Nipocalimab for Hemolytic Disease of the Fetus and Newborn

(AZALEA Trial)

Recruiting at 73 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether nipocalimab (an anti-FcRn monoclonal antibody) can prevent fetal anemia (low red blood cell count in a developing baby) in pregnant women at high risk for severe hemolytic disease of the fetus and newborn. Participants will receive either nipocalimab or a placebo to evaluate the treatment's effectiveness. Pregnant women who have experienced fetal anemia or related conditions in past pregnancies and have specific antibodies in their blood during this pregnancy may qualify for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

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

Research has shown that nipocalimab is generally well-tolerated. Administered through an IV (intravenous) treatment, it has been tested in pregnant women and their babies. These studies focused on safety and found promising results, with no major safety concerns reported.

In earlier studies, participants did not experience significant side effects, indicating that serious issues were uncommon. Nipocalimab has received "Breakthrough Therapy Designation" from the FDA, highlighting its potential for conditions like severe hemolytic disease of the fetus and newborn, where new options are needed.

While confidence in its safety exists, ongoing clinical trials aim to gather more data and confirm these findings. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Nipocalimab is unique because it offers a new approach to treating Hemolytic Disease of the Fetus and Newborn (HDFN). Unlike traditional treatments that primarily focus on managing symptoms, nipocalimab targets the underlying cause by blocking the activity of antibodies responsible for the disease. This mechanism of action is different from current options like intrauterine transfusions, which temporarily alleviate symptoms. Researchers are excited about nipocalimab because it has the potential to provide a more effective and lasting solution by addressing the root of the problem, potentially reducing the need for invasive procedures.

What evidence suggests that nipocalimab might be an effective treatment for fetal anemia?

Research has shown that nipocalimab, which participants in this trial may receive, may help delay or prevent anemia in unborn babies. Studies have found that nipocalimab can reduce the need for blood transfusions given to the baby before birth. In earlier trials, 54% of participants who received nipocalimab had a live birth, which is encouraging for those at risk of severe hemolytic disease of the fetus and newborn, a condition where the baby's red blood cells break down too quickly. These findings suggest that nipocalimab could effectively reduce risks associated with this condition. ^{1 2 5 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 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.

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

Meeting study protocol-specified parameters for screening laboratory values

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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 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]

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]

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) 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]

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 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]

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]

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. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/89/NCT03842189/SAP_001.pdf

NCT03842189 This is a multicenter, open-label phase 2 study to assess the safety, efficacy, pharmacokinetics, and pharmacodynamics of nipocalimab administered to pregnant ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39115062/

Nipocalimab in Early-Onset Severe Hemolytic Disease of ... Conclusions: Nipocalimab treatment delayed or prevented fetal anemia or intrauterine transfusions, as compared with the historical benchmark, in ...

4. 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 ...

5. jnj.com jnj.com/media-center/press-releases/groundbreaking-nipocalimab-study-of-pregnant-individuals-at-high-risk-for-early-onset-severe-hemolytic-disease-of-the-fetus-and-newborn-published-in-the-new-england-journal-of-medicine

Groundbreaking nipocalimab study of pregnant individuals ... Nipocalimab delayed or prevented severe fetal anemia and 54 percent of study participants in the Phase 2 UNITY study achieved a live birth ...

6. 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.

7. pharmacytimes.com pharmacytimes.com/view/novel-drug-may-decrease-risk-of-severe-anemia-in-the-fetus-newborn

Novel Drug May Decrease Risk of Severe Anemia in the ... JNJ-80202135 (nipocalimab) treats hemolytic disease of the fetus and newborn caused by maternal red blood cells.