M281 for Autoimmune Hemolytic Anemia

(ENERGY Trial)

Recruiting at 163 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Janssen Research & Development, LLC

Disqualifiers: Pregnancy, Breastfeeding, Cold AIHA, others

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

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

Compensation: Varies

Number of Visits: Unknown

111 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called M281 (also known as Nipocalimab, a human monoclonal antibody) to evaluate its effectiveness and safety for people with warm autoimmune hemolytic anemia (wAIHA), a condition where the immune system attacks and destroys red blood cells. The trial includes different groups, with some participants receiving M281 every two or four weeks and others receiving a placebo (inactive treatment) for comparison. Eligible participants should have been diagnosed with wAIHA for at least three months and have received some form of treatment for it. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people, offering a chance to contribute to important advancements in wAIHA treatment.

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.

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

Research has shown that M281, also known as nipocalimab, has undergone safety testing in several studies. One study with healthy volunteers found that a single dose was well-tolerated, with no serious side effects reported. This suggests potential safety for people, but further studies are necessary for confirmation.

M281 has also been studied for its ability to reduce harmful antibodies in the body. These antibodies can cause conditions like autoimmune hemolytic anemia, where the immune system attacks red blood cells.

Since this trial is in its middle to late stages, earlier studies have demonstrated reasonable safety in humans. However, new information may emerge as more participants join the trials. Always consult a healthcare provider when considering joining a trial. ^{1 2 3 4 5}

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

Researchers are excited about M281 for autoimmune hemolytic anemia because it targets a part of the immune system in a novel way. Unlike the standard treatments like corticosteroids, which broadly suppress the immune system, M281 specifically binds to the neonatal Fc receptor (FcRn), which plays a role in prolonging the lifespan of antibodies. By interfering with this receptor, M281 reduces the levels of harmful antibodies that attack red blood cells, potentially offering more precise and effective treatment with fewer side effects. Additionally, this targeted approach could mean better management of symptoms and improved quality of life for patients.

What evidence suggests that M281 might be an effective treatment for autoimmune hemolytic anemia?

Studies have shown that M281, also known as nipocalimab, may help treat warm autoimmune hemolytic anemia (wAIHA) by reducing harmful antibodies called IgG. These antibodies can mistakenly attack the body's own red blood cells, leading to anemia. Research indicates that M281 lowers these antibodies, improving symptoms and overall blood health. In earlier studies, patients taking M281 showed promising improvements in their condition. This trial will administer M281 in different dosing schedules, either every 2 weeks or every 4 weeks, to evaluate its effectiveness. M281 attaches to a specific part of the immune system, decreasing the levels of IgG antibodies, including those causing the disease. Overall, initial findings suggest that M281 could be an effective treatment option for people with wAIHA. ^{2 3 4 6 7}

Who Is on the Research Team?

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Are You a Good Fit for This Trial?

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 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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• M281

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.

How Is the Trial Designed?

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+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

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 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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11339140/

Pharmacokinetics and Pharmacodynamics of Nipocalimab ... Efficacy and safety of M281 in adults with warm autoimmune hemolytic anemia. Available from: https://www.clinicaltrials.gov/ct2/show ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04119050

Study Details | NCT04119050 | Efficacy and Safety of M281 ... The main purpose of this study is to evaluate the efficacy and safety of M281 in participants with warm autoimmune hemolytic anemia (wAIHA). Detailed ...

3. jnj.com jnj.com/media-center/press-releases/new-nipocalimab-data-published-in-mabs-journal-details-differentiated-molecular-design-clinical-profile-and-potential-of-nipocalimab-to-treat-igg-driven-alloantibody-and-autoantibody-diseases

New nipocalimab data published in mAbs journal details ... Nipocalimab is a fully human IgG-1 monoclonal antibody that binds to FcRn, resulting in the reduction of circulating IgG levels including pathogenic IgG ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39197469/

Design of a Phase 3, Global, Multicenter, Randomized ... The phase 3 AZALEA study aims to evaluate the efficacy and safety of nipocalimab in a larger population at risk for severe HDFN.

5. prnewswire.com prnewswire.com/news-releases/new-nipocalimab-data-published-in-mabs-journal-details-differentiated-molecular-design-clinical-profile-and-potential-of-nipocalimab-to-treat-igg-driven-alloantibody-and-autoantibody-diseases-302375854.html

New nipocalimab data published in mAbs journal details ... Nipocalimab is a fully human IgG-1 monoclonal antibody that binds to FcRn, resulting in the reduction of circulating IgG levels including pathogenic IgG ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12255621/

Pharmacokinetics, Pharmacodynamics, and Safety of ... This study assessed the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of a single dose of nipocalimab in healthy Chinese volunteers.

7. jnjmedicalconnect.com jnjmedicalconnect.com/products/imaavy/medical-content/imaavy-overview-of-the-phase-23-energy-clinical-trial

IMAAVY - Overview of the Phase 2/3 ENERGY Clinical Trial Study design of ENERGY, a phase 2/3 clinical trial to assess the efficacy and safety of nipocalimab in warm autoimmune hemolytic anemia (wAIHA).