M281 for Hemolytic Disease of the Fetus and Newborn

No longer recruiting at 20 trial locations

Overseen By Study Contact

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Janssen Research & Development, LLC

Must not be taking: Corticosteroids, Immunosuppressants, Antibody-based drugs

Disqualifiers: Multiples pregnancy, Hypertension, Infections, 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

Duration: Up to 32 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new treatment called M281 (Nipocalimab, a human monoclonal antibody) for pregnant women at high risk of Early Onset Severe Hemolytic Disease of the Fetus and Newborn (EOS-HDFN). The trial aims to assess the safety of M281 for both mother and baby and to determine if it can prevent the need for transfusions before birth. Women who have experienced complications such as severe fetal anemia, fetal hydrops (fluid buildup in a baby's tissues), or stillbirths due to hemolytic disease in previous pregnancies may be suitable candidates for this trial. Participants must commit to receiving regular care and vaccinations during their pregnancy. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude those who require treatment with corticosteroids or immunosuppression for conditions unrelated to pregnancy. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that M281 is likely to be safe for humans?

Research has shown that M281, also known as nipocalimab, is being tested for safety in pregnant women at risk for severe Hemolytic Disease of the Fetus and Newborn (HDFN). Earlier studies found that nipocalimab, a monoclonal antibody, works by blocking a specific part of the immune system. In these early studies, most participants tolerated it well, with only mild side effects reported.

These side effects included headaches and mild reactions at the injection site. No serious safety issues emerged in these studies. Notably, while M281 is still under investigation, it has received a Breakthrough Therapy Designation from the FDA for this condition, indicating promising early results.

Since this trial is in a middle phase, some understanding of the treatment's safety exists, but more information is needed. Prospective participants can feel reassured by the existing safety record but should discuss any concerns with their doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for Hemolytic Disease of the Fetus and Newborn (HDFN) involve managing symptoms and preventing the mother's immune system from attacking the baby's red blood cells, often using interventions like IVIG or blood transfusions. But M281 works differently, targeting the neonatal Fc receptor (FcRn) to reduce the levels of harmful antibodies that cause the disease. This unique mechanism of action could potentially offer more effective management of HDFN by directly addressing the root cause rather than just alleviating symptoms. Researchers are excited about M281 because it promises a more targeted approach, which could lead to better outcomes for both mothers and babies.

What evidence suggests that M281 might be an effective treatment for Hemolytic Disease of the Fetus and Newborn?

Research has shown that M281, also known as nipocalimab, targets a specific receptor in the body. This action helps prevent harmful antibodies from attacking the unborn baby, which is crucial in conditions like Hemolytic Disease of the Fetus and Newborn (HDFN). Previous studies found that nipocalimab is a potent antibody that binds effectively to its target. Early results suggest this treatment might reduce the need for blood transfusions before birth and support healthier deliveries. Although more research is needed, initial findings are promising for mothers at high risk of severe HDFN. Participants in this trial will receive M281 to further evaluate its effectiveness and safety in this condition. ^{1 2 3 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?

This trial is for pregnant women at least 18 years old, between 8-14 weeks gestation, who have a high risk of severe HDFN due to previous pregnancy complications or specific maternal alloantibody titers. Participants must be willing to receive standard care including intrauterine transfusions if needed and agree to recommended vaccinations.

Inclusion Criteria

My blood test shows I am carrying a baby with a specific genetic marker.

Maternal alloantibody titers for anti-D of >=32, or anti-Kell titers >=4

I had a stillbirth due to complications related to HDFN.

Exclusion Criteria

I need corticosteroids or immunosuppressants for a condition not related to pregnancy.

I have had severe bladder infections or more than 4 UTIs in the last year.

I haven't had any live vaccines recently and don't plan to while on nipocalimab.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive M281 throughout their pregnancy to prevent Early Onset Severe Hemolytic Disease of the Fetus and Newborn

Up to 32 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of fetal hydrops

24 weeks post birth

What Are the Treatments Tested in This Trial?

Interventions

• M281

Trial Overview The study tests the safety and effectiveness of M281 in preventing Early Onset Severe Hemolytic Disease of the Fetus and Newborn (EOS-HDFN). Success is measured by live births after week 32 without needing an intrauterine transfusion during pregnancy.

