A Phase 3 Study of Nipocalimab in Pregnancies at Risk for Severe Hemolytic Disease of the Fetus and Newborn (HDFN)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Janssen - Cilag International

Participant type

Patients

Age range

18-64 years

Gender

Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

10 Jul 2024 → ongoing

Decision date (initial)

2024-05-06

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Safety, Efficacy, Pharmacokinetic

To evaluate the efficacy of nipocalimab compared with placebo on reducing the risk of fetal anemia with live neonates in pregnant participants at risk for severe HDFN

Conditions and MedDRA coding

Hemolytic Disease of the Fetus and Newborn (HDFN)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

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

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Female, 18 (or the legal age of consent if above 18 in local regions) to 45 years of age, inclusive, at the time of informed consent.
2. Pregnant and an estimated GA (based on ultrasound dating) from Week 13^0/7 and Week 18^6/7 at randomization.
3. History of severe HDFN in a prior pregnancy, defined as documented: a. fetal anemia* s result of HDFN* or fetal hydrops** as a result of HDFN, or received ≥1 IUT as a result of HDFN. *defined as fetal hemoglobin level <0.84 MoM (Section 8.2.1.2). Fetal hemoglobin (g/dL) can be calculated using hematocrit (%)/3. **defined as the presence of ≥2 abnormal fluid collections in the fetus as ascites, plural effusions, pericardial effusion, and generalized skin edema (skin thickness >5 mm. OR b. Fetal loss or neonatal death as a result of HDFN, with maternal alloantibody titers for RhD, Kell, Rhc, RhE, or RhC antigen above the critical levels (anti-Kell ≥4; other ≥16) and evidence of an antigen-positive fetus (When these tests have not been performed as part of regional/local clinical practice, alternative confirmation of HDFN, after consultation with the sponsor, may be considered).
4. During the current pregnancy, presence of maternal alloantibody to RhD, Kell, 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.
5. Evidence of antigen-positivity corresponding to the current maternal alloantibody (RhD, Kell, Rhc, RhE, or RhC) confirmed by non-invasive antigen cffDNA performed at the central laboratory.

Exclusion criteria 5

1. Currently pregnant with a multiple gestation (twins or more).
2. 2.1 Criterion amended per Amendment 6.Evidence of fetal anemia by ultrasound or repeated MCA-PSV ≥1.5 MoM* prior to randomization in the current pregnancy. *In the absence of other evidence of fetal anemia on ultrasound, inability to measure MCA-PSV before GA 14 weeks 0 days, secondary to concerns of safety/accuracy, will not be considered an exclusion.
3. 3.2 Criterion amended per Amendment 6. History of severe preeclampsia prior to GA Week 34 or severe FGR (EFW<3rd percentile, based on local fetal growth normative standards) in a previous pregnancy. Note: for countries where the percentiles are not used in clinical practice, local country measures (standard deviations) equivalent to <3rd percentile may be considered after consultation with the sponsor.
4. Current uncontrolled hypertension.
5. History of myocardial infarction, unstable ischemic heart disease, or stroke.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The proportion of pregnancies that did not result in fetal loss (due to any reason), IUT, hydrops fetalis, or neonatal death (due to any reason) during the neonatal period (through 4 weeks of age or 41 weeks PMA, whichever is later).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Janssen - Cilag International

Sponsor organisation

Janssen - Cilag International

Address

Turnhoutseweg 30

City

Beerse

Postcode

2340

Country

Belgium

Scientific contact point

Organisation

Janssen - Cilag International

Contact name

CTIS Point of Contact

Public contact point

Organisation

Janssen - Cilag International

Contact name

CTIS Point of Contact

Third parties 16

Locations

11 EU/EEA countries · 22 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 263 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

15 submissions — initial application plus substantial / non-substantial modifications