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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03842189




Registration number
NCT03842189
Ethics application status
Date submitted
7/02/2019
Date registered
15/02/2019
Date last updated
23/05/2024

Titles & IDs
Public title
A Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of M281 Administered to Pregnant Women at High Risk for Early Onset Severe Hemolytic Disease of the Fetus and Newborn (HDFN)
Scientific title
A Multicenter, Open-label Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of M281 Administered to Pregnant Women at High Risk for Early Onset Severe Hemolytic Disease of the Fetus and Newborn (HDFN)
Secondary ID [1] 0 0
2017-004958-42
Secondary ID [2] 0 0
CR108980
Universal Trial Number (UTN)
Trial acronym
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(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - M281

Experimental: M281 -


Treatment: Drugs: M281
Participants will receive once weekly intravenous (IV) infusions of M281
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Adverse Events (AEs)
Timepoint [1] 0 0
From signing of informed consent up to approximately 24 weeks post-delivery for mothers; up to approximately 96 weeks post birth for neonates
Primary outcome [2] 0 0
Number of Participants With Live Birth at or After Gestational Age (GA) Week 32 and no Intrauterine Transfusion (IUT) Throughout Their Entire Pregnancy
Timepoint [2] 0 0
Up to approximately GA Week 37
Secondary outcome [1] 0 0
Number of Participants With live Birth
Timepoint [1] 0 0
Up to approximately GA Week 37
Secondary outcome [2] 0 0
Number of Participants at GA Week 24 Without an IUT
Timepoint [2] 0 0
GA Week 24
Secondary outcome [3] 0 0
Gestational age at First IUT
Timepoint [3] 0 0
Up to approximately GA Week 37
Secondary outcome [4] 0 0
Number of IUTs Required
Timepoint [4] 0 0
Up to approximately GA Week 37
Secondary outcome [5] 0 0
Gestational age at Delivery
Timepoint [5] 0 0
Up to approximately GA Week 37
Secondary outcome [6] 0 0
Number of Participants With Fetal Hydrops
Timepoint [6] 0 0
Up to approximately 24 weeks post birth
Secondary outcome [7] 0 0
Number of Neonates Requiring Phototherapy
Timepoint [7] 0 0
Up to approximately 24 weeks post birth
Secondary outcome [8] 0 0
Number of Neonates Requiring Exchange transfusions
Timepoint [8] 0 0
Up to approximately 24 weeks post birth
Secondary outcome [9] 0 0
Number of Days of Postnatal Phototherapy Required by Neonate
Timepoint [9] 0 0
Up to approximately 24 weeks post birth
Secondary outcome [10] 0 0
Number of Neonates Requiring Simple Transfusions in the First 12 weeks of Life
Timepoint [10] 0 0
Up to 12 weeks post birth
Secondary outcome [11] 0 0
Number of Simple Transfusions Required by Neonate in the First 12 weeks of Life
Timepoint [11] 0 0
Up to 12 weeks post birth
Secondary outcome [12] 0 0
Percentage of Maternal Fc Receptor (FcRn) Receptor Occupancy (RO)
Timepoint [12] 0 0
GA Week 14 to approximately GA Week 36
Secondary outcome [13] 0 0
Maternal Levels of Total Immunoglobulin G (IgG)
Timepoint [13] 0 0
GA Week 14 to approximately GA Week 36
Secondary outcome [14] 0 0
Maternal Levels of Alloantibodies
Timepoint [14] 0 0
GA Week 14 to approximately GA Week 36
Secondary outcome [15] 0 0
Mean Concentration of M281 in Maternal Participants
Timepoint [15] 0 0
GA Week 14 to approximately GA Week 36

Eligibility
Key inclusion criteria
- Approximately 15 eligible participants and their offspring will be enrolled

- Each participant must meet all of the following criteria to be enrolled in the study:

- Female and greater than or equal to (>=)18 years of age

- Pregnant to an estimated gestational age of between 8 up to 14 weeks

- A previous pregnancy with a gestation that included at least one of the following
prior to week 24 gestation:

- Severe fetal anemia, defined as hemoglobin less than or equal to (<=) 0.55 multiples
of the median (MOM) for gestational age

- Fetal hydrops with peak systolic velocity MOM >=1.5

- Stillbirth with fetal or placental pathology indicative of hemolytic disease of the
fetus and newborn (HDFN)

- Maternal alloantibody titers for anti-D of >=32, or anti-Kell titers >=4

- Free fetal deoxyribonucleic acid consistent with an antigen-positive fetus (blood
sample taken from mother)

- Maternal evidence for Immunity to measles mumps, rubella, and varicella, as documented
by serologies performed during Screening. If initial serologies are borderline or
negative, they may be repeated at a second lab. Alternatively, vaccination records can
be used to support evidence of immunity.

- Screening immunoglobulin G and albumin levels within the laboratory normal range for
gestational age of pregnancy

- Willing to receive standard of care with intrauterine transfusion if clinically
indicated

- Agree to receive recommended vaccinations per local standard of care for both mother
and child throughout the course of the study

- It is recommended that patients are up-to-date on age-appropriate vaccinations prior
to screening as per routine local medical guidelines. For study patients who received
locally-approved (and including emergency use-authorized) Coronavirus Disease 2019
(COVID-19) vaccines recently prior to study entry, follow applicable local vaccine
labelling, guidelines, and standard of care for pregnant women receiving
immune-targeted therapy when determining an appropriate interval between vaccination
and study enrollment
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
- Currently pregnant with multiples (twins or more)

- Pre-eclampsia In current pregnancy or history of pre-eclampsia in a previous pregnancy

- Gestational hypertension in the current pregnancy

- Current unstable hypertension

- History of severe or recurrent pyelonephritis, 4 or more lower urinary tract
infections in the past year or in a previous pregnancy

- History of genital herpes infection

- Active Infection at Screening or Baseline with Coxsackie, syphilis, cytomegalovirus