Hemolytic Disease of the Fetus and NewbornPhase 3AZALEANCT05912517
A Study of Nipocalimab in Pregnancies at Risk for Severe Hemolytic Disease of the Fetus and Newborn (HDFN)
A Phase 3 study testing Nipocalimab in people with Hemolytic Disease of the Fetus and Newborn, run by Janssen Research & Development, LLC at 69 sites in 18 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Hemolytic Disease of the Fetus and Newborn
- What is being tested?
- Nipocalimab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 69 sitesin 18 countries
- Study dates
- 20 Dec 2023to 8 Oct 2029
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Pregnant and an estimated gestational age (GA) (based on ultrasound dating) from Week 13^0/7 to Week 18^6/7 at randomization
- History of severe Hemolytic Disease of the Fetus and Newborn (HDFN) in a prior pregnancy defined as documented:
- fetal anemia as result of HDFN or fetal hydrops as result of HDFN or received greater than or equal to (>=)1 IUT as a result of HDFN or
- fetal loss or neonatal death as a result of HDFN, with maternal alloantibody titers for Rhesus antigen D protein (RhD), Kell, Kell Rhesus antigen C protein (Rhc), Rhesus antigen E protein (RhE), or RhC antigen above the critical levels (anti-Kell >=4; other >=16) and evidence of an antigen-positive fetus
- During the current pregnancy, presence of maternal alloantibody to RhD, Rhc, RhE, or RhC antigen with titers above the critical level (anti-Kell >= 4; other >=16) based on the designated central lab results at screening
- Evidence of antigen-positivity corresponding to the current maternal alloantibody (RhD, Kell, Rhc, RhE, or RhC) confirmed by non-invasive antigen cell-free fetal DNA (cffDNA) performed at the central laboratory
- Have screening lab test results within values within the study protocol-specified parameters: a) albumin >= lower limit of normal (LLN); b) alanine transaminase (AST) less than or equal to (<=) 2 × upper limit of normal (ULN); c) alanine transaminase (ALT) <=2 × ULN d) creatinine <=0.8 milligrams per deciliter (mg/dL), SI: <=70.7 micromole per liter (μmol/L), and Serum total immunoglobulins G (IgG) ≥ 600 mg/dL SI: >=6 g/L
- Medically stable on the basis of physical examination, medical history, vital signs, 12-lead ECG, and clinical lab tests performed at screening
Who cannot join
- Currently pregnant with a multiple gestation (twins or more)
- Evidence of fetal anemia prior to randomization in the current pregnancy
- History of severe preeclampsia prior to GA Week 34 or severe fetal growth restriction (estimated fetal weight <3rd percentile, based on local fetal growth normative standards) in a previous pregnancy
- Current uncontrolled hypertension
- History of myocardial infarction, unstable ischemic heart disease, or stroke
- Has any confirmed or suspected clinical immunodeficiency syndrome or has a family history of congenital or hereditary immunodeficiency unless confirmed absent in the participant
Show all 14Show fewer
- Has inflammatory or autoimmune diseases requiring immunosuppressive therapies that may jeopardize the safety of the participant
- Currently has a malignancy or has a history of malignancy within 3 years before screening (with the exception of localized basal cell carcinoma and/or squamous cell carcinoma skin cancer that has been adequately treated with no evidence of recurrence for at least 3 months before the first study intervention administration or cervical carcinoma in situ that has been treated with no evidence of recurrence for at least 3 months before the first study intervention)
- Is currently receiving systemic corticosteroids or other immunosuppressants for disorders unrelated to the pregnancy
- Has received or planning to receive plasmapheresis, immunoadsorption therapy, intravenous immunoglobulin (IV Ig), or any immunoglobulin (Ig)G fragment crystallizable (Fc)-related protein therapeutics during the current pregnancy
- Has a severe infection including opportunistic infections
- Presence of abnormal (protocol-specified) hematologic lab values during screening
- History of an unprovoked pulmonary embolism or history of recurrent deep vein thrombosis (DVT)
- The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Trial locations and contacts
69 sites in 18 countries. Contact the study team or a site near you to ask about taking part.
