDS evolving from a pre-existing myeloproliferative neoplasm (MPN), myelodysplastic/myeloproliferative neoplasms (MDS/MPN).
* Prior treatment with Cluster of Differentiation (CD) 47 or Signal-regulatory protein alpha (SIRPα)-targeting agents.
* Concurrently participating in another interventional clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
* Patients who previously diagnosed with another malignancy and have any evidence of residual disease.
* Known allergy to any component of any study drug; known history of severe hypersensitivity to other monoclonal antibodies.
* Patients with any psychiatric or social factor which the investigator deems may interfere with the patient's ability to comply with the requirements of the study.
* Patients with current hypertension with systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg after oral antihypertensive therapy.
* Patients with known cardiopulmonary disease defined as unstable angina, clinically significant arrhythmia, congestive heart failure (New York Heart Association Class III or IV), decompensated cirrhosis, nephrotic syndrome, uncontrolled metabolic disorders.
* Patients who are breastfeeding or plans to breastfeed during the study.
* Other conditions where the investigator considers the patient inappropriate for enrollment.
* Age ≥ 18 years old at the time of enrolment.
* Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2.
* Expected life expectancy ≥ 3 months.
* Newly diagnosed HR-MDS, according to the 2016 World Health Organization (WHO) classification with the presence of \< 20% blasts in bone marrow or peripheral blood; Overall IPSS-R score ≥ 3.5.
* Ability to undergo the study-required bone marrow sample collection procedures.
* Suitable venous access for the study-required blood sampling (i.e., including PK and immunogenicity).
* Female patients of childbearing age must have negative serum pregnancy test results before randomization or per region-specific guidance documented in the informed consent and a negative urine pregnancy test on the day of first dose prior to dosing.
* Female patients of childbearing potential having sex with an unsterilized male partner must agree to use a highly effective method of contraception from the beginning of screening until 180 days after the last dose of the study treatment.
* Unsterilized male patients having sex with a female partner of childbearing potential must agree to use an effective method of contraception from the beginning of screening until 180 days after the last dose of study treatment.
Exclusion Criteria:
* MDS evolving from a pre-existing myeloproliferative neoplasm (MPN), myelodysplastic/myeloproliferative neoplasms (MDS/MPN).
* Prior treatment with Cluster of Differentiation (CD) 47 or Signal-regulatory protein alpha (SIRPα)-targeting agents.
* Concurrently participating in another interventional clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
* Patients who previously diagnosed with another malignancy and have any evidence of residual disease.
* Known allergy to any component of any study drug; known history of severe hypersensitivity to other monoclonal antibodies.
* Patients with any psychiatric or social factor which the investigator deems may interfere with the patient's ability to comply with the requirements of the study.
* Patients with current hypertension with systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg after oral antihypertensive therapy.
* Patients with known cardiopulmonary disease defined as unstable angina, clinically significant arrhythmia, congestive heart failure (New York Heart Association Class III or IV), decompensated cirrhosis, nephrotic syndrome, uncontrolled metabolic disorders.
* Patients who are breastfeeding or plans to breastfeed during the study.
* Other conditions where the investigator considers the patient inappropriate for enrollment.
Inclusion Criteria
Inclusion Criteria:
* Age ≥ 18 years old at the time of enrolment.
* Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2.
* Expected life expectancy ≥ 3 months.
* Newly diagnosed HR-MDS, according to the 2016 World Health Organization (WHO) classification with the presence of \< 20% blasts in bone marrow or peripheral blood; Overall IPSS-R score ≥ 3.5.
* Ability to undergo the study-required bone marrow sample collection procedures.
* Suitable venous access for the study-required blood sampling (i.e., including PK and immunogenicity).
* Female patients of childbearing age must have negative serum pregnancy test results before randomization or per region-specific guidance documented in the informed consent and a negative urine pregnancy test on the day of first dose prior to dosing.
