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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05912517




Registration number
NCT05912517
Ethics application status
Date submitted
13/06/2023
Date registered
22/06/2023

Titles & IDs
Public title
A Study of Nipocalimab in Pregnancies at Risk for Severe Hemolytic Disease of the Fetus and Newborn (HDFN)
Scientific 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)
Secondary ID [1] 0 0
2021-002359-12
Secondary ID [2] 0 0
CR109199
Universal Trial Number (UTN)
Trial acronym
AZALEA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hemolytic Disease of the Fetus and Newborn 0 0
Condition category
Condition code
Blood 0 0 0 0
Other blood disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Nipocalimab
Treatment: Drugs - Placebo

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

Placebo comparator: Placebo - Participants will receive matching placebo IV qw from randomization through GA Week 35.


Treatment: Drugs: Nipocalimab
Nipocalimab will be administered as an intravenous infusion.

Treatment: Drugs: Placebo
Placebo will be administered as an intravenous infusion.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Pregnancies That did not Result in Fetal Loss, Intrauterine Transfusion (IUT), Hydrops Fetalis, or Neonatal Death
Timepoint [1] 0 0
From randomization in the study through 4 weeks of age or 41 weeks Postmenstrual Age (PMA) during neonatal period, whichever is later
Secondary outcome [1] 0 0
Number of Participants With Hemolytic Disease of the Fetus and Newborn (HDFN) by Severity
Timepoint [1] 0 0
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
Secondary outcome [2] 0 0
Time to First Occurrence of IUT or Hydrops Fetalis
Timepoint [2] 0 0
From randomization to delivery of baby (Up to 38 weeks)
Secondary outcome [3] 0 0
Neonatal Mortality and Morbidity Index (NMMI) in Liveborn Neonates
Timepoint [3] 0 0
Through 38 weeks PMA or at discharge if earlier than 38 weeks PMA
Secondary outcome [4] 0 0
Number of IUT's Received During the Pregnancy
Timepoint [4] 0 0
From randomization to delivery of baby (Up to 38 weeks)
Secondary outcome [5] 0 0
Percentage of Pregnancies With Fetal Loss
Timepoint [5] 0 0
Time to delivery of baby (Up to 38 weeks)
Secondary outcome [6] 0 0
Percentage of Pregnancies With Fetal or Neonatal Death
Timepoint [6] 0 0
Through Week 4 or 41 weeks PMA
Secondary outcome [7] 0 0
Percentage of Pregnancies With Hydrops Fetalis
Timepoint [7] 0 0
Up to 41 weeks PMA
Secondary outcome [8] 0 0
Percentage of Pregnancies Receiving IUT During Pregnancy
Timepoint [8] 0 0
Up to 35 weeks of GA period
Secondary outcome [9] 0 0
Gestational Age (GA) at First IUT
Timepoint [9] 0 0
Up to 35 weeks of GA period
Secondary outcome [10] 0 0
Percentage of Pregnancies Receiving >1 IUT During Pregnancy
Timepoint [10] 0 0
Up to 35 weeks of GA period
Secondary outcome [11] 0 0
Percentage of Pregnancies Receiving IUT or HDFN Resulting in Fetal Demise (Less Than) <GA Week 20
Timepoint [11] 0 0
Up to 20 weeks
Secondary outcome [12] 0 0
Gestational Age at Delivery
Timepoint [12] 0 0
Up to 38 weeks
Secondary outcome [13] 0 0
Percentage of Pregnancies With Neonatal Death Through the Neonatal Period
Timepoint [13] 0 0
From randomization in the study through 4 weeks of age or 41 weeks PMA during neonatal period, whichever is later
Secondary outcome [14] 0 0
Percentage of Liveborn Neonates With HDFN-related Morbidities Other Than Anemia and Hyperbilirubinemia or Jaundice
Timepoint [14] 0 0
From day of birth up to 4 weeks
Secondary outcome [15] 0 0
Absolute Weight of Liveborn Neonates or Infants
Timepoint [15] 0 0
Up to 104 weeks
Secondary outcome [16] 0 0
Change From Baseline in Weight of Liveborn Neonates or Infants