69 sites in 18 countries
United States22 sites, 21 recruiting
- Recruiting
Lehigh Valley Hospital
Allentown, Pennsylvania, 18103-6218
- Recruiting
Childrens Hospital Colorado
Aurora, Colorado, 80045
- Recruiting
University of Texas Dell Medical School Department of Women's Health
Austin, Texas, 78723
- Recruiting
Johns Hopkins Hospital
Baltimore, Maryland, 21287
- Recruiting
Boston Childrens Hospital
Boston, Massachusetts, 02115
- Recruiting
University of North Carolina (UNC) - School of Medicine
Chapel Hill, North Carolina, 27599-7516
- Recruiting
University of Cincinnati
Cincinnati, Ohio, 45267
- Recruiting
University Of Texas Medical Branch At Galveston
Galveston, Texas, 77555
- Suspended
Riley Children s Hospital
Indianapolis, Indiana, 46202
- Recruiting
University of Iowa
Iowa City, Iowa, 52242
- Recruiting
University of California at San Diego
La Jolla, California, 92037
- Recruiting
University of Kentucky Medical Center
Lexington, Kentucky, 40536
- Recruiting
Kaiser Permanente Los Angeles Medical Center
Los Angeles, California, 90027
- Recruiting
University of Miami
Miami, Florida, 33136
- Recruiting
Midwest Fetal Care Center
Minneapolis, Minnesota, 55404
- Recruiting
Intermountain Medical Center
Murray, Utah, 84107
- Recruiting
Columbia University Medical Center
New York, New York, 10032
- Recruiting
Macon & Joan Brock Virginia Health Sciences at Old Dominion University
Norfolk, Virginia, 23507
- Recruiting
Advocate Children's Hospital
Park Ridge, Illinois, 60068
- Recruiting
Oregon Health and Science University
Portland, Oregon, 97239
- Recruiting
UC Davis School of Medicine
Sacramento, California, 95817
- Recruiting
Seattle Children's Hospital
Seattle, Washington, 98105
United Kingdom6 sites, 6 recruiting
- Recruiting
Birmingham Women's Hospital
Birmingham, B15 2TG
- Recruiting
Leeds Teaching Hospitals NHS Trust
Leeds, LS9 7TF
- Recruiting
Kings College Hospital
London, SE5 9RS
- Recruiting
St Georges Hospital
London, SW17 0QT
- Recruiting
St.Mary's Hospital
Manchester, M13 9WL
- Recruiting
John Radcliffe Hospital
Oxford, OX3 9DU
Brazil5 sites, 5 recruiting
- Recruiting
Faculdade de Medicina Universidade Federal de Minas Gerais
Belo Horizonte, 30130 100
- Recruiting
Hospital das Clinicas - UFG
Goiânia, 74605 020
- Recruiting
Instituto de Medicina Integral Professor Fernando Figueira
Recife, 50070902
- Recruiting
IDOR - Regional Rio de Janeiro
Rio de Janeiro, 22281 100
- Recruiting
Hospital Das Clinicas Da Faculdade De Medicina Da USP
São Paulo, 05403-010
Japan5 sites, 3 recruiting
- Completed
Kyushu University Hospital
Fukuoka, 812 8582
- Recruiting
Gifu Prefectural General Medical Center
Gifu, 500-8717
- Recruiting
Osaka Womens and Childrens Hospital
Izumi-shi, 594-1101
- Recruiting
Toho University Medical Center Omori Hospital
Ōta-ku, 143-8541
- Completed
Miyagi Childrens Hospital
Sendai, 989-3126
Canada4 sites, 4 recruiting
- Recruiting
Centre Hospitalier Sainte Justine
Montreal, Quebec, H3T 1C5
- Recruiting
McGill University Health Centre
Montreal, Quebec, H4A 3J1
- Recruiting
Mount Sinai Hospital
Toronto, Ontario, M5G 1X5
- Recruiting
BC Women's Hospital University of British Columbia
Vancouver, British Columbia, V6H 3N1
France3 sites, 3 recruiting
- Recruiting
Hospices Civils de Lyon - Groupement Hospitalier Est - Hopital Femme Mere Enfant
Bron, 69500
- Recruiting
CHRU Lille
Lille, 59000
- Recruiting
Hopital Armand Trousseau
Paris, 75012
Germany3 sites, 3 recruiting
- Recruiting
Charite Universitaetsmedizin Berlin
Berlin, 10117
- Recruiting
Universitaetsklinikum Giessen und Marburg Standort Giessen
Giessen, 35392
- Recruiting
Universitaetsklinikum Hamburg Eppendorf
Hamburg, 20251
Israel3 sites, 3 recruiting
- Recruiting
Hadassah mount scopus
Jerusalem, 91240
- Recruiting
Rabin Medical Center
Petah Tikva, 49100
- Recruiting
The Chaim Sheba Medical Center
Ramat Gan, 5265601
Poland3 sites, 3 recruiting
- Recruiting
Instytut Centrum Zdrowia Matki Polki
Lodz, 93 338
- Recruiting
Instytut Matki i Dziecka
Warsaw, 01 211
- Recruiting
Panstwowy Instytut Medyczny MSWiA w Warszawie
Warsaw, 02 507
Spain3 sites, 3 recruiting
- Recruiting
Hosp Univ Vall D Hebron
Barcelona, 08035
