M281 for Autoimmune Hemolytic Anemia

(ENERGY Trial)

Recruiting at 154 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

Sponsor: Janssen Research & Development, LLC

Disqualifiers: Pregnancy, Breastfeeding, Cold AIHA, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing a medication called nipocalimab to see if it can help people with a blood disorder called warm autoimmune hemolytic anemia. The medication works by stopping the immune system from destroying red blood cells, which can help reduce anemia symptoms.

Do I have to stop taking my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

How does the drug M281 differ from other treatments for autoimmune hemolytic anemia?

M281, also known as Nipocalimab, is unique because it targets the neonatal Fc receptor, which plays a role in recycling antibodies in the body. This mechanism is different from other treatments that may focus on different pathways or receptors involved in autoimmune hemolytic anemia. ^{1 2 3 4 5}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

Adults over 18 with warm autoimmune hemolytic anemia (wAIHA) who are currently or previously treated for wAIHA can join. Those with cold antibody AIHA, mixed type AIHA, or paroxysmal cold hemoglobinuria cannot participate. Pregnant or breastfeeding individuals and those with other significant health issues are also excluded.

Inclusion Criteria

I am 18 years old or older.

I have been treated for warm autoimmune hemolytic anemia for over 3 months.

Participants must be able to understand and voluntarily provide written informed consent to participate in the study and comply with all study procedures

Exclusion Criteria

Participants must not have other clinically relevant abnormalities currently or in their history that the Investigator would deem them ineligible to participate

I have been diagnosed with a type of anemia caused by cold-reacting antibodies.

Participants must not be pregnant or breastfeeding

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-blind Treatment

Participants receive M281 or placebo every 2 or 4 weeks during the double-blind period

24 weeks

Bi-weekly or monthly visits

Open-label Extension

Participants receive M281 every 2 or 4 weeks during the open-label extension period

144 weeks

Bi-weekly or monthly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Treatment Details

Interventions

• M281 (Monoclonal Antibodies)

Trial Overview The trial is testing the effectiveness and safety of a medication called M281 in adults with wAIHA compared to a placebo. Participants will either receive M281 or a placebo to determine if M281 improves their condition.

Participant Groups

Group I: Placebo administered every 2 weeks (double-blind period) Experimental Treatment 1 Intervention

Participants will receive M281 matching placebo administered every 2 weeks during the 24 weeks double-blind period.

Group II: M281 administered every 4 weeks (open-label extension period) Experimental Treatment 1 Intervention

Participants will receive M281 administered every 4 weeks during the 144 weeks open-label extension period.

Group III: M281 administered every 4 weeks (double-blind period) Experimental Treatment 2 Interventions

Participants will receive M281 administered every 4 weeks alternating with placebo every 4 weeks during the 24 weeks double-blind period.

Group IV: M281 administered every 2 weeks (open-label extension period) Experimental Treatment 1 Intervention

Participants will receive M281 administered every 2 weeks during the 144 weeks open-label extension period.

Group V: M281 administered every 2 weeks (double-blind period) Experimental Treatment 1 Intervention

Participants will receive M281 administered every 2 weeks during the 24 weeks double-blind period.

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

Findings from Research

FcγRIIB plays a crucial regulatory role in preventing autoimmune hemolytic anemia specifically for IgG1 antibodies, as demonstrated by more severe anemia in FcγRIIB-deficient mice compared to those with the receptor after administration of certain IgG1 mAbs.

The study highlights that the galactosylation of IgG1 antibodies is critical for their pathogenic potential and interaction with FcγRs, while sialylation does not have the same effect, indicating that the structure of these antibodies influences their ability to cause disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Galactosylation of IgG1 modulates FcγRIIB-mediated inhibition of murine autoimmune hemolytic anemia. Yamada, K., Ito, K., Furukawa, J., et al.[2013]

The fully human IgG1 kappa antibody MDE-8 effectively blocks the Fc-gamma receptor IIa (FcgammaRIIa), leading to a significant reduction in its expression on immune cells, which could impact immune responses.

In an FcgammaRIIa transgenic mouse model, MDE-8 successfully prevented antibody-induced anemia, demonstrating its potential therapeutic efficacy in conditions involving antibody-mediated clearance of red blood cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel human CD32 mAb blocks experimental immune haemolytic anaemia in FcgammaRIIA transgenic mice. van Royen-Kerkhof, A., Sanders, EA., Walraven, V., et al.[2007]

The study found that low-affinity anti-red blood cell autoantibodies, like the 4C8 IgG2a variant, can be highly pathogenic in inducing anemia, despite having significantly lower binding activity compared to their high-affinity counterparts.

The pathogenicity of these low-affinity antibodies is attributed to their ability to interact with Fc receptors that facilitate the destruction of red blood cells, emphasizing the importance of the antibody's structure over its binding strength in autoimmune hemolytic anemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High pathogenic potential of low-affinity autoantibodies in experimental autoimmune hemolytic anemia. Fossati-Jimack, L., Reininger, L., Chicheportiche, Y., et al.[2019]

Recombinant interleukin-3 (rIL-3) significantly improved survival rates in a lethal model of acute anemia, with over 90% of treated animals recovering, compared to only one-third survival with recombinant erythropoietin (rEpo) and no protection from recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF).

The therapeutic effect of rIL-3 is attributed to its ability to promote the growth of erythroid progenitors and enhance macrophage phagocytosis, which helps eliminate agglutinated red blood cells, thereby addressing both the anemia and associated hemodynamic failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interleukin 3 perfusion prevents death due to acute anemia induced by monoclonal antierythrocyte autoantibody. Shibata, T., Kindler, V., Chicheportiche, Y., et al.[2019]

The study compared various chimaeric antibodies with different human IgG subclasses for their ability to induce antibody-dependent cellular cytotoxicity (ADCC) against NIP-derivatised red blood cells using pre-stimulated U937, HL-60, and K cells.

Results indicate that all three human Fc gamma receptors (Fc gamma R1, Fc gamma R11, and Fc gamma R111) recognize a common binding site on IgG, but each receptor interacts with this site differently, suggesting potential for optimizing antibody design for enhanced therapeutic efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mapping and comparison of the interaction sites on the Fc region of IgG responsible for triggering antibody dependent cellular cytotoxicity (ADCC) through different types of human Fc gamma receptor. Sarmay, G., Lund, J., Rozsnyay, Z., et al.[2019]

References

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

Galactosylation of IgG1 modulates FcγRIIB-mediated inhibition of murine autoimmune hemolytic anemia. [2013]

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

A novel human CD32 mAb blocks experimental immune haemolytic anaemia in FcgammaRIIA transgenic mice. [2007]

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

High pathogenic potential of low-affinity autoantibodies in experimental autoimmune hemolytic anemia. [2019]

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

Interleukin 3 perfusion prevents death due to acute anemia induced by monoclonal antierythrocyte autoantibody. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Mapping and comparison of the interaction sites on the Fc region of IgG responsible for triggering antibody dependent cellular cytotoxicity (ADCC) through different types of human Fc gamma receptor. [2019]