Brief Summary
The purpose of this study is to evaluate the effect of two different doses of ianalumab added to eltrombopag to prolong Time to Treatment Failure (TTF) in adults with primary ITP who failed previous first-line treatment with steroids.
Brief Title
A Study of Efficacy and Safety of Ianalumab Versus Placebo in Addition to Eltrombopag in Primary Immune Thrombocytopenia Patients Who Failed Steroids
Detailed Description
This is a multicenter, randomized, double-blinded phase 3 study to assess efficacy and safety of two different doses of ianalumab versus placebo in addition to eltrombopag in adults with primary ITP (platelet count \<30 G/L) who failed previous first-line treatment with corticosteroids.
After completion of the screening period, the participants will enter the randomized treatment period (ianalumab/placebo with eltrombopag) followed by the eltrombopag tapering period. Afterwards, all participants will enter the follow-up period to be monitored for efficacy and safety or safety only depending on how the participants responded to the study treatment.
After completion of the screening period, the participants will enter the randomized treatment period (ianalumab/placebo with eltrombopag) followed by the eltrombopag tapering period. Afterwards, all participants will enter the follow-up period to be monitored for efficacy and safety or safety only depending on how the participants responded to the study treatment.
Completion Date
Completion Date Type
Estimated
Conditions
Primary Immune Thrombocytopenia
Eligibility Criteria
Key Inclusion criteria
1. Male or female patients aged 18 years and older on the day of signing the informed consent.
2. A signed informed consent must be obtained prior to participation in the study.
3. A diagnosis of primary ITP, with insufficient response to, or relapse after a first-line corticosteroid therapy ± IVIG.
4. Patient with platelet count \<30G/L (whom eltrombopag is clinically indicated as per physician's discretion) and with no contraindication to receive eltrombopag
Key Exclusion criteria
1. ITP patients who received second-line ITP treatments (other than steroid therapy± IVIG) including splenectomy. However, patients exposed to thrombopoietin receptor agonists (TPO-RAs) for a limited time (max one week) before screening are eligible.
2. Patients with key lab abnormalities and patients with Evans syndrome or any other cytopenia, (patients with low grade anemia related to bleeding or iron deficiency are eligible).
3. Patients with history of clinically significant hematological disorders, or with marked altered hematologic parameters
4. Patients with current or history of life-threatening bleeding
5. Patient that are Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV), Hepatitis B surface Antigen (HBsAg)/ Hepatitis B core antibody (HBcAb)-positive. HBcAb-positive patients can be enrolled if HBsAg negative, HBV DNA negative, no pre-existing liver fibrosis is present and antiviral prophylaxis is given
6. Patients with known active or uncontrolled infection requiring systemic treatment during screening period
7. Patients with hepatic impairment
8. Patients with concurrent coagulation disorders and/or receiving antiplatelet or anticoagulant medication with an exemption of low dose of acetylsalicylic acid (≤150 mg daily)
9. Nursing (breast feeding) or pregnant women
Other protocol-defined inclusion/exclusion criteria may apply.
1. Male or female patients aged 18 years and older on the day of signing the informed consent.
2. A signed informed consent must be obtained prior to participation in the study.
3. A diagnosis of primary ITP, with insufficient response to, or relapse after a first-line corticosteroid therapy ± IVIG.
4. Patient with platelet count \<30G/L (whom eltrombopag is clinically indicated as per physician's discretion) and with no contraindication to receive eltrombopag
Key Exclusion criteria
1. ITP patients who received second-line ITP treatments (other than steroid therapy± IVIG) including splenectomy. However, patients exposed to thrombopoietin receptor agonists (TPO-RAs) for a limited time (max one week) before screening are eligible.
2. Patients with key lab abnormalities and patients with Evans syndrome or any other cytopenia, (patients with low grade anemia related to bleeding or iron deficiency are eligible).
3. Patients with history of clinically significant hematological disorders, or with marked altered hematologic parameters
4. Patients with current or history of life-threatening bleeding
5. Patient that are Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV), Hepatitis B surface Antigen (HBsAg)/ Hepatitis B core antibody (HBcAb)-positive. HBcAb-positive patients can be enrolled if HBsAg negative, HBV DNA negative, no pre-existing liver fibrosis is present and antiviral prophylaxis is given
6. Patients with known active or uncontrolled infection requiring systemic treatment during screening period
7. Patients with hepatic impairment
8. Patients with concurrent coagulation disorders and/or receiving antiplatelet or anticoagulant medication with an exemption of low dose of acetylsalicylic acid (≤150 mg daily)
9. Nursing (breast feeding) or pregnant women
Other protocol-defined inclusion/exclusion criteria may apply.
