A Study of Ianalumab (VAY736) in Patients With Primary Immune Thrombocytopenia (ITP) Previously Treated With at Least Two Lines of Therapies

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the therapeutic efficacy, safety and tolerability of ianalumab in adult patients with primary ITP previously treated with at least one corticosteroid and one TPO-RA.

Detailed Description
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This is a phase 2, open-label, single-arm study to evaluate the efficacy, safety and tolerability of ianalumab in participants with primary ITP (platelet count <30 G/L at screening) previously treated with at least a corticosteroid and a TPO-RA. The study consists of the screening period, the primary endpoint assessment period, the follow-up period. The screening period will last for up to 14 days prior to the first dose of ianalumab. All eligible participants will be treated with the same dose of ianalumab and will complete the primary endpoint assessment period. After completion of the primary endpoint assessment period, all participants will continue in safety monitoring and those with a platelet count ≥30 G/L in absence of a new line of ITP therapy and rescue therapy will also continue in efficacy monitoring. The study will end once all participants have completed 24 months of safety follow-up since their last dose of ianalumab or discontinued the study earlier.

Official Title
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A Phase 2 Study to Evaluate the Efficacy and Safety of Ianalumab (VAY736) in Patients With Primary Immune Thrombocytopenia (ITP) Previously Treated With at Least a Corticosteroid and a Thrombopoietin Receptor Agonist (TPO-RA)

Conditions
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Primary Immune Thrombocytopenia (ITP)

