Ianalumab for Autoimmune Hemolytic Anemia

(VAYHIA Trial)

Recruiting at 75 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Must not be taking: B-cell depleting therapy

Disqualifiers: Hematologic disease, Other AIHA, Infections, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 22

Duration: 25 weeks

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ianalumab for individuals with warm autoimmune hemolytic anemia (wAIHA), a condition where the immune system attacks and destroys red blood cells, leading to anemia. The trial aims to evaluate the effectiveness and safety of ianalumab compared to a placebo (a substance with no active drug). Participants are divided into two groups receiving different doses of ianalumab and one group receiving a placebo. The trial seeks participants with wAIHA who have experienced symptoms like fatigue due to low hemoglobin levels and have not improved with previous treatments. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially bringing a new treatment to market.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, your supportive care dose must be stable for at least 4 weeks before joining the study, and certain medications may be prohibited if they are related to other immunologic diseases.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ianalumab has been tested for safety in conditions similar to autoimmune hemolytic anemia. Specifically, studies have found that ianalumab can help maintain safe platelet levels in patients with primary immune thrombocytopenia (ITP). Patients in these studies tolerated the treatment well, with no serious safety issues reported.

Since this trial is in a later stage, ianalumab has demonstrated promising safety results in earlier studies. By this point, treatments typically have a history of being safe for humans. While specific safety data for autoimmune hemolytic anemia is not yet available, existing research on ianalumab provides some reassurance about its overall safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for autoimmune hemolytic anemia?

Researchers are excited about Ianalumab for autoimmune hemolytic anemia because it offers a fresh approach by targeting the immune system in a novel way. Most current treatments, like corticosteroids and immunosuppressants, work by broadly dampening the immune response. However, Ianalumab is a monoclonal antibody that specifically targets the BAFF receptor, which plays a key role in the survival of B cells responsible for the condition. This targeted action could potentially lead to better outcomes with fewer side effects compared to existing options.

What evidence suggests that ianalumab might be an effective treatment for autoimmune hemolytic anemia?

Research shows that ianalumab may help treat conditions like warm autoimmune hemolytic anemia (wAIHA). In earlier studies, ianalumab successfully lowered disease activity in similar autoimmune conditions, such as Sjögren's disease. This suggests it might help wAIHA by targeting the immune system to stop the destruction of red blood cells. Some early signs indicate that it could improve symptoms for patients who haven't responded to other treatments. In this trial, participants will receive either a low or high dose of ianalumab, or a placebo, to further investigate its potential benefits for wAIHA. However, more research is needed to fully understand its potential benefits for wAIHA. ^{1 2 3 5 6}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for adults with warm autoimmune hemolytic anemia (wAIHA) who haven't had success with at least one previous treatment. They should have symptoms related to anemia and a hemoglobin level below 10 g/dL. Participants must not have changed their supportive care dose in the last four weeks.

Inclusion Criteria

My hemoglobin is below 10 g/dL and I feel tired or weak.

My supportive care medication dose has been stable for at least 4 weeks.

My hemoglobin levels are between 5 and 10 g/dL, and I feel symptoms of anemia.

Exclusion Criteria

My kidney function is normal; my creatinine is not more than 1.5 times the normal limit.

I have a type of anemia or low blood cell counts not caused by iron deficiency.

I haven't used B-cell depleting therapy like rituximab in the last 12 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive randomized treatment with ianalumab or placebo, with visits every other week

25 weeks

Bi-weekly visits (in-person)

Efficacy and Safety Follow-up

Participants are monitored for efficacy and safety, with monthly visits for the first 20 weeks and quarterly visits thereafter

Up to 2 years

Monthly visits (in-person) for 20 weeks, then quarterly

Open-label Extension

Participants in the placebo group not responding to treatment may receive open-label ianalumab

Long-term Follow-up

Participants with a durable response are monitored monthly for efficacy for the first 2 years, then quarterly until loss of response or end of study

Up to 39 months post-randomization

Monthly visits (in-person) for 2 years, then quarterly

What Are the Treatments Tested in This Trial?

Interventions

• Ianalumab
• Placebo

Trial Overview The study is testing Ianalumab against a placebo in patients with wAIHA who didn't respond well to past treatments. The goal is to see if Ianalumab is more effective and safe compared to not receiving the active drug.

How Is the Trial Designed?