- Recruiting
Hosp. Univ. La Paz
Madrid, 28046
- Recruiting
Hosp. Virgen Del Rocio
Seville, 41013
Argentina2 sites, 2 recruiting
- Recruiting
Hospital Italiano de Buenos Aires
Buenos Aires, C1199
- Recruiting
Hospital Privado Universitario De Cordoba
Córdoba, X5016KEH
Australia2 sites, 2 recruiting
- Recruiting
Mater Hospital Brisbane
South Brisbane, 4101
- Recruiting
Liverpool Hospital
Sydney, 2170
Austria2 sites, 2 recruiting
- Recruiting
Medizinische Universitaet Graz
Graz, 8036
- Recruiting
Medizinische Universitaet Wien
Vienna, 1090
Belgium2 sites, 2 recruiting
- Recruiting
C.H.U. Brugmann
Brussels, 1020
- Recruiting
Universitair Ziekenhuis Leuven
Leuven, 3000
Italy1 site, 1 recruiting
- Recruiting
Fondazione Policlinico Universitario A Gemelli IRCCS
Roma, 00168
Netherlands1 site, 1 recruiting
- Recruiting
Leiden University Medical Center
Leiden, 2333 ZA
Sweden1 site, 1 recruiting
- Recruiting
Karolinska Universitetssjukhuset Huddinge
Stockholm, 14186
About this study
Official title: A Phase 3 Randomized, Placebo-Controlled, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of Nipocalimab in Pregnancies at Risk for Severe Hemolytic Disease of the Fetus and Newborn (HDFN)
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.
- Being tested
- Nipocalimab, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NipocalimabDrug
Also called JNJ-80202135, M281, JNJ-86507083
Nipocalimab will be administered as an intravenous infusion.
PlaceboDrug
Placebo will be administered as an intravenous infusion.
| Study group | Role | What they receive |
|---|---|---|
| Nipocalimab | Experimental | Participants will receive nipocalimab intravenously (IV) once weekly (qw) from randomization through gestational age (GA) Week 35. Receives: Drug: Nipocalimab |
| Placebo | Placebo comparator | Participants will receive matching placebo IV qw from randomization through GA Week 35. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Pregnancies That did not Result in Fetal Loss, Intrauterine Transfusion (IUT), Hydrops Fetalis, or Neonatal Death
Percentage of pregnancies that did not result in fetal loss, IUT, hydrops fetalis, or neonatal death (during the neonatal period) will be reported. Hydrops fetalis is defined as the presence of greater than or equal to(>=)2 abnormal fluid collections in the fetus or neonate, such as ascites, pleural effusions, pericardial effusion, and generalized skin edema (skin thickness greater (>)5 millimeter [mm]). PMA is the time elapsed between the first day of the last menstrual period and birth (gestational age) plus the time elapsed after birth (chronological age).
Measured: From randomization in the study through 4 weeks of age or 41 weeks Postmenstrual Age (PMA) during neonatal period, whichever is later
Secondary outcomes (39)
Number of Participants With Hemolytic Disease of the Fetus and Newborn (HDFN) by Severity
Number of participants with HDFN by severity will be reported. The severity of HDFN is defined as: 5 (fatal): fetal or neonatal death due to any reason; 4 (severe): hydrops fetalis (in fetus or newborn) or receiving IUT during pregnancy as a result of HDFN but not 5 (fatal); 3 (moderate): neonatal exchange transfusions received as a result of HDFN related hemolysis and jaundice but not 4 (severe) or 5 (fatal); 2 (mild): neonatal simple transfusions received due to HDFN after birth, with or without phototherapy, but not 3 (moderate), 4 (severe), or 5 (fatal); and 1 (minimal or none): not in 2 (mild), 3 (moderate), 4 (severe), or 5 (fatal) as described above. Here database lock implies the last participant has given birth or terminated their pregnancy, completed the Week 4 visit after delivery, and whose neonate has also completed the Week 4 visit (or 41 weeks PMA, whichever is later) or died prior to this timepoint.
Measured: For first database lock: from randomization in the study through 4 weeks of age or 41 weeks PMA during neonatal period, whichever is later for the first database lock; for second database lock: through 12 weeks after birth
Time to First Occurrence of IUT or Hydrops Fetalis
Time to first occurrence of IUT or hydrops fetalis will be reported.