Inclusion Criteria
Inclusion criteria
1. Male or female patients aged 18 years and older on the day of signing the informed consent.
2. A signed informed consent must be obtained prior to participation in the study.
3. A diagnosis of primary ITP, with insufficient response to, or relapse after a first-line corticosteroid therapy ± IVIG.
4. Patient with platelet count \<30G/L (whom eltrombopag is clinically indicated as per physician's discretion) and with no contraindication to receive eltrombopag
inclusion/
1. Male or female patients aged 18 years and older on the day of signing the informed consent.
2. A signed informed consent must be obtained prior to participation in the study.
3. A diagnosis of primary ITP, with insufficient response to, or relapse after a first-line corticosteroid therapy ± IVIG.
4. Patient with platelet count \<30G/L (whom eltrombopag is clinically indicated as per physician's discretion) and with no contraindication to receive eltrombopag
inclusion/
Gender
All
Gender Based
false
Keywords
Primary immune thrombocytopenia (ITP),
ianalumab
VAY736
B-cell depletion
B-cell Activating Factor Receptor (BAFF-R) blockade
eltrombopag
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
100 Years
Minimum Age
18 Years
NCT Id
NCT05653219
Org Class
Industry
Org Full Name
Novartis
Org Study Id
CVAY736Q12301
Overall Status
Active, not recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 3 Randomized, Double-blind Study of Ianalumab (VAY736) Versus Placebo in Addition to Eltrombopag in Patients With Primary Immune Thrombocytopenia (ITP) Who Had an Insufficient Response or Relapsed After First Line Steroid Treatment (VAYHIT2)
Primary Outcomes
Outcome Description
Time from randomization until treatment failure is defined as the time from randomization date until the first of the following events indicative of treatment failure:
* platelet count below 30 G/L
* start of a new ITP treatment
* need for a rescue treatment
* ineligibility to taper or inability to discontinue eltrombopag
* death
* platelet count below 30 G/L
* start of a new ITP treatment
* need for a rescue treatment
* ineligibility to taper or inability to discontinue eltrombopag
* death
Outcome Measure
Time from randomization until treatment failure
Outcome Time Frame
Randomization to until end of study (up to 39 months after randomization of last participant)
Secondary Outcomes
Outcome Description
Percentage of participants with any platelet count of at least 100 G/L in the absence of rescue treatment or new ITP treatment
Outcome Time Frame
Randomization to until end of study (up to 39 months after randomization of last participant)
Outcome Measure
Complete Response rate at each timepoint
Outcome Description
Percentage of participants with any platelet count of at least 50 G/L in the absence of rescue treatment or new ITP treatment
Outcome Time Frame
Randomization to until end of study (up to 39 months after randomization of last participant)
Outcome Measure
Response rate at each timepoint
Outcome Description
Percentage of participants with a best response rate of either response or complete response
Outcome Time Frame
Randomization to until end of study (up to 39 months after randomization of last participant)
Outcome Measure
Best response rate across all timepoints
Outcome Description
Time from randomization to date of first response and time from randomization to date of first complete response
Outcome Time Frame
Time from randomization up to the longest observed treatment period duration
Outcome Measure
Time to first response/time to first complete response
Outcome Description
Time from achievement of response to treatment failure Stable response at 6 months
Outcome Time Frame
Randomization to until end of study (up to 39 months after randomization of last participant)
Outcome Measure
Duration of response
Outcome Description
Percentage of participants with at least 3 platelet count collected at month 6 between (study days 121 and 183 and at least 75% of platelet counts qualified as a response
Outcome Time Frame
At 6 months
Outcome Measure
Stable response at 6 months
Outcome Description
Percentage of participants with at least 2 platelet count collected at year 1 between (study days 296 and 379 and at least 66% of platelet counts qualified as a response
Outcome Time Frame
At 1 year
Outcome Measure
Stable response at 1 year
Outcome Description
Time from achievement of complete response to loss of complete response stable response at 1 year period
Outcome Time Frame
Randomization to end of study (up to 39 months after randomization of last participant)
Outcome Measure
Duration of complete response
Outcome Description
Probability to be treatment failure-free (as defined for the primary efficacy endpoint)
Outcome Time Frame
up to week 24
Outcome Measure
Rate of participants who successfully taper and discontinue eltrombopag in each treatment arm
Outcome Description
Percentage of participants reporting bleeding events according to WHO bleeding scale
Outcome Time Frame
Randomization to until end of study (up to 39 months after randomization of last participant)
Outcome Measure
Percentage of participants with bleeding events according to World Health Organization (WHO)
Outcome Description
Number of participants who are in need of rescue treatment in each treatment arm
Outcome Time Frame
Randomization to until end of study (up to 39 months after randomization of last participant)
Outcome Measure
Number of participants receiving rescue treatment
Outcome Description
Percentage of participants who are in need of rescue treatment
Outcome Time Frame
Randomization to until end of study (up to 39 months after randomization of last participant)
Outcome Measure
Percentage of participants receiving rescue treatment
Outcome Description
Post-baseline frequency of CD19+ B-cell counts (percentage within CD45) compared to baseline
Outcome Time Frame
Randomization to until end of study (up to 39 months after randomization of last participant)
Outcome Measure
Change from baseline in the frequency of CD19+ B-cell counts
Outcome Description
Post-baseline absolute number of CD19+ B-cell counts compared to baseline
Outcome Time Frame
Randomization to until end of study (up to 39 months after randomization of last participant)
Outcome Measure
Change from baseline in the absolute number of CD19+ B-cell counts
Outcome Description
The Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form v1.0 Fatigue 13a includes 13 items that assess fatigue in adults.
