Primary Immune Thrombocytopenia (ITP), Primary Evans Syndrome (ES)
Conditions
Keywords
Immune thrombocytopenia (ITP), Evans syndrome (ES), Ianalumab, VAY736, B-cell depletion, B-cell Activating Factor Receptor (BAFF-R)
Brief summary
The purpose of this study is to investigate the tolerability of ianalumab (9 mg/kg) with investigator's choice thrombopoietin receptor agonist (IC TPO-RA) in participants diagnosed with primary immune thrombocytopenia (ITP) who have been treated with at least one but no more than four prior treatments, and with no change in IC TPO-RA dose in at least the last 14 days prior to the start of ianalumab.
Detailed description
The study will include an exploratory cohort of participants with primary Evans syndrome (ES) for whom IC TPO-RA therapy is appropriate per investigator's assessment. The study will consist of a 28-day screening period; a 16-week treatment period; an IC TPO-RA tapering period during which all participants will be monitored for 16 weeks. All participants will then continue to be followed for another 60-weeks (15 months) of long-term safety follow-up period.
Interventions
BIOLOGICALianalumab
9 mg per kilogram infusion every 4 weeks (Q4W) for 16 weeks
IC TPO-RAs will be administered according to the respective United States Prescribing Information (USPIs)
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Signed informed consent must be obtained prior to participation in the study. * Patients aged 18 years and older on the day of signing the informed consent. * ITP cohort only: Confirmed diagnosis of primary ITP that has previously responded to corticosteroid treatment or IVIG treatment but the response was not sustained (response is defined as a platelet count ≥ 50 G/L). * ITP cohort only: Received at least one prior treatment for ITP. * ITP cohort only: Patients with a platelet count \< 100 G/L who are receiving a TPO-RA. Patients may already be receiving a TPO-RA or may start a TPO-RA at the time of screening. All patients should be on a stable dose of TPO-RA for at least 14 days prior to first dose of ianalumab. Note: during the screening period, a documented assessment of platelets \< 100 G/L is mandatory for enrollment. For patients who received rescue medication before screening, platelet count results obtained prior to the start of the rescue therapy should be used to assess eligibility if collected within 14 days prior to screening. * ES cohort only: Patients with clinical diagnosis of primary ES with active thrombocytopenia (\< 100 G/L) with warm autoimmune hemolytic anemia (wAIHA) for whom a TPO-RA is appropriate per Investigator. * ES cohort only: Inadequate response to or relapse after treatment with corticosteroid therapy. * ES cohort only: Diagnosis confirmed by current or past positive direct antiglobulin test (DAT) (IgG+, with or without C3+) and evidence of hemolysis. * ES cohort only: any supportive care treatment administered for wAIHA must be stable for at least 4 weeks prior to enrollment. Key
Exclusion criteria
* Patients being treated with TPO-RA for \> 6 months. * Current life-threatening bleeding (related to thrombocytopenia). * Prior splenectomy within 6 months of first administration of ianalumab. * Patients with the following laboratory abnormalities: * Neutrophils: \< 1000/mm3 * Serum creatinine \> 1.5 × upper limit of normal (ULN) * Aspartate aminotransferase (AST) \> 3.0 × ULN * Alanine aminotransferase (ALT) \> 3.0 × ULN * Immunoglobulin G (IgG) \< 5 g/L * ITP cohort only: hemoglobin \< 10 g/L, total bilirubin \> 1.5 × ULN * Patients with significantly compromised liver disease (Child-Pugh 7 to 9) and decompensated liver disease (Child-Pugh 10 to 15). * Treatment with a B-cell depleting therapy (e.g. rituximab or anti-B cell Activating Factor (e.g. belimumab) within 12 weeks prior to the first administration of ianalumab. Patients who are refractory to rituximab will be excluded from this trial, where refractory is defined as: \~ Patients who have not achieved a response (defined as platelet count ≥ 30 G/L and at least doubling from baseline within 12 weeks in the absence of rescue therapy) following completion of a standard course of rituximab * History of hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical classes. * Known history of primary or secondary immunodeficiency, or a positive human immunodeficiency virus (HIV) enzyme-linked immunosorbent assay (ELISA) and Western blot) test result. * Patients exposed to more than 4 prior treatments for ITP. * ITP cohort only: Diagnosis of secondary thrombocytopenia. * ITP cohort: Use of immunosuppressant drugs other than corticosteroids or rituximab. * ES cohort only: Diagnosis of secondary ES. * ES cohort only: Life-threatening hemolysis. * ES cohort only: patients with autoimmune hemolytic anemia other than wAIHA
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| (Main cohort: Primary immune thrombocytopenia (ITP)): Percentages of participants who are tolerable to ianalumab (9 mg/kg) | Up to Week 16 | The proportion of participants who tolerate ianalumab (9 mg/kg) is defined as those who do not experience any of the following events during the combination treatment period (up to Week 16): * Discontinuation due to an adverse event (AE) unrelated to efficacy * Adverse events leading to dose reduction or dose rate reduction * Adverse events resulting in study drug interruption. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| (Main cohort: Primary immune thrombocytopenia (ITP)): Incidence rate of Adverse Events | From Week 1 Day 1 (first dose of ianalumab) to the end of study (EOS), an average of 4 years | The distribution of adverse events will be conducted through the analysis of frequencies for treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs), based on the monitoring of relevant clinical and laboratory safety parameters. |
| (Main cohort: Primary immune thrombocytopenia (ITP)): Percentage of participants with platelet count ≥ 30 G/L, ≥ 50 G/L, ≥ 100 G/L | Baseline, and at each scheduled study visit until the end of study (EOS), an average of 2 years | Platelet count will be measured as part of routine hematology safety assessments |
| (Main cohort: Primary immune thrombocytopenia (ITP)): Change from baseline in platelet count for prespecified subgroups (<30, 30 to 50, 50 to <100 G/L) | Baseline, and at each scheduled study visit until the end of study (EOS), an average of 2 years | Platelet count will be measured as part of routine hematology safety assessments |
| (Main cohort: Primary immune thrombocytopenia (ITP)): Percentage of participants with successful IC TPO-RA tapering | From Week 17 Day 1 (W17D1) through Week 33 Day 1 (W33D1). | Tapering of investigator's choice thrombopoietin receptor agonist (IC TPO-RA) will be evaluated based on the proportion of participants who successfully discontinue IC TPO-RA without requiring rescue therapy or new immune thrombocytopenia (ITP) treatments by the end of the tapering period. A participant is considered successfully tapered if all of the following criteria are met: * Discontinuation of IC TPO-RA before Week 33 Day 1 (W33D1) with at least two consecutive platelet counts ≥ 30 G/L from separate visits. * No use of rescue treatment or initiation of new ITP therapy in the 4 weeks prior to W33D1. |
Countries
United States
Contacts
CONTACTNovartis Pharmaceuticals
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Outcome results
None listed