Measured: From randomization to delivery of baby (Up to 38 weeks)
Neonatal Mortality and Morbidity Index (NMMI) in Liveborn Neonates
The NMMI will be assessed with the following categories: fatal: fetal/neonatal death; major morbidity: any of intraventricular hemorrhage grade 3/4, seizures, hypoxic-ischemic encephalopathy, necrotizing enterocolitis stage 2/3, respiratory distress syndrome requiring mechanical ventilation, bronchopulmonary dysplasia requiring oxygen support, or persistent pulmonary hypertension; Minor morbidity: anemia requiring simple transfusion, hyperbilirubinemia requiring an exchange transfusion, hypotension requiring treatment, intraventricular hemorrhage grade 1/2, necrotizing enterocolitis stage 1, or respiratory distress syndrome not requiring mechanical ventilation; None: no major or minor morbidities described above. Hyperbilirubinemia requiring phototherapy will be classified in this category'
Measured: Through 38 weeks PMA or at discharge if earlier than 38 weeks PMA
Number of IUT's Received During the Pregnancy
Number of IUT's received during the pregnancy will be reported.
Measured: From randomization to delivery of baby (Up to 38 weeks)
Percentage of Pregnancies With Fetal Loss
Percentage of pregnancies with fetal loss will be reported.
Measured: Time to delivery of baby (Up to 38 weeks)
Percentage of Pregnancies With Fetal or Neonatal Death
Percentage of pregnancies with fetal or neonatal death (through the neonatal period) as a result of HDFN will be reported.
Measured: Through Week 4 or 41 weeks PMA
Percentage of Pregnancies With Hydrops Fetalis
Percentage of pregnancies with hydrops fetalis will be reported. Hydrops fetalis is defined as the presence of >=2 abnormal fluid collections in the fetus or neonate, such as ascites, pleural effusions, pericardial effusion, and generalized skin edema (skin thickness >5 mm).
Measured: Up to 41 weeks PMA
Percentage of Pregnancies Receiving IUT During Pregnancy
Percentage of pregnancies receiving IUT during pregnancy will be reported.
Measured: Up to 35 weeks of GA period
Gestational Age (GA) at First IUT
GA at first IUT will be reported.
Measured: Up to 35 weeks of GA period
Percentage of Pregnancies Receiving >1 IUT During Pregnancy
Percentage of pregnancies receiving >1 IUT during pregnancy will be reported.
Measured: Up to 35 weeks of GA period
Percentage of Pregnancies Receiving IUT or HDFN Resulting in Fetal Demise (Less Than) <GA Week 20
Percentage of pregnancies receiving IUT or HDFN resulting in fetal demise <GA Week 20 will be reported.
Measured: Up to 20 weeks
Gestational Age at Delivery
Gestational age at delivery will be reported.
Measured: Up to 38 weeks
Percentage of Pregnancies With Neonatal Death Through the Neonatal Period
Percentage of pregnancies with neonatal death through the neonatal period will be reported.
Measured: From randomization in the study through 4 weeks of age or 41 weeks PMA during neonatal period, whichever is later
Percentage of Liveborn Neonates With HDFN-related Morbidities Other Than Anemia and Hyperbilirubinemia or Jaundice
Percentage of liveborn neonates with HDFN-related morbidities other than anemia and hyperbilirubinemia or jaundice will be reported.
Measured: From day of birth up to 4 weeks
Absolute Weight of Liveborn Neonates or Infants
Absolute weight of liveborn neonates or infants will be reported.
Measured: Up to 104 weeks
Change From Baseline in Weight of Liveborn Neonates or Infants
Change from baseline in weight of liveborn neonates or infants will be reported.
Measured: Baseline to up to 104 weeks
Liveborn Neonates Length of Stay in Neonatal Intensive Care Unit
Liveborn neonates length of stay in neonatal intensive care unit will be reported.
Measured: From day of birth up to 27 days
Percentage of Liveborn Neonates Receiving Exchange Transfusions for HDFN
Percentage of liveborn neonates receiving exchange transfusions for HDFN will be reported.
Measured: From day of birth up to 27 days
Number of Neonatal Exchange Transfusions per Liveborn Neonate
Number of neonatal exchange transfusions per liveborn neonate will be reported.
Measured: From day of birth up to 27 days
Percentage of Liveborn Neonates or Infants with Simple Transfusions for HDFN
Percentage of liveborn neonates or infants with simple transfusions for HDFN through the neonatal period (for the first database lock) or 12 weeks (for the second database lock) after birth will be reported.
Measured: For first database lock: From birth up to 4 weeks; for second database lock: From birth up to 12 weeks
Number of Simple Transfusions for HDFN per Liveborn Neonate or Infant
Number of simple transfusions for HDFN per liveborn neonate or infant through the neonatal period (for the first database lock) or 12 weeks (for the second database lock) after birth will be reported.
Measured: For first database lock: From birth up to 4 weeks; for second database lock: From birth up to 12 weeks
Percentage of Liveborn Neonates With Hyperbilirubinemia Treated With Phototherapy
Percentage of liveborn neonates with hyperbilirubinemia treated with phototherapy will be reported.
