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

Phase 2Active Not RecruitingNCT05885555

Novartis Pharmaceuticals41 enrolled

Overview

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.

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 trial includes an option to offer a second course of ianalumab treatment to participants who achieved confirmed response during the initial course of ianalumab and later lost response to explore the benefit of the second course of treatment. The study will end once all participants have completed 24 months of safety follow-up since their last dose of ianalumab (including the optional second course of ianalumab treatment),or discontinued the study earlier.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Primary Immune Thrombocytopenia (ITP)

Interventions

IanalumabBIOLOGICAL

Intravenous infusion, prepared from concentrate solution

Eligibility

Sex: ALLMin age: 18 YearsMax age: 100 Years

Medical Language ↔ Plain English

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. * Prior response to IVIG/anti-D or a corticosteroid (platelet count ≥50 G/L) 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. * Participants with the following conditions at screening: * Neutrophils \<1000/mm3. * Immunoglobulin G (IgG) \<5 g/L * 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.

Locations (24)

Massachusetts General Hospital

Boston, Massachusetts, United States

Outcomes

Primary Outcomes

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 immune thrombocytopenia (ITP) treatment before reaching a confirmed response.

Time frame: Between Week 1 Day 1 and Week 25 Day 1

Secondary Outcomes

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.

Time frame: 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).

Time frame: 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.

Time frame: 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.

Data from ClinicalTrials.gov

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Beth Israel Deaconess Med Center

Boston, Massachusetts, United States

Novartis Investigative Site

CABA, Argentina

Novartis Investigative Site

Garran, Australian Capital Territory, Australia

Novartis Investigative Site

Melbourne, Victoria, Australia

Novartis Investigative Site

Wuhan, Hubei, China

Novartis Investigative Site

Beijing, China

Novartis Investigative Site

Jinan, China

Novartis Investigative Site

Toulouse, France

Novartis Investigative Site

Dresden, Saxony, Germany

...and 14 more locations

Time frame: 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.

Time frame: 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.

Time frame: At 1 year

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.

Time frame: 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.

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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.

Time frame: 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)

Ianalumab serum PK: AUC concentrations over time

Ianalumab concentration in serum over time, including end of infusion and concentration at trough.

Time frame: 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)

Ianalumab serum PK parameters: Cmax

Maximum (peak) observed plasma, blood, serum or other body fluid drug concentration

Time frame: 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)

Ianalumab serum PK parameters: Tmax

Time to reach maximum (peak) observed plasma, blood, serum or other body fluid drug concentration

Time frame: 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)

Confirmed response (CR) in the second course

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.

Time frame: Second course Week 1 Day1 to second course Week 25 Day1

Time to confirmed response in the second course

two (or more) platelet assessments meeting the criteria of a confirmed response.

Time frame: Second course Week 1 Day 1 to second course Week 25 Day 1

Duration of confirmed response in the second course

Time from the first assessment, in the second course 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).

Time frame: Second course Week 1 Day 1 to second course Week 25 Day 1

Response in the second course

Percentage of participants with a platelet count of at least 50 G/L in the absence of rescue treatment/new ITP treatment.

Time frame: Second course Week 1 Day 1 to second course Week 25 Day 1

Complete Response in the second course

Percentage of participants with a platelet count of at least 100 G/L in the absence of rescue treatment/new ITP treatment.

Time frame: Second course Week 1 Day 1 to second course Week 25 Day 1

Bleeding events in the second course according to the Modified World Health Organization (WHO) bleeding scale

Time frame: Second course Week 1 Day 1 to second course Week 25 Day 1

Percentage of participants with bleeding events in the retreatment/second courseaccording to the Modified World Health Organization (WHO) bleeding scale

Time frame: Second course Week 1 Day 1 to second course Week 25 Day 1

Number of Participants who received rescue treatment after second course

Number of participants who required rescue treatment

Time frame: Second course Week 1 Day 1 to second course Week 25 Day 1

Percentage of participants who received rescue treatment after receiving second course

Percentage of participants who required rescue treatment

Time frame: Second course Week 1 Day 1 to second course Week 25 Day 1

Titer of anti-ianalumab antibodies in serum (ADA assay) over time for second course

Anti-drug antibodies (ADA) will be evaluated in samples collected from all participants to assess the immunogenicity of ianalumab

Time frame: Second course Week 1 Day 1 until 20 weeks after last dose of ianalumab

Change from start of second course in immunoglobulins

Post-baseline immunoglobulin levels (change in titers of Total Ig, IgG, IgM, IgA) compared to retreatment baseline

Time frame: From second course 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 start of second course in the absolute number of CD19+ B-cell counts

Post-baseline absolute number of CD19+ B-cell counts compared to baseline

Time frame: From second course 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 start of second course to end of study in the absolute number of CD19+ B-cell counts

Post-baseline absolute number of CD19+ B-cell counts compared to baseline

Time frame: From second course 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

Time frame: From second course 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)

Ianalumab serum concentrations over time in the second course

Ianalumab concentration in serum over time, including end of infusion and concentration at trough.

Time frame: 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) in the second course