Nipocalimab for Hemolytic Disease of the Fetus and Newborn

(AZALEA Trial)

Recruiting at 61 trial locations

Overseen By Study Contact

Age: 18 - 65

Sex: Female

Trial Phase: Phase 3

Sponsor: Janssen Research & Development, LLC

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Multiple gestation, Hypertension, Immunodeficiency, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 35 weeks

120 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to assess the effectiveness of nipocalimab when compared to placebo in decreasing the risk of fetal anemia (a condition in which a baby's red blood cell volume falls below normal levels while the baby is developing in the womb) with live neonates in pregnant participants at risk for severe hemolytic disease of the fetus and newborn.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently taking systemic corticosteroids or other immunosuppressants for conditions unrelated to the pregnancy.

What data supports the effectiveness of the drug Nipocalimab for treating hemolytic disease of the fetus and newborn?

Research suggests that blocking the neonatal Fc receptor (FcRn) can prevent the transfer of harmful antibodies from mother to fetus, which is a key factor in immune-related diseases during pregnancy. Nipocalimab, an anti-FcRn antibody, has shown promise in blocking this receptor, potentially reducing the risk of these conditions. ^{1 2 3 4 5}

Is Nipocalimab safe for humans?

Nipocalimab, also known as M281, has been tested in a phase 1 study with healthy volunteers, showing it can block the neonatal Fc receptor effectively. This suggests it has been evaluated for safety in humans, although specific safety outcomes from the study are not detailed in the available information. ^{1 2 3 4 6}

How is the drug Nipocalimab unique in treating hemolytic disease of the fetus and newborn?

Nipocalimab is unique because it blocks the neonatal Fc receptor, preventing the transfer of harmful antibodies from the mother to the fetus, which is a novel approach compared to traditional treatments that do not target this specific mechanism. ^{1 2 4 7 8}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

This trial is for pregnant women between weeks 13 and 16^6/7 of gestation, who have had severe HDFN in a past pregnancy or have certain high-risk antibodies. They must be generally healthy with specific normal lab values and no multiple pregnancies, immunodeficiencies, malignancies within the last three years (except some skin cancers), uncontrolled hypertension, or recent use of certain immune therapies.

Inclusion Criteria

I am pregnant and between 13 to 16 weeks along.

Meeting study protocol-specified parameters for screening laboratory values

History of severe Hemolytic Disease of the Fetus and Newborn (HDFN) in a prior pregnancy with specific criteria

Exclusion Criteria

I do not have a severe or opportunistic infection.

I have had a heart attack, unstable heart disease, or stroke.

I am on immunosuppressive drugs for an inflammatory or autoimmune disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nipocalimab or placebo intravenously once weekly from randomization through gestational age Week 35

Up to 35 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including monitoring for adverse events and neonatal outcomes

24 weeks postpartum

Neonatal Monitoring

Monitoring of liveborn neonates for HDFN-related morbidities and other health outcomes

Up to 104 weeks

Treatment Details

Interventions

• Nipocalimab

Trial Overview The study tests nipocalimab's ability to reduce fetal anemia risk due to HDFN compared to a placebo. Participants will receive either nipocalimab or placebo while researchers monitor the health outcomes of their babies at birth.

Participant Groups

Group I: Nipocalimab Experimental Treatment 1 Intervention

Participants will receive nipocalimab intravenously (IV) once weekly (qw) from randomization through gestational age (GA) Week 35.

Group II: Placebo Placebo Group 1 Intervention

Participants will receive matching placebo IV qw from randomization through GA Week 35.

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 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 transferring maternal IgG antibodies to the fetus, which can lead to immune-mediated diseases if pathogenic antibodies are involved.

Blocking FcRn may offer a promising treatment approach for perinatal immune-mediated diseases by reducing the transfer of harmful antibodies to the fetus and lowering their levels in the mother's circulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting neonatal Fc receptor: potential clinical applications in pregnancy. Moise, KJ., Oepkes, D., Lopriore, E., et al.[2022]

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 study developed a mouse model to show that the neonatal Fc receptor (FcRn) is crucial for the development of fetal and neonatal immune thrombocytopenia (FNIT), as it facilitates the transport of maternal antibodies that destroy fetal platelets.

Treatment with anti-FcRn antibodies and intravenous IgG was effective in preventing FNIT, indicating that targeting FcRn could be a promising therapeutic approach for FNIT and similar diseases caused by maternal antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Animal model of fetal and neonatal immune thrombocytopenia: role of neonatal Fc receptor in the pathogenesis and therapy. Chen, P., Li, C., Lang, S., et al.[2021]

Blocking the neonatal Fc receptor (FcRn) with the anti-FcRn monoclonal antibody (mAb) 4470 during pregnancy significantly reduced the transfer of harmful maternal antibodies to the fetus, which is crucial for preventing neonatal diseases like arthrogryposis multiplex congenita (AMC).

Treatment with 4470 not only decreased the incidence of deformities in the offspring but also did not negatively impact maternal health or fetal development, suggesting it could be a safe and effective strategy for protecting against maternal autoantibody-related diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of Maternal-to-Fetal Transfer of IgG Antibodies by FcRn Blockade in a Mouse Model of Arthrogryposis Multiplex Congenita. Coutinho, E., Jacobson, L., Shock, A., et al.[2022]

The neonatal Fc receptor (FcRn) is functionally expressed in human immune cells, including monocytes, macrophages, and dendritic cells, indicating a potential role in IgG transport and protection from degradation.

FcRn binds human IgG at acidic pH, suggesting it may have unique IgG binding functions in immune cells compared to traditional Fc gamma receptors, which could influence immune responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MHC class I-related neonatal Fc receptor for IgG is functionally expressed in monocytes, intestinal macrophages, and dendritic cells. Zhu, X., Meng, G., Dickinson, BL., et al.[2022]

The neonatal Fc receptor (FcRn) plays a crucial role in enhancing the serum persistence and transcellular permeability of immunoglobulin G (IgG) and albumin, which is important for maintaining immunity throughout life.

FcRn's ability to facilitate the transport of IgG across mucosal barriers and its role in immune surveillance make it a valuable target for improving the absorption and effectiveness of IgG-based therapeutics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neonatal Fc receptor and its role in the absorption, distribution, metabolism and excretion of immunoglobulin G-based biotherapeutics. Giragossian, C., Clark, T., Piché-Nicholas, N., et al.[2019]

References

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

Modified antibody in fetal alloimmunization. [2021]

2. Poland pubmed.ncbi.nlm.nih.gov

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

3. England pubmed.ncbi.nlm.nih.gov

Targeting neonatal Fc receptor: potential clinical applications in pregnancy. [2022]

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

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

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

Animal model of fetal and neonatal immune thrombocytopenia: role of neonatal Fc receptor in the pathogenesis and therapy. [2021]

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

Inhibition of Maternal-to-Fetal Transfer of IgG Antibodies by FcRn Blockade in a Mouse Model of Arthrogryposis Multiplex Congenita. [2022]

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

MHC class I-related neonatal Fc receptor for IgG is functionally expressed in monocytes, intestinal macrophages, and dendritic cells. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Neonatal Fc receptor and its role in the absorption, distribution, metabolism and excretion of immunoglobulin G-based biotherapeutics. [2019]