* Female patients of childbearing potential having sex with an unsterilized male partner must agree to use a highly effective method of contraception from the beginning of screening until 180 days after the last dose of the study treatment.
* Unsterilized male patients having sex with a female partner of childbearing potential must agree to use an effective method of contraception from the beginning of screening until 180 days after the last dose of study treatment.
* Age ≥ 18 years old at the time of enrolment.
* Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2.
* Expected life expectancy ≥ 3 months.
* Newly diagnosed HR-MDS, according to the 2016 World Health Organization (WHO) classification with the presence of \< 20% blasts in bone marrow or peripheral blood; Overall IPSS-R score ≥ 3.5.
* Ability to undergo the study-required bone marrow sample collection procedures.
* Suitable venous access for the study-required blood sampling (i.e., including PK and immunogenicity).
* Female patients of childbearing age must have negative serum pregnancy test results before randomization or per region-specific guidance documented in the informed consent and a negative urine pregnancy test on the day of first dose prior to dosing.
* Female patients of childbearing potential having sex with an unsterilized male partner must agree to use a highly effective method of contraception from the beginning of screening until 180 days after the last dose of the study treatment.
* Unsterilized male patients having sex with a female partner of childbearing potential must agree to use an effective method of contraception from the beginning of screening until 180 days after the last dose of study treatment.
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT06196203
Org Class
Industry
Org Full Name
Akeso
Org Study Id
AK117-205
Overall Status
Recruiting
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Randomized, Double-blind, Placebo-controlled, Multicenter Phase 2 Study of AK117/Placebo in Combination With Azacitidine in Patients With Newly Diagnosed Higher-risk Myelodysplastic Syndromes
Primary Outcomes
Outcome Description
CRR is defined as the proportion of subjects with complete remission (CR) per International Working Group (IWG) 2023 criteria
Outcome Measure
Complete remission rate (CRR)
Outcome Time Frame
Up to approximately 2 years
Secondary Outcomes
Outcome Description
The proportion of subjects with recorded response per IWG 2023
Outcome Time Frame
Up to approximately 2 years
Outcome Measure
Overall response rate (ORR)
Outcome Description
Time from the randomization to the first recorded response
Outcome Time Frame
Up to approximately 2 years
Outcome Measure
Time to response (TTR)
Outcome Description
Time from the randomization to the first recorded CR
Outcome Time Frame
Up to approximately 2 years
Outcome Measure
Time to CR (TTCR)
Outcome Description
Time from the first recorded response until disease relapse or progression or death due to any cause, whichever occurs first
Outcome Time Frame
Up to approximately 2 years
Outcome Measure
Duration of response (DoR)
Outcome Description
Time from the first recorded CR until disease relapse or progression or death due to any cause, whichever occurs first
Outcome Time Frame
Up to approximately 2 years
Outcome Measure
Duration of CR (DoCR)
Outcome Description
Time from randomization until transformation to AML or death due to any cause, whichever occurs first
Outcome Time Frame
Up to approximately 2 years
Outcome Measure
Event-free survival (EFS)
Outcome Description
The time from randomization until death due to any cause
Outcome Time Frame
Up to approximately 2 years
Outcome Measure
Overall survival (OS)
Outcome Description
An AE is any untoward medical occurrence in a subject, temporally associated with the use of study treatment, whether or not considered related to the study treatment
Outcome Time Frame
Up to approximately 2 years
Outcome Measure
Number of subjects with adverse events (AEs)
Outcome Description
Serum concentrations of AK117 in individual subjects at different time points after AK117 administration
Outcome Time Frame
Up to approximately 2 years
Outcome Measure
Pharmacokinetic characteristics
Outcome Description
Number of subjects with detectable anti-drug antibodies
Outcome Time Frame
Up to approximately 2 years
Outcome Measure
Anti-drug antibody (ADA)
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
Mendel Goldfinger
Investigator Email
MGOLDFIN@MONTEFIORE.ORG
Investigator Phone
718-920-4826