Intervention / Treatment
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* Biological: Ianalumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent obtained prior to participation in the study. Male or female participants aged 18 years and older on the day of signing informed consent. Confirmed diagnosis of primary ITP. Prior treatment with at least a corticosteroid (±IVIG) and a TPO-RA: Prior additional therapies are allowed; the corticosteroid or the TPO-RA do not need to be the last treatment. Documented response to IVIG/anti-D or a corticosteroid that was not maintained. At last ITP treatment, loss of response, insufficient response, no response or intolerance. Platelet count <30 G/L and assessed as needing treatment (per physician's discretion) at screening. If concomitant ITP medication is clinically indicated, the platelet assessment showing a value <30 G/L must be performed after at least 14 days on a stable dose of a corticosteroid or/and a TPO-RA (less than 10% variation from current dose) and continue stable thereafter. Key exclusion criteria: Diagnosis of secondary thrombocytopenia. Platelet or whole blood transfusion, plasmapheresis, or use of any other rescue medications within 14 days before first ianalumab infusion. Neutrophils <1000/mm3 at screening. Treatment with a B-cell depleting therapy (e.g., rituximab) or anti-B-cell Activating Factor of the TNF Family (BAFF) (e.g., belimumab) within 12 weeks prior to the first administration of ianalumab. Immunosuppressant drugs other than corticosteroids within 5 times the elimination half-life of the drug or 14 days before first ianalumab infusion, whichever is longer. Prior splenectomy. Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single-arm<br>All eligible participants will receive ianalumab at the same dose. | Biological: Ianalumab<br>* Intravenous infusion, prepared from concentrate solution<br>* Other names: VAY736;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Confirmed response | Confirmed response is defined as a platelet count of equal or above 50 G/L at two (or more) consecutive assessments at least 7 days apart, in the absence of: Rescue treatment for ≥4 weeks prior to the assessment of the platelet count, and New ITP treatment before reaching a confirmed response. | Between Week 1 Day 1 and Week 25 Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to confirmed response | Time from the first administration of ianalumab to the first assessment in the first sequence of two (or more) platelet assessments meeting the criteria of a confirmed response as defined by the primary endpoint. | From Week 1 Day 1 to Week 25 Day 1 | 
| Duration of confirmed response | Time from the first assessment in the first sequence of two (or more) platelet assessments meeting the criteria of a confirmed response to loss of response; with loss of response defined as the first of the following events: platelet count <30 G/L, start of any rescue or new ITP treatment, death (whatever the cause). | From Week 1 Day 1 to end of study (until all participants have completed 24 months of safety follow-up since their last dose of ianalumab or discontinued the study earlier) | 
| Complete Response rate at each timepoint | Percentage of participants with a platelet count of at least 100 G/L in the absence of rescue treatment/new ITP treatment. | From Week 1 Day 1 to end of study (until all participants have completed 24 months of safety follow-up since their last dose of ianalumab or discontinued the study earlier) | 
| Response rate at each timepoint | Percentage of participants with a platelet count of at least 50 G/L in the absence of rescue treatment/new ITP treatment. | From Week 1 Day 1 to end of study (until all participants have completed 24 months of safety follow-up since their last dose of ianalumab or discontinued the study earlier) | 
| Stable response at 6 months | Percentage of participants with at least 75% of platelet counts collected at month 6 (between study days 121 and 183) equal to or above 50 G/L in the absence of rescue treatment/new ITP treatment. | At 6 months | 
| Stable response at 1 year | Percentage of participants with at least 66% of platelet counts collected at year 1 (between study days 296 and 379) equal to or above 50 G/L in the absence of rescue treatment/new ITP treatment. | At 1 year | 
| Number of participants with bleeding events according to the Modified World Health Organization (WHO) bleeding scale | Number of participants reporting bleeding events for each grade of the World Health Organization (WHO) bleeding scale at each time point. Severity is graded from 0 to 4, with 0 = no bleeding and 4 = severe hemodynamic instability/central nervous system (CNS) bleeding/fatal. | From Week 1 Day 1 to end of study (until all participants have completed 24 months of safety follow-up since their last dose of ianalumab or discontinued the study earlier) | 
| Percentage of participants with bleeding events according to the Modified World Health Organization (WHO) bleeding scale | Percentage of participants reporting bleeding events for each grade of the WHO bleeding scale at each time point. Severity is graded from 0 to 4, with 0 = no bleeding and 4 = severe hemodynamic instability/central nervous system (CNS) bleeding/fatal. | From Week 1 Day 1 to end of study (until all participants have completed 24 months of safety follow-up since their last dose of ianalumab or discontinued the study earlier) | 
| Number of participants who received rescue treatment | Number of participants who required rescue treatment | From Week 1 Day 1 to end of study (until all participants have completed 24 months of safety follow-up since their last dose of ianalumab or discontinued the study earlier) | 
| Percentage of participants who received rescue treatment | Percentage of participants who required rescue treatment | From Week 1 Day 1 to end of study (until all participants have completed 24 months of safety follow-up since their last dose of ianalumab or discontinued the study earlier) | 
| Change from baseline in the frequency of CD19+ B-cell counts | Post-baseline frequency of CD19+ B-cell counts compared to baseline | From Week 1 Day 1 to end of study (until all participants have completed 24 months of safety follow-up since their last dose of ianalumab or discontinued the study earlier) | 
| Change from baseline in the absolute number of CD19+ B-cell counts | Post-baseline absolute number of CD19+ B-cell counts compared to baseline | From Week 1 Day 1 to end of study (until all participants have completed 24 months of safety follow-up since their last dose of ianalumab or discontinued the study earlier) | 
| Time to first occurrence of B-cell recovery defined as ≥80% of baseline ≥50 cells/µL | Time to B-cell recovery defined as ≥80% of baseline or ≥50 cells/µL | From Week 1 Day 1 to end of study (until all participants have completed 24 months of safety follow-up since their last dose of ianalumab or discontinued the study earlier) | 
| Change from baseline in immunoglobulins | Post-baseline immunoglobulin levels (change in titers of Total Ig, IgG, IgM, IgA) compared to baseline | From Week 1 Day 1 to end of study (until all participants have completed 24 months of safety follow-up since their last dose of ianalumab or discontinued the study earlier) | 
| Incidence of anti-ianalumab antibodies in serum (ADA assay) over time | Anti-drug antibodies (ADA) will be evaluated in samples collected from all participants to assess the immunogenicity of ianalumab | Up to 20 weeks after last dose of ianalumab | 
| Titer of anti-ianalumab antibodies in serum (ADA assay) over time | Anti-drug antibodies (ADA) will be evaluated in samples collected from all participants to assess the immunogenicity of ianalumab | Up to 20 weeks after last dose of ianalumab | 
| Ianalumab serum concentrations over time | Ianalumab concentration in serum over time, including end of infusion and concentration at trough. | First dose (pre-dose, 2, 168, 336, 504, 672 hours post-dose); Subsequent doses (pre-dose and 2 hours post-dose); Last dose (pre-dose, 2 336, 672, 1344, 2016, 3360 hours post-dose) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Primary immune thrombocytopenia (ITP), ianalumab, VAY736, B-cell depletion, B-cell Activating Factor Receptor (BAFF-R) blockade