Ianalumab for Autoimmune Hemolytic Anemia

(VAYHIA Trial)

Recruiting at 90 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

Trial Summary

What is the purpose of this trial?

This trial is testing ianalumab, a new medication, in patients with warm autoimmune hemolytic anemia who haven't responded to other treatments. The goal is to see if ianalumab can help increase and maintain their hemoglobin levels.

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.

How is the drug Ianalumab different from other treatments for autoimmune hemolytic anemia?

Ianalumab is unique because it targets specific immune system components, potentially offering a new approach for patients who do not respond well to traditional treatments like corticosteroids or rituximab. This drug may work differently by focusing on immune pathways not addressed by existing therapies. ^{1 2 3 4 5}

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

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

I am 18 years old or older.

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.

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Antibody specific for the glycophorin A complex mediates intravenous immune globulin-resistant anemia in a murine model. [2019]

2. New Zealand pubmed.ncbi.nlm.nih.gov

First Report of Severe Autoimmune Hemolytic Anemia During Eltrombopag Therapy in Waldenström Macroglobulinemia-Associated Thrombocytopenia. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Clinical characteristics and long-term outcomes of warm-type autoimmune hemolytic anemia. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Immune Hemolysis: Diagnosis and Treatment Recommendations. [2018]

5. Italy pubmed.ncbi.nlm.nih.gov

Rituximab in the treatment of refractory autoimmune cytopenias in adults. [2015]