Povetacicept for Autoimmune Hemolytic Anemia

(RUBY-4 Trial)

Not currently recruiting at 49 trial locations

Overseen By Sarah Murphy

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Alpine Immune Sciences, Inc.

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

Disqualifiers: Secondary AIHA, CAD, ITP, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called povetacicept for individuals with certain autoimmune blood disorders. Researchers aim to determine if povetacicept is safe and effective for treating immune thrombocytopenia (a condition where the immune system attacks platelets), autoimmune hemolytic anemia (where red blood cells are destroyed), and cold agglutinin disease (another type of red blood cell disorder). Participants will receive the treatment every four weeks for six months. Ideal candidates have struggled with these conditions for at least 12 weeks and have tried multiple treatments without success. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that povetacicept is likely to be safe for humans?

Research has shown that povetacicept has been tested in healthy adults and was generally well-tolerated. In one study, participants received single doses up to 960 mg without major safety issues. These findings suggest that povetacicept might be safe for further testing in people with autoimmune conditions. Although no treatment is without risks, the initial safety results for povetacicept are encouraging for those considering participation in a clinical trial. ^{1 2 3 4 5}

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

Povetacicept is unique because it introduces a novel approach to treating Autoimmune Hemolytic Anemia by targeting specific pathways involved in the disease's progression. Unlike traditional treatments like corticosteroids or immunosuppressants, Povetacicept works by modulating the immune response, potentially offering a more focused and effective solution with fewer side effects. Researchers are excited about this treatment because it may provide a new option for patients who do not respond well to existing therapies, offering hope for improved outcomes and a better quality of life.

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

Research has shown that povetacicept may help treat autoimmune hemolytic anemia. In studies, povetacicept successfully reduced harmful antibodies and certain immune cells involved in autoimmune diseases. The treatment also helped control levels of LDH, a substance in the blood often elevated in these conditions. In this trial, participants will receive povetacicept, with some receiving a 240mg dose in Part 1, while others may receive one of two dose levels in Part 2. These findings suggest that povetacicept might lower inflammation and the production of harmful antibodies, common in autoimmune hemolytic anemia. Overall, early results are promising for its potential effectiveness. ^{1 2 3 5 6}

Who Is on the Research Team?

Allison Naumovski

Principal Investigator

Alpine Immune Sciences, Inc.

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Povetacicept

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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), 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]

Citations

1. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/6462/504845/Povetacicept-ALPN-303-a-Potent-Dual-BAFF-APRIL

Povetacicept (ALPN-303), a Potent Dual BAFF/APRIL ... Conclusions: Povetacicept effectively reduced pathogenic autoantibodies and key B cell populations (e.g., ASC) and limited serum LDH elevations ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S000649712313059X

Povetacicept (ALPN-303), a Potent Dual BAFF/APRIL ... These data suggest that povetacicept may reduce multiple pathogenic inflammatory processes including autoantibody production and may be an effective treatment ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05757570

NCT05757570 | An Open-label Study of Povetacicept in ... The goal of this clinical study is to evaluate povetacicept in adults with autoimmune cytopenias of immune thrombocytopenia, autoimmune hemolytic anemia, and ...

4. journals.lww.com journals.lww.com/hemasphere/fulltext/2023/08003/pb2554__design_of_a_phase_1b_open_label_study_to.2402.aspx

design of a phase 1b open-label study to assess the safety, ... Povetacicept (ALPN-303) is an engineered dual BAFF/APRIL antagonist with the potential to improve outcomes for patients with autoimmune cytopenias. In a mouse ...

5. rarediseaseadvisor.com rarediseaseadvisor.com/news/new-study-assess-povetacicept-adults-cad-other-cytopenias/

New Study to Assess Povetacicept in CAD and Other ... Results from a phase 1 study of povetacicept (RUBY-1) in healthy volunteers showed it was well tolerated at doses up to 960 mg when administered ...

6. ascpt.onlinelibrary.wiley.com ascpt.onlinelibrary.wiley.com/doi/abs/10.1111/cts.70055

A first‐in‐human, randomized study of the safety ... In this first-in-human study in healthy adults, povetacicept was well-tolerated as single ascending doses of up to 960 mg administered intravenously or ...