Measured: From day of birth up to 27 days
Number of Days of Phototherapy Received for Hyperbilirubinemia per Liveborn Neonate
Number of days of phototherapy received for hyperbilirubinemia per liveborn neonate will be reported.
Measured: From day of birth up to 27 days
Percentage of Liveborn Neonates or Infants Receiving Intravenous Immunoglobulin (IVIg) for HDFN Treatment
Percentage of liveborn neonates or infants receiving IVIg for HDFN treatment will be reported.
Measured: For first database lock: From birth up to 4 weeks; for second database lock: From birth up to 12 weeks
Number of Maternal Deaths
Number of maternal deaths will be reported.
Measured: Form randomization up to 24 weeks postpartum
Number of Participants with Adverse Events (AEs)
Number of participants with AEs, serious adverse events, and AEs of special interest (AESIs), AE's leading to discontinuations, infections, serious infections, infusion reactions, and hypersensitivity reactions will be reported. Treatment-emergent adverse events associated with the following situations are considered as AESIs: hypoalbuminemia, clinically significant bleeding with a corresponding placental finding on ultrasound, maternal infections that led to clinically significant morbidities or mortalities in fetus or neonates, Infections that are severe or require intravenous (IV) anti-infective or operative or invasive intervention in maternal participants or neonates or infants, and infants with hypogammaglobulinemia.
Measured: From randomization up to 24 weeks postpartum
Number of Maternal Pregnancy Complications
Number of maternal pregnancy complications will be reported.
Measured: Up to 38 weeks
Number of IUT Related complications
Number of participants with IUT related complications will be reported.
Measured: Up to 35 weeks of GA period
Percentage of Pregnancies With Cesarean Delivery, Preterm Birth, Fetal Growth, and Preeclampsia
Percentage of pregnancies with cesarean delivery, cesarean delivery due to IUT complications, preterm birth <GA week 28, preterm birth <GA week 32, preterm birth <GA week 34, preterm birth <GA week 37, fetal growth restriction, and preeclampsia will be reported.
Measured: Up to 38 weeks of GA period
Percentage of Liveborn Neonates or Infants Who Died
Percentage of liveborn neonates or infants who died will be reported.
Measured: Up to 104 weeks
Percentage of Liveborn Neonates or Infants With AEs
Percentage of liveborn neonates or infants with AEs, SAEs, AESIs, infections, serious infections will be reported. An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. Any event requiring hospitalization (or prolongation of hospitalization) that occurs during participation in the study must be reported as an SAE.
Measured: Up to 104 weeks
Percentage of Liveborn Neonates or Infants Receiving IVIg for Non-HDFN Indications
Percentage of liveborn neonates or infants receiving IVIg for non-HDFN indications will be reported.
Measured: Up to 104 weeks
Percentage of Liveborn Neonates or Infants With Abnormal Hearing
Percentage of liveborn neonates or infants with abnormal hearing will be reported.
Measured: Up to 104 weeks
Bayley Scales of Infant Development and Toddler Development
The Bayley Scales of infant development is considered the standard assessment of early child development and includes cognition, language, motor skills, social emotional, and adaptive behavior will be reported. The Bayley Scales (3rd edition) are reference standards that measure infant and toddler development in five areas: cognition, language, motor skills, social-emotional and adaptive behavior. The cognition, language and motor skills scales are directly administered to the infant, while social-emotional, and adaptive behavior scales are caregiver questionnaires. The scores are standardized using norm reference samples with representative demographics and age adjusted for prematurity. Higher scores in the Bayley Scales indicate better outcomes.
Measured: Week 52 and 104
Change From Baseline in Generalized Anxiety Disorder 7-Item (GAD7) Over time During Pregnancy and Postpartum
Change from baseline in GAD7 over time during pregnancy and postpartum will be reported. The GAD-7 scale is a self-administered questionnaire designed to measure anxiety. The recall period for all items is the past 2 weeks. Responses to all items are rated on a 4-point Likert scale ranging from 0 "not at all" to 3 "nearly every day". The total score ranges from 0 to 21, with higher scores indicating higher severity of anxiety symptoms.
Measured: Baseline (Day 1) and Week 30 during pregnancy and Week 4 postpartum
Change From Baseline in Short Form 36 Version 2 (SF-36v2) Acute Form Domain Score
Change from baseline in SF-36v2 acute form domain score will be reported. The SF-36 version 2 acute is a self-administered, 36-item questionnaire measuring health-related quality of life and includes 8 domains that measure physical functioning, role limitations due to physical health problems, bodily pain, general health, vitality social functioning, role limitations due to emotional problems, and mental health. The 8 domains can be aggregated into 2 summary scales that reflect physical and mental health: a physical component summary and a mental component summary. Responses to all items are rated on a 3, 5, or 6-point Likert scale, with higher scores indicating better health status.