Timepoint [16] 0 0
Baseline to up to 104 weeks
Secondary outcome [17] 0 0
Liveborn Neonates Length of Stay in Neonatal Intensive Care Unit
Timepoint [17] 0 0
From day of birth up to 27 days
Secondary outcome [18] 0 0
Percentage of Liveborn Neonates Receiving Exchange Transfusions for HDFN
Timepoint [18] 0 0
From day of birth up to 27 days
Secondary outcome [19] 0 0
Number of Neonatal Exchange Transfusions per Liveborn Neonate
Timepoint [19] 0 0
From day of birth up to 27 days
Secondary outcome [20] 0 0
Percentage of Liveborn Neonates or Infants with Simple Transfusions for HDFN
Timepoint [20] 0 0
For first database lock: From birth up to 4 weeks; for second database lock: From birth up to 12 weeks
Secondary outcome [21] 0 0
Number of Simple Transfusions for HDFN per Liveborn Neonate or Infant
Timepoint [21] 0 0
For first database lock: From birth up to 4 weeks; for second database lock: From birth up to 12 weeks
Secondary outcome [22] 0 0
Percentage of Liveborn Neonates With Hyperbilirubinemia Treated With Phototherapy
Timepoint [22] 0 0
From day of birth up to 27 days
Secondary outcome [23] 0 0
Number of Days of Phototherapy Received for Hyperbilirubinemia per Liveborn Neonate
Timepoint [23] 0 0
From day of birth up to 27 days
Secondary outcome [24] 0 0
Percentage of Liveborn Neonates or Infants Receiving Intravenous Immunoglobulin (IVIg) for HDFN Treatment
Timepoint [24] 0 0
For first database lock: From birth up to 4 weeks; for second database lock: From birth up to 12 weeks
Secondary outcome [25] 0 0
Number of Maternal Deaths
Timepoint [25] 0 0
Form randomization up to 24 weeks postpartum
Secondary outcome [26] 0 0
Number of Participants with Adverse Events (AEs)
Timepoint [26] 0 0
From randomization up to 24 weeks postpartum
Secondary outcome [27] 0 0
Number of Maternal Pregnancy Complications
Timepoint [27] 0 0
Up to 38 weeks
Secondary outcome [28] 0 0
Number of IUT Related complications
Timepoint [28] 0 0
Up to 35 weeks of GA period
Secondary outcome [29] 0 0
Percentage of Pregnancies With Cesarean Delivery, Preterm Birth, Fetal Growth, and Preeclampsia
Timepoint [29] 0 0
Up to 38 weeks of GA period
Secondary outcome [30] 0 0
Percentage of Liveborn Neonates or Infants Who Died
Timepoint [30] 0 0
Up to 104 weeks
Secondary outcome [31] 0 0
Percentage of Liveborn Neonates or Infants With AEs
Timepoint [31] 0 0
Up to 104 weeks
Secondary outcome [32] 0 0
Percentage of Liveborn Neonates or Infants Receiving IVIg for Non-HDFN Indications
Timepoint [32] 0 0
Up to 104 weeks
Secondary outcome [33] 0 0
Percentage of Liveborn Neonates or Infants With Abnormal Hearing
Timepoint [33] 0 0
Up to 104 weeks
Secondary outcome [34] 0 0
Bayley Scales of Infant Development and Toddler Development
Timepoint [34] 0 0
Week 52 and 104
Secondary outcome [35] 0 0
Change From Baseline in Generalized Anxiety Disorder 7-Item (GAD7) Over time During Pregnancy and Postpartum
Timepoint [35] 0 0
Baseline (Day 1) and Week 30 during pregnancy and Week 4 postpartum
Secondary outcome [36] 0 0
Change From Baseline in Short Form 36 Version 2 (SF-36v2) Acute Form Domain Score
Timepoint [36] 0 0
Baseline (Day 1) and Week 30 during pregnancy and Week 4 postpartum
Secondary outcome [37] 0 0
Change From Baseline in EuroQol Five-dimension Questionnaire (EQ-5D-5L) Visual Analogue Scale (VAS) Score
Timepoint [37] 0 0
Baseline (Day 1) and Week 30 during pregnancy and Week 4 postpartum
Secondary outcome [38] 0 0
Change From Baseline in EuroQol 5-Dimension Descriptive (EQ-5D) Index Score
Timepoint [38] 0 0
Baseline (Day 1) and Week 30 during pregnancy and Week 4 postpartum
Secondary outcome [39] 0 0
Infant Health-Related Quality of Life Instrument (IQI) Score for Neonate or Infant Overtime
Timepoint [39] 0 0
Weeks 4, 8 and 52