How Is the Trial Designed?

Group I: M281 Experimental Treatment 1 Intervention

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

The neonatal Fc receptor (FcRn) is crucial for the elimination of intravitreally administered full-length immunoglobulin G (IgG) across the blood-retinal barrier, as shown in studies comparing wild-type and FcRn knockout mice.

In laser-photocoagulated retinas, the upregulation of FcRn leads to a faster elimination of IgG into the bloodstream compared to normal retinas, highlighting the receptor's role in retinal response to injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FcRn receptor-mediated pharmacokinetics of therapeutic IgG in the eye. Kim, H., Robinson, SB., Csaky, KG.[2022]

Researchers are developing a therapeutic antibody aimed at preventing fetal and neonatal alloimmune thrombocytopenia (FNAIT) by blocking harmful antibodies from sensitized mothers, which could protect affected fetuses.

The engineered antibody is designed to avoid activating conventional Fc receptors while still interacting with FcRn, enabling it to cross the placenta and provide protection to the fetus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modified antibody in fetal alloimmunization. Bussel, JB., McFarland, JG.[2021]

M281, a monoclonal antibody that blocks the neonatal Fc receptor, rapidly saturates this receptor in placental cells, which could help prevent harmful immunoglobulin G transfer from mother to fetus.

In experiments, M281 significantly reduced the transfer of the immunoglobulin G antibody adalimumab across the placenta, indicating its potential as a therapeutic agent to protect against fetal and neonatal diseases linked to maternal antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

M281, an anti-FcRn antibody, inhibits IgG transfer in a human ex vivo placental perfusion model. Roy, S., Nanovskaya, T., Patrikeeva, S., 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]

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 neonatal Fc receptor (FcRn) plays a crucial role in transferring maternal IgG antibodies to the fetus, which is essential for providing immune protection during early life.

Beyond its role in antibody transfer, FcRn is also important for maintaining stable levels of IgG in the bloodstream, highlighting its significance in immune system regulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The neonatal receptor Fc gamma(FcRn)--structure and function]. Mikulska, JE.[2006]

Citations

1. 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.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03842189

NCT03842189 | A Study to Evaluate the Safety, Efficacy, ... The effectiveness of the investigational drug M281 will be measured by looking at the percentage of participants with live birth at or after gestational age (GA) ...

3. rarediseaseadvisor.com rarediseaseadvisor.com/reports/freesia-3-phase-3-trial-investigate-nipocalimab-pregnancies-risk-fnait/

Phase 3 Trial to Investigate Nipocalimab in Pregnancies at ... Nipocalimab is a fully human, immunoglobulin G1, high-affinity, neonatal Fc receptor-blocking monoclonal antibody designed to inhibit ...

4. jnjmedicalconnect.com jnjmedicalconnect.com/products/imaavy/medical-content/imaavy-clinical-studies-in-hemolytic-disease-of-the-fetus-and-newborn-hdfn

IMAAVY - Clinical Studies in Hemolytic Disease of ... A summary of the available clinical data from the IMAAVY™ (nipocalimab-aahu) clinical studies in Hemolytic Disease of the Fetus and Newborn ...

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

Pharmacokinetics and Pharmacodynamics of Nipocalimab ... Nipocalimab is a high-affinity, fully human, effectorless immunoglobulin G1 monoclonal antibody targeting the neonatal Fc receptor and is currently under ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03842189

NCT03842189 | A Study to Evaluate the Safety, Efficacy, ... The purpose of this study is to evaluate the safety in mother and neonate/infant of M281 administered to pregnant women who are at high risk for Early Onset ...

7. jnj.com jnj.com/media-center/press-releases/johnson-johnsons-nipocalimab-granted-u-s-fda-breakthrough-therapy-designation-for-the-treatment-of-individuals-at-high-risk-for-severe-hemolytic-disease-of-the-fetus-and-newborn-hdfn

Breakthrough Therapy Designation for nipocalimab ... Nipocalimab is currently the only therapy reported to be in clinical development for the treatment of alloimmunized pregnant individuals at risk of severe HDFN.