Measured: Baseline (Day 1) and Week 30 during pregnancy and Week 4 postpartum
Change From Baseline in EuroQol Five-dimension Questionnaire (EQ-5D-5L) Visual Analogue Scale (VAS) Score
Change from baseline in EQ-5D-5L visual analogue score will be reported. The EQ-5D descriptive system is comprised of 5 items across the following 5 dimensions: mobility, self-care, usual activities, pain or discomfort and anxiety or depression. The EQ-5D-5L uses a 5-point Likert response scale ranging from "no problems" to "extreme problems", with higher scores indicating better quality of life. EQ-5D-5L consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ-VAS). EQ-VAS score ranges from 0 to 100, where 0 = worst imaginable health state and 100 = best imaginable health state. Higher score indicates good health state.
Measured: Baseline (Day 1) and Week 30 during pregnancy and Week 4 postpartum
Change From Baseline in EuroQol 5-Dimension Descriptive (EQ-5D) Index Score
Change from baseline in EQ-5D index score will be reported. The EQ-5D descriptive system is comprised of 5 items across the following 5 dimensions: mobility, self-care, usual activities, pain or discomfort and anxiety or depression. The EQ-5D-5L descriptive system uses a 5-point Likert response scale ranging from "no problems" to "extreme problems", with higher scores indicating better quality of life.
Measured: Baseline (Day 1) and Week 30 during pregnancy and Week 4 postpartum
Infant Health-Related Quality of Life Instrument (IQI) Score for Neonate or Infant Overtime
IQI score for neonate or infant will be reported. The IQI consists of 7 health attributes including sleeping, feeding, breathing, stooling or poo, mood, skin, and interaction. Responses to all items are rated on a 4-point Likert scale, with higher scores indicating better quality of life.
Measured: Weeks 4, 8 and 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2023
- Study start20 Dec 2023
- Primary completion5 Aug 2027 (estimated)
- Study completion8 Oct 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hemolytic Disease of the Fetus and NewbornStudies of the same condition, open and under way.
- More trials run by Janssen Research & Development, LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The participants will be randomized in a 2:1 to receive nipocalimab and placebo treatment.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Janssen Research & Development, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Janssen Research & Development, LLC Clinical Trial, Study director, Janssen Research & Development, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05912517
- Sponsor's protocol ID
- CR109199
- Other IDs
- 80202135EBF3001, 2021-002359-12, 2022-502629-16-00
- Acronym
- AZALEA
- Status last verified
- Nov 2026
- First submitted
- 13 Jun 2023
- Last updated
- 3 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The data sharing policy of Johnson \& Johnson Innovative Medicine is available at www.innovativemedicine.jnj.com/our-innovation/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
Publications
Rego S, Ashimi Balogun O, Emanuel K, Overcash R, Gonzalez JM, Denomme GA, Hoskovec J, King H, Wilson A, Wynn J, Moise KJ Jr. Cell-Free DNA Analysis for the Determination of Fetal Red Blood Cell Antigen Genotype in Individuals With Alloimmunized Pregnancies. Obstet Gynecol. 2024 Oct 1;144(4):436-443. doi: 10.1097/AOG.0000000000005692. Epub 2024 Jul 25.
PubMed 39053010
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3 Randomized, Placebo-Controlled, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of Nipocalimab in Pregnancies at Risk for Severe Hemolytic Disease of the Fetus and Newborn (HDFN)
- ClinicalTrials.gov ID
- NCT05912517
- Acronym / sponsor ID
- AZALEA / CR109199
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Janssen Research & Development, LLCIndustry (pharma, biotech, devices)
- Study start
- 20 Dec 2023 (actual)
- Primary completion
- 5 Aug 2027 (estimated)
- Study completion
- 8 Oct 2029 (estimated)
- First posted
- 22 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- The participants will be randomized in a 2:1 to receive nipocalimab and placebo treatment.