Outcome Time Frame
From screening (baseline) until end of study (up 39 months after randomization of last participant)
Outcome Measure
Change from baseline on T-score of the PROMIS SF v1.0 Fatigue 13a
Outcome Description
The ITP-PAQ is a 44 item scale for measuring HRQoL in adults with ITP across ten scales: Symptoms, Bother-Physical Health, Fatigue/Sleep, Activity, Fear, Psychological Health, Work, Social Activity, Women´s Reproductive Health, overall QoL. Each item is rated on a Likert type scale. Each scale is scored from 0 to 100. Higher scores represent better HRQoL.
Outcome Time Frame
From screening (baseline) until end of study (up 39 months after randomization of last participant)
Outcome Measure
Change from baseline in ITP PAQ domain scores of symptoms, fatigue, bother (uncomfortable), activity
Outcome Description
Time to B-cell recovery defined as ≥80% of baseline or ≥50 cells/µL
Outcome Time Frame
Randomization to until end of study (up to 39 months after randomization of last participant)
Outcome Measure
Time to first occurence of B-cell recovery defined as ≥80% of baseline ≥50 cells/µL
Outcome Description
Change from baseline in immunoglobulin levels
Outcome Time Frame
Randomization to until end of study (up to 39 months after randomization of last participant)
Outcome Measure
Change from baseline in immunoglobulins
Outcome Description
AUClast: Area under the curve from time zero to the last measurable concentration sampling time (tlast)
Outcome Time Frame
After first dose (pre-dose, EOI, 168, 336 and 504 hours post dose) and after last dose (pre-dose, EOI, 336, 672, 2016, 3360 hours post dose)
Outcome Measure
PK parameters: AUClast
Outcome Description
AUCtau: Area under the curve calculated to the end of a dosing interval (tau)
Outcome Time Frame
After first dose (pre-dose, EOI, 168, 336 and 504 hours post dose) and after last dose (pre-dose, EOI, 336, 672, 2016, 3360 hours post dose)
Outcome Measure
PK parameters: AUCtau
Outcome Description
Maximum (peak) observed plasma, blood, serum or other body fluid drug concentration
Outcome Time Frame
After first dose (pre-dose, EOI, 168, 336 and 504 hours post dose) and after last dose (pre-dose, EOI, 336, 672, 2016, 3360 hours post dose)
Outcome Measure
PK parameters: Cmax
Outcome Description
Time to reach maximum (peak) observed plasma, blood, serum or other body fluid drug concentration
Outcome Time Frame
After first dose (pre-dose, EOI, 168, 336 and 504 hours post dose) and after last dose (pre-dose, EOI, 336, 672, 2016, 3360 hours post dose)
Outcome Measure
PK parameters: Tmax
Outcome Description
Accumulation ratio calculated using AUC values obtained after the last and first dose
Outcome Time Frame
After last dose (pre-dose, EOI, 336, 672, 2016, 3360 hours post dose)
Outcome Measure
PK parameters: Accumulation ratio Racc
Outcome Description
Anti-drug antibodies (ADA) will be evaluated in samples collected from all participants assessing the immunogenicity of ianalumab
Outcome Time Frame
up to week 33
Outcome Measure
Incidence of anti-ianalumab antibodies in serum (ADA assay) over time
Outcome Description
Anti-drug antibodies (ADA) will be evaluated in samples collected from all participants assessing the immunogenicity of ianalumab
Outcome Time Frame
up to week 33
Outcome Measure
Titer of anti-ianalumab antibodies in serum (ADA assay) over time
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)
100
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Irina Murakhovskaya
Investigator Email
imurakho@montefiore.org
Investigator Phone
IMURAKHO