A Study to Assess the Tolerability of Ianalumab (VAY736) With Investigator's Choice Thrombopoietin Receptor Agonist (IC TPO-RA) in Patients With Primary Immune Thrombocytopenia (ITP)

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.
Brief Title
A Study to Assess the Tolerability of Ianalumab (VAY736) With Investigator's Choice Thrombopoietin Receptor Agonist (IC TPO-RA) in Patients With Primary Immune Thrombocytopenia (ITP)
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.
Central Contacts
Central Contact Role
Contact
Central Contact Phone
1-888-669-6682
Central Contact Email
novartis.email@novartis.com
Central Contact Role
Contact
Central Contact Email
novartis.email@novartis.com
Completion Date
Completion Date Type
Estimated
Conditions
PRIMARY IMMUNE THROMBOCYTOPENIA (ITP)
PRIMARY EVANS SYNDROME (ES)
Eligibility 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
Inclusion Criteria
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.

Gender
All
Gender Based
false
Keywords
Immune thrombocytopenia (ITP)
Evans syndrome (ES)
Ianalumab
VAY736
B-cell depletion
B-cell Activating Factor Receptor (BAFF-R)
Healthy Volunteers
No
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT07421167
Org Class
Industry
Org Full Name
Novartis
Org Study Id
CVAY736Q1US01
Overall Status
Recruiting
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Phase 2 Open-label Study to Evaluate the Tolerability of Ianalumab (VAY736) With Investigator's Choice Thrombopoietin Receptor Agonist (IC TPO-RA) in Patients With Primary Immune Thrombocytopenia (ITP) Previously Treated With at Least One Treatment (VAY2EXPLORE)
Primary Outcomes
Outcome Description
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.
Outcome Measure
(Main cohort: Primary immune thrombocytopenia (ITP)): Percentages of participants who are tolerable to ianalumab (9 mg/kg)
Outcome Time Frame
Up to Week 16
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
From Week 1 Day 1 (first dose of ianalumab) to the end of study (EOS), an average of 4 years
Outcome Measure
(Main cohort: Primary immune thrombocytopenia (ITP)): Incidence rate of Adverse Events
Outcome Description
Platelet count will be measured as part of routine hematology safety assessments
Outcome Time Frame
Baseline, and at each scheduled study visit until the end of study (EOS), an average of 2 years
Outcome Measure
(Main cohort: Primary immune thrombocytopenia (ITP)): Percentage of participants with platelet count ≥ 30 G/L, ≥ 50 G/L, ≥ 100 G/L
Outcome Description
Platelet count will be measured as part of routine hematology safety assessments
Outcome Time Frame
Baseline, and at each scheduled study visit until the end of study (EOS), an average of 2 years
Outcome Measure
(Main cohort: Primary immune thrombocytopenia (ITP)): Change from baseline in platelet count for prespecified subgroups (<30, 30 to 50, 50 to <100 G/L)
Outcome Description
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.
Outcome Time Frame
From Week 17 Day 1 (W17D1) through Week 33 Day 1 (W33D1).
Outcome Measure
(Main cohort: Primary immune thrombocytopenia (ITP)): Percentage of participants with successful IC TPO-RA tapering
Start Date
Start Date Type
Actual
Status Verified Date
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
Irina Murakhovskaya
Investigator Email
imurakho@montefiore.org
Investigator Phone
IMURAKHO
Investigator Department
Medicine
Investigator Division
Hematology
Investigator Sponsor Organization
External
Study Department
Medicine
Study Division
Hematology
Categories Mesh Debug
Blood Disorders --- BLOOD COAGULATION DISORDERS
Blood Disorders --- HEMATOLOGIC DISEASES
Blood Disorders --- BLOOD PLATELET DISORDERS
Immune System --- IMMUNE SYSTEM DISEASES
Blood Disorders --- HEMORRHAGE
MeSH Terms
PURPURA, THROMBOCYTOPENIC, IDIOPATHIC
EVANS SYNDROME
PURPURA, THROMBOCYTOPENIC
PURPURA
BLOOD COAGULATION DISORDERS
HEMATOLOGIC DISEASES
HEMIC AND LYMPHATIC DISEASES
THROMBOTIC MICROANGIOPATHIES
THROMBOCYTOPENIA
BLOOD PLATELET DISORDERS
CYTOPENIA
HEMORRHAGIC DISORDERS
AUTOIMMUNE DISEASES
IMMUNE SYSTEM DISEASES
HEMORRHAGE
PATHOLOGIC PROCESSES
PATHOLOGICAL CONDITIONS, SIGNS AND SYMPTOMS
SKIN MANIFESTATIONS
SIGNS AND SYMPTOMS
IANALUMAB
ELTROMBOPAG
AVATROMBOPAG
ROMIPLOSTIM