Povetacicept for Autoimmune Hemolytic Anemia

(RUBY-4 Trial)

Recruiting in Palo Alto (17 mi)

+40 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Alpine Immune Sciences, Inc.

Must not be taking: Rituximab, IVIg, Sutimlimab, others

Disqualifiers: Secondary AIHA, CAD, ITP, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing a medication called povetacicept in adults with certain blood disorders where the immune system attacks their own blood cells. The goal is to see if povetacicept is safe and can help improve these conditions. Participants will receive the medication regularly for several months, with an option to extend the treatment for additional months.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop all current medications, but it does require that certain medications be stopped for specific periods before joining. For example, rituximab must be stopped 12 weeks before, and IVIg 4 weeks before. If you're on standard-of-care medications, their doses must be stable for a certain time.

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

Povetacicept is a novel treatment for autoimmune hemolytic anemia, but specific details about its mechanism or administration are not provided in the available research. Existing treatments often involve corticosteroids, rituximab, or immunosuppressive drugs, and Povetacicept may offer a new approach, potentially with a different mechanism or fewer side effects. ^{1 2 3 4 5}

Research Team

Allison Naumovski

Principal Investigator

Alpine Immune Sciences, Inc.

Eligibility Criteria

Adults with autoimmune cytopenias like immune thrombocytopenia, autoimmune hemolytic anemia, and cold agglutinin disease can join. They must have tried at least one or two treatments before without success. Participants should not have had certain recent treatments (like plasmapheresis), a splenectomy, or blood transfusions shortly before the trial starts.

Inclusion Criteria

I have been diagnosed with wAIHA for over 12 weeks, have low hemoglobin, and treatments haven't worked.

I have CAD with anemia and failed at least one treatment.

I have ITP, tried at least 2 treatments without success, and often have very low platelet counts.

Exclusion Criteria

I haven't taken any immune-modifying drugs recently, except for approved COVID-19 treatments.

I haven't had any blood transfusions or similar treatments in the last 2 weeks.

I haven't had plasmapheresis or similar treatments in the last 8 weeks.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive povetacicept approximately every 4 weeks for 6 months

6 months

Extension

Participants may continue to receive povetacicept for an additional 6 months

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Povetacicept (Immunomodulator)

Trial Overview The study is testing povetacicept to see if it's safe and effective for treating autoimmune cytopenias. Participants will receive doses every four weeks for six months, with a chance to continue in a six-month extension period of the treatment.

Participant Groups

Group I: Part 2: Povetacicept Dose A Experimental Treatment 1 Intervention

Based on the findings of Part 1, one or two dose levels may be assessed in Part 2; if two dose levels are assessed participants will be randomized to receive one of the two dose levels of Povetacicept

Group II: Part 1: Povetacicept 240mg Experimental Treatment 1 Intervention

Participants grouped in 3 cohorts by diagnosis will be administered Povetacicept

Who Is Running the Clinical Trial?

Alpine Immune Sciences, Inc.

Lead Sponsor

Trials

9

Recruited

770+

Findings from Research

Abatacept, a CTLA-4 fusion protein, was successfully used in a 54-year-old woman with therapy-refractory autoimmune hemolytic anemia (AIHA), stabilizing her hemoglobin levels after multiple failed treatments.

The combination of abatacept with azathioprine resulted in a significant and lasting increase in hemoglobin levels, suggesting that abatacept can be an effective option for managing refractory AIHA when used alongside other immunosuppressive therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abatacept as salvage therapy for life-threatening refractory autoimmune hemolytic anemia: a case report. Hoffmann, J., Schliesser, G., Neubauer, A.[2023]

Corticosteroids are the first-line treatment for warm autoimmune hemolytic anemia (AIHA), but for cases that do not respond, rituximab is becoming the preferred second-line option, showing effectiveness in about 70-80% of patients.

For cold agglutinin disease, rituximab is now recommended as the first-line treatment, highlighting its growing importance in managing different forms of AIHA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current treatment strategies in autoimmune hemolytic disorders. Barcellini, W.[2022]

A novel treatment strategy using platelet-loaded Vinca alkaloids was tested in four patients with autoimmune hemolytic anemia (AIHA), leading to significant clinical remissions in three patients who had not responded to previous treatments like splenectomy and glucocorticoids.

The treatment resulted in prolonged red blood cell survival and correction of anemia, with remissions lasting up to three years, demonstrating the potential efficacy of this approach for refractory cases of AIHA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of autoimmune hemolytic anemia with Vinca-loaded platelets. Ahn, YS., Harrington, WJ., Byrnes, JJ., et al.[2016]

A case of autoimmune hemolytic anemia (AIHA) associated with livedo reticularis was successfully treated with peripheral blood stem cell transplantation (PBSCT), leading to full remission for 10 years.

After a relapse, the patient was treated with rituximab, an anti-CD20 antibody, and achieved full remission again, highlighting the effectiveness of both PBSCT and rituximab in managing AIHA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Livedo reticularis associated with autoimmune hemolytic anemia: prolonged remission induced by peripheral blood stem cell transplantation relapse after 10 years and restoration of hemoglobin levels by rituximab. Ferreira, E., Feitosa, A., Hamerschlak, N., et al.[2015]

Corticosteroids are the first-line treatment for warm autoimmune hemolytic anemia (AIHA), effective in 70-85% of patients, but require a slow tapering over 6-12 months.

Rituximab is highly effective for refractory cases of warm AIHA (80-90% success) and is now recommended as the first-line treatment for cold agglutinin disease (CAD), suggesting a shift in treatment strategies towards less toxic options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of autoimmune hemolytic anemias. Zanella, A., Barcellini, W.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Abatacept as salvage therapy for life-threatening refractory autoimmune hemolytic anemia: a case report. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Current treatment strategies in autoimmune hemolytic disorders. [2022]

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

Treatment of autoimmune hemolytic anemia with Vinca-loaded platelets. [2016]

4. Brazil pubmed.ncbi.nlm.nih.gov

Livedo reticularis associated with autoimmune hemolytic anemia: prolonged remission induced by peripheral blood stem cell transplantation relapse after 10 years and restoration of hemoglobin levels by rituximab. [2015]

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

Treatment of autoimmune hemolytic anemias. [2022]