| Arm | Type | Receives |
|---|---|---|
| Nipocalimab | Experimental | Drug: NipocalimabParticipants will receive nipocalimab intravenously (IV) once weekly (qw) from randomization through gestational age (GA) Week 35. |
| Placebo | Placebo comparator | Drug: PlaceboParticipants will receive matching placebo IV qw from randomization through GA Week 35. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Pregnant and an estimated gestational age (GA) (based on ultrasound dating) from Week 13^0/7 to Week 18^6/7 at randomization
- History of severe Hemolytic Disease of the Fetus and Newborn (HDFN) in a prior pregnancy defined as documented:
- During the current pregnancy, presence of maternal alloantibody to RhD, Rhc, RhE, or RhC antigen with titers above the critical level (anti-Kell >= 4; other >=16) based on the designated central lab results at screening
- Evidence of antigen-positivity corresponding to the current maternal alloantibody (RhD, Kell, Rhc, RhE, or RhC) confirmed by non-invasive antigen cell-free fetal DNA (cffDNA) performed at the central laboratory
- Have screening lab test results within values within the study protocol-specified parameters: a) albumin >= lower limit of normal (LLN); b) alanine transaminase (AST) less than or equal to (<=) 2 × upper limit of normal (ULN); c) alanine transaminase (ALT) <=2 × ULN d) creatinine <=0.8 milligrams per deciliter (mg/dL), SI: <=70.7 micromole per liter (μmol/L), and Serum total immunoglobulins G (IgG) ≥ 600 mg/dL SI: >=6 g/L
Key exclusion criteria (14 listed)
- Currently pregnant with a multiple gestation (twins or more)
- Evidence of fetal anemia prior to randomization in the current pregnancy
- History of severe preeclampsia prior to GA Week 34 or severe fetal growth restriction (estimated fetal weight <3rd percentile, based on local fetal growth normative standards) in a previous pregnancy
- Current uncontrolled hypertension
- History of myocardial infarction, unstable ischemic heart disease, or stroke
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NipocalimabAlso: JNJ-80202135, M281, JNJ-86507083Nipocalimab will be administered as an intravenous infusion. | Drug | Nipocalimab |
| PlaceboPlacebo will be administered as an intravenous infusion. | Drug | Placebo |
Primary outcome
Percentage of Pregnancies That did not Result in Fetal Loss, Intrauterine Transfusion (IUT), Hydrops Fetalis, or Neonatal Death
Time frame: From randomization in the study through 4 weeks of age or 41 weeks Postmenstrual Age (PMA) during neonatal period, whichever is later
Percentage of pregnancies that did not result in fetal loss, IUT, hydrops fetalis, or neonatal death (during the neonatal period) will be reported. Hydrops fetalis is defined as the presence of greater than or equal to(>=)2 abnormal fluid collections in the fetus or neonate, such as ascites, pleural effusions, pericardial effusion, and generalized skin edema (skin thickness greater (>)5 millimeter [mm]). PMA is the time elapsed between the first day of the last menstrual period and birth (gestational age) plus the time elapsed after birth (chronological age).
39 secondary outcomes
Number of Participants With Hemolytic Disease of the Fetus and Newborn (HDFN) by Severity
Time frame: For first database lock: from randomization in the study through 4 weeks of age or 41 weeks PMA during neonatal period, whichever is later for the first database lock; for second database lock: through 12 weeks after birth
Time to First Occurrence of IUT or Hydrops Fetalis
Time frame: From randomization to delivery of baby (Up to 38 weeks)
Neonatal Mortality and Morbidity Index (NMMI) in Liveborn Neonates
Time frame: Through 38 weeks PMA or at discharge if earlier than 38 weeks PMA
Number of IUT's Received During the Pregnancy
Time frame: From randomization to delivery of baby (Up to 38 weeks)
Percentage of Pregnancies With Fetal Loss
Time frame: Time to delivery of baby (Up to 38 weeks)
Percentage of Pregnancies With Fetal or Neonatal Death
Time frame: Through Week 4 or 41 weeks PMA
Percentage of Pregnancies With Hydrops Fetalis
Time frame: Up to 41 weeks PMA
Percentage of Pregnancies Receiving IUT During Pregnancy
Time frame: Up to 35 weeks of GA period
Gestational Age (GA) at First IUT
Time frame: Up to 35 weeks of GA period
Percentage of Pregnancies Receiving >1 IUT During Pregnancy
Time frame: Up to 35 weeks of GA period
Percentage of Pregnancies Receiving IUT or HDFN Resulting in Fetal Demise (Less Than) <GA Week 20
Time frame: Up to 20 weeks
Gestational Age at Delivery
Time frame: Up to 38 weeks
Percentage of Pregnancies With Neonatal Death Through the Neonatal Period
Time frame: From randomization in the study through 4 weeks of age or 41 weeks PMA during neonatal period, whichever is later
Percentage of Liveborn Neonates With HDFN-related Morbidities Other Than Anemia and Hyperbilirubinemia or Jaundice
Time frame: From day of birth up to 4 weeks