Group I: Ianalumab low dose Experimental Treatment 1 Intervention

Participants will receive low dose ianalumab intravenously

Group II: Ianalumab high dose Experimental Treatment 1 Intervention

Participants will receive high dose ianalumab intravenously

Group III: Placebo Placebo Group 1 Intervention

Participants will receive placebo intravenously

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

In a study involving 11 patients with chronic warm antibody type autoimmune hemolytic anemia (AIHA) and 6 patients with chronic idiopathic thrombocytopenia (ITP), rituximab therapy resulted in a 64% overall response rate for AIHA and an 83% response rate for ITP.

Responses to rituximab were more sustained in AIHA patients with underlying lymphoproliferative disorders when combined with chemotherapy, while responses in ITP tended to be transient.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab in the treatment of refractory autoimmune cytopenias in adults. Narat, S., Gandla, J., Hoffbrand, AV., et al.[2015]

Corticosteroids are the first-line treatment for warm autoimmune hemolytic anemia (AIHA), while rituximab is becoming the preferred second-line treatment, showing effectiveness in about 70%-80% of cases.

Rituximab is now recommended as the first-line treatment for cold agglutinin disease (CAD), highlighting a shift towards targeted therapies in managing these autoimmune conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune Hemolysis: Diagnosis and Treatment Recommendations. Barcellini, W.[2018]

In a case study of a 63-year-old woman with Waldenström macroglobulinemia (WM) and immune thrombocytopenia (ITP), treatment with ibrutinib effectively corrected her severe thrombocytopenia within five days, demonstrating its efficacy in managing WM-related complications.

The patient developed warm autoimmune hemolytic anemia (AIHA) likely induced by eltrombopag, highlighting the importance of monitoring for drug-induced hemolysis in patients with WM undergoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First Report of Severe Autoimmune Hemolytic Anemia During Eltrombopag Therapy in Waldenström Macroglobulinemia-Associated Thrombocytopenia. Shen, Y., Yu, F., Ge, H., et al.[2021]

In a study of 101 patients with warm-type autoimmune hemolytic anemia (AIHA), 96% responded positively to steroid treatment, indicating high initial efficacy, regardless of whether the AIHA was primary or secondary.

The overall survival rate was 84% over a median follow-up of 53 months, with age over 50 and the presence of malignancy identified as independent risk factors for lower survival, highlighting the importance of careful management to avoid complications like sepsis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical characteristics and long-term outcomes of warm-type autoimmune hemolytic anemia. Rattarittamrong, E., Eiamprapai, P., Tantiworawit, A., et al.[2022]

The study found that anemia caused by GPA-specific antibodies in autoimmune hemolytic anemia (AHA) occurs through a mechanism of red blood cell (RBC) agglutination, rather than the traditional Fcγ receptor-mediated processes, indicating a different underlying cause for the condition.

Intravenous immune globulin (IVIG) treatment did not significantly impact the anemia induced by the GPA-specific antibody, suggesting that the mechanism of anemia should be considered when evaluating the effectiveness of IVIG therapy in AHA patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibody specific for the glycophorin A complex mediates intravenous immune globulin-resistant anemia in a murine model. Chen, X., Ghaffar, H., Jen, CC., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05648968

NCT05648968 | A Study of Efficacy and Safety ... The purpose of this study is to evaluate efficacy and safety of ianalumab compared to placebo in patients with warm autoimmune hemolytic anemia.

2. novartis.com novartis.com/clinicaltrials/study/nct05648968

A Study of Efficacy and Safety of Ianalumab in Previously ... The purpose of this study is to evaluate efficacy and safety of ianalumab compared to placebo in patients with warm autoimmune hemolytic anemia, who failed at ...

3. novartis.com novartis.com/news/media-releases/novartis-ianalumab-first-drug-reduce-disease-activity-and-patient-burden-sjogrens-disease-phase-iii-trials

Novartis ianalumab first drug to reduce disease activity and ... These trials were designed to provide comprehensive data on the potential of ianalumab as a targeted treatment for Sjögren's disease, in ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10428764/

VAYHIA: A RANDOMIZED, DOUBLE-BLIND, PHASE ... The aim of VAYHIA is to assess the efficacy and safety of ianalumab compared with placebo in patients (pts) with wAIHA that has failed ≥1 lines of treatment.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT07039422

NCT07039422 | Study of Ianalumab in Adults With Primary ... This is a multicenter, Phase 2 exploratory study to assess the efficacy and safety of a second course of ianalumab in adults with ITP and wAIHA who have ...

6. novartis.com novartis.com/news/media-releases/novartis-ianalumab-phase-iii-trial-meets-primary-endpoint-itp-demonstrating-statistically-significant-improvement-time-treatment-failure

Novartis ianalumab Phase III trial meets primary endpoint ... Ianalumab prolonged the duration of safe platelet levels during and after treatment in patients with primary immune thrombocytopenia (ITP) ...