Ianalumab plus a thrombopoietin receptor agonist for adults with ITP or Evans syndrome

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)

This study will test whether adding ianalumab to a doctor's chosen TPO-RA is tolerable for adults with immune thrombocytopenia (and an exploratory group with Evans syndrome) who have had prior treatments and are on a stable TPO-RA dose.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 164 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Novartis (Industry-sponsored)
• Drugs / interventions: ianalumab, rituximab, belimumab
• Locations: 2 sites (Margate, Florida and 1 other locations)
• Trial ID: NCT07421167 on ClinicalTrials.gov

What this trial studies

Adults with primary immune thrombocytopenia (and an exploratory cohort with primary Evans syndrome) who are on a stable thrombopoietin receptor agonist will receive ianalumab (9 mg/kg) alongside their chosen TPO-RA to record tolerability and safety. The schedule includes a 28-day screening period, a 16-week treatment period, a TPO-RA tapering period with 16 weeks of monitoring, and a 60-week long-term safety follow-up. Participants must have received between one and four prior treatments for ITP and have had no recent change in their TPO-RA dose. The trial is open at selected U.S. clinical sites and is sponsored by Novartis Pharmaceuticals.

Who should consider this trial

Good fit: Adults age 18 and older with primary ITP who have had at least one prior ITP treatment, have previously responded to steroids or IVIG but with loss of response, and are on a stable TPO-RA dose with platelet counts below 100 G/L (with an exploratory cohort for Evans syndrome meeting similar criteria).

Not a fit: Patients not on a stable TPO-RA dose, with platelet counts consistently ≥100 G/L, or with contraindications to B-cell–targeting therapy are unlikely to benefit from this tolerability-focused regimen.

Why it matters

Potential benefit: If tolerable, the combination could allow some patients to achieve more sustained platelet control and reduce reliance on ongoing rescue therapies.

How similar studies have performed: B-cell–targeting therapies such as rituximab have shown benefit in some ITP patients, but combining a BAFF/BAFF-R–directed agent like ianalumab with TPO-RAs is a more recent approach with limited prior clinical data.

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

Where this trial is running

Margate, Florida and 1 other locations

• DH Cancer Research Center LLC — Margate, Florida, United States (Recruiting)
• Hope And Healing Care — Hinsdale, Illinois, United States (Recruiting)

Study contacts

• Study coordinator: Novartis Pharmaceuticals

Conditions Primary Immune Thrombocytopenia; Primary Evans Syndrome; Immune thrombocytopenia; Evans syndrome; Ianalumab; VAY736; B-cell depletion; B-cell Activating Factor Receptor