Eligibility
Key inclusion criteria
* Pregnant and an estimated gestational age (GA) (based on ultrasound dating) from Week 13^0/7 to Week 16^6/7 at randomization
* History of severe Hemolytic Disease of the Fetus and Newborn (HDFN) in a prior pregnancy defined as:

1. documented fetal anemia, or received greater than or equal to (>=)1 IUT as a result of HDFN or
2. 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 laboratory values within the study protocol-specified parameters: a) albumin, >=2.6 grams (g) per deciliter (g/dL), international system (SI): >=26 gram per liter (g/L); 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
* Otherwise healthy on the basis of physical examination, medical history, vital signs, 12-lead ECG, and clinical laboratory tests performed at screening.
Minimum age
18 Years
Maximum age
45 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
* Currently pregnant with a multiple gestation (twins or more)
* Evidence of fetal anemia prior to randomization in the current 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
* 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
* 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 (IVIg), 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 laboratory values during screening
* 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Mater Hospital Brisbane - South Brisbane
Recruitment hospital [2] 0 0
Liverpool Hospital - Sydney
Recruitment postcode(s) [1] 0 0
4101 - South Brisbane
Recruitment postcode(s) [2] 0 0
2170 - Sydney
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Illinois
Country [2] 0 0
United States of America
State/province [2] 0 0
North Carolina
Country [3] 0 0
United States of America
State/province [3] 0 0
Texas
Country [4] 0 0
Argentina
State/province [4] 0 0
Buenos Aires
Country [5] 0 0
Argentina
State/province [5] 0 0
Ciudad Autonoma Buenos Aires
Country [6] 0 0
Belgium
State/province [6] 0 0
Bruxelles
Country [7] 0 0
Belgium
State/province [7] 0 0
Leuven
Country [8] 0 0
Brazil
State/province [8] 0 0
Belo Horizonte
Country [9] 0 0
Brazil
State/province [9] 0 0
Goiania
Country [10] 0 0
Brazil
State/province [10] 0 0
Recife
Country [11] 0 0
Brazil
State/province [11] 0 0
Rio de Janeiro
Country [12] 0 0
Brazil
State/province [12] 0 0
Sao Paulo
Country [13] 0 0
Germany
State/province [13] 0 0
Giessen
Country [14] 0 0
Israel
State/province [14] 0 0
Petah Tikva
Country [15] 0 0
Israel
State/province [15] 0 0
Ramat Gan
Country [16] 0 0
Japan
State/province [16] 0 0
Fukuoka
Country [17] 0 0
Japan
State/province [17] 0 0
Gifu
Country [18] 0 0
Japan
State/province [18] 0 0
Sendai
Country [19] 0 0
Netherlands
State/province [19] 0 0
Leiden
Country [20] 0 0
Spain
State/province [20] 0 0
Barcelona
Country [21] 0 0
Spain
State/province [21] 0 0
Madrid
Country [22] 0 0
Spain
State/province [22] 0 0
Sevilla
Country [23] 0 0
United Kingdom
State/province [23] 0 0
Birmingham
Country [24] 0 0
United Kingdom
State/province [24] 0 0
Manchester
Country [25] 0 0
United Kingdom
State/province [25] 0 0
Oxford

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Janssen Research & Development, LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Janssen Research & Development, LLC Clinical Trial
Address 0 0
Janssen Research & Development, LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Study Contact
Address 0 0
Country 0 0
Phone 0 0
844-434-4210
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
The data sharing policy of the Janssen Pharmaceutical Companies of Johnson \& Johnson is available at www.janssen.com/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
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.janssen.com/clinical-trials/transparency


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.