Absolute Weight of Liveborn Neonates or Infants
Time frame: Up to 104 weeks
Change From Baseline in Weight of Liveborn Neonates or Infants
Time frame: Baseline to up to 104 weeks
Liveborn Neonates Length of Stay in Neonatal Intensive Care Unit
Time frame: From day of birth up to 27 days
Percentage of Liveborn Neonates Receiving Exchange Transfusions for HDFN
Time frame: From day of birth up to 27 days
Number of Neonatal Exchange Transfusions per Liveborn Neonate
Time frame: From day of birth up to 27 days
Percentage of Liveborn Neonates or Infants with Simple Transfusions for HDFN
Time frame: For first database lock: From birth up to 4 weeks; for second database lock: From birth up to 12 weeks
Number of Simple Transfusions for HDFN per Liveborn Neonate or Infant
Time frame: For first database lock: From birth up to 4 weeks; for second database lock: From birth up to 12 weeks
Percentage of Liveborn Neonates With Hyperbilirubinemia Treated With Phototherapy
Time frame: From day of birth up to 27 days
Number of Days of Phototherapy Received for Hyperbilirubinemia per Liveborn Neonate
Time frame: From day of birth up to 27 days
Percentage of Liveborn Neonates or Infants Receiving Intravenous Immunoglobulin (IVIg) for HDFN Treatment
Time frame: For first database lock: From birth up to 4 weeks; for second database lock: From birth up to 12 weeks
Number of Maternal Deaths
Time frame: Form randomization up to 24 weeks postpartum
Number of Participants with Adverse Events (AEs)
Time frame: From randomization up to 24 weeks postpartum
Number of Maternal Pregnancy Complications
Time frame: Up to 38 weeks
Number of IUT Related complications
Time frame: Up to 35 weeks of GA period
Percentage of Pregnancies With Cesarean Delivery, Preterm Birth, Fetal Growth, and Preeclampsia
Time frame: Up to 38 weeks of GA period
Percentage of Liveborn Neonates or Infants Who Died
Time frame: Up to 104 weeks
Percentage of Liveborn Neonates or Infants With AEs
Time frame: Up to 104 weeks
Percentage of Liveborn Neonates or Infants Receiving IVIg for Non-HDFN Indications
Time frame: Up to 104 weeks
Percentage of Liveborn Neonates or Infants With Abnormal Hearing
Time frame: Up to 104 weeks
Bayley Scales of Infant Development and Toddler Development
Time frame: Week 52 and 104
Change From Baseline in Generalized Anxiety Disorder 7-Item (GAD7) Over time During Pregnancy and Postpartum
Time frame: Baseline (Day 1) and Week 30 during pregnancy and Week 4 postpartum
Change From Baseline in Short Form 36 Version 2 (SF-36v2) Acute Form Domain Score
Time frame: Baseline (Day 1) and Week 30 during pregnancy and Week 4 postpartum
Change From Baseline in EuroQol Five-dimension Questionnaire (EQ-5D-5L) Visual Analogue Scale (VAS) Score
Time frame: Baseline (Day 1) and Week 30 during pregnancy and Week 4 postpartum
Change From Baseline in EuroQol 5-Dimension Descriptive (EQ-5D) Index Score
Time frame: Baseline (Day 1) and Week 30 during pregnancy and Week 4 postpartum
Infant Health-Related Quality of Life Instrument (IQI) Score for Neonate or Infant Overtime
Time frame: Weeks 4, 8 and 52
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2026.
- Derived from this study: PubMed 39053010Rego S, Ashimi Balogun O, Emanuel K, Overcash R, Gonzalez JM, Denomme GA, Hoskovec J, King H, Wilson A, Wynn J, Moise KJ Jr. Cell-Free DNA Analysis for the Determination of Fetal Red Blood Cell Antigen Genotype in Individuals With Alloimmunized Pregnancies. Obstet Gynecol. 2024 Oct 1;144(4):436-443. doi: 10.1097/AOG.0000000000005692. Epub 2024 Jul 25.
- Azalea Study Website (for the United States only)Link provided by the sponsor.
- Participant Recruitment PosterLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. The data sharing policy of Johnson \& Johnson Innovative Medicine is available at www.innovativemedicine.jnj.com/our-innovation/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Janssen Research & Development, LLC Clinical Trial study director
Janssen Research & Development, LLC
69 sites in 18 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Nipocalimab in people with Hemolytic Disease of the Fetus and Newborn, run by Janssen Research & Development, LLC at 69 sites in 18 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 3 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 69 sites in United States, United Kingdom, Brazil, Japan, Canada and 13 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Study Contact (844-434-4210, Participate-In-This-Study1@its.jnj.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Pregnancies That did not Result in Fetal Loss, Intrauterine Transfusion (IUT), Hydrops Fetalis, or Neonatal Death (time frame: From randomization in the study through 4 weeks of age or 41 weeks Postmenstrual Age (PMA) during neonatal period, whichever is later). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05912517, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2026.