M281 for Hemolytic Disease of the Fetus and Newborn

Recruiting at 19 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

14 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug M281 (Nipocalimab) for Hemolytic Disease of the Fetus and Newborn?

Research on similar treatments shows that antibodies targeting Fc gamma receptors can block immune responses that lead to conditions like hemolytic anemia, suggesting that M281 might work similarly by preventing harmful immune interactions in Hemolytic Disease of the Fetus and Newborn. ^{1 2 3 4 5}

Is M281 (Nipocalimab) safe for humans?

M281, also known as Nipocalimab, has been tested in a phase 1 study with healthy volunteers, showing it can block a specific receptor involved in immune responses. This suggests it has been evaluated for safety in humans, although specific safety outcomes from the study are not detailed in the available information. ^{3 4 6 7 8}

How does the drug M281 work differently from other treatments for Hemolytic Disease of the Fetus and Newborn?

M281 is unique because it blocks the neonatal Fc receptor, which is responsible for transferring harmful antibodies from the mother to the fetus. This mechanism helps prevent or reduce immune-related complications during pregnancy, offering a novel approach compared to existing treatments. ^{2 4 6 9 10}

What is the purpose of this trial?

This trial is testing a new drug called M281 to see if it is safe for pregnant women and their babies. It focuses on women at high risk for a serious blood condition in their babies. The goal is to prevent the need for blood transfusions before birth and ensure healthy births.

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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

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]

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]

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 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]

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]

References

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

HPA-1a-mediated platelet interaction with monocytes in vitro: involvement of Fcgamma receptor (FcgammaR) classes and inhibition by humanised monoclonal anti-FcgammaRI H22. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

Inhibition of monocyte and polymorphonuclear granulocyte immune phagocytosis by monoclonal antibodies specific for Fc gamma RI, II and III. [2019]

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

Modified antibody in fetal alloimmunization. [2021]

4. 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]

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

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

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

M281, an anti-FcRn antibody, inhibits IgG transfer in a human ex vivo placental perfusion model. [2019]

7. Poland pubmed.ncbi.nlm.nih.gov

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

8. England pubmed.ncbi.nlm.nih.gov

Human IgG lacking effector functions demonstrate lower FcRn-binding and reduced transplacental transport. [2018]

9. Germany pubmed.ncbi.nlm.nih.gov

FcRn: from molecular interactions to regulation of IgG pharmacokinetics and functions. [2018]

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

FcRn receptor-mediated pharmacokinetics of therapeutic IgG in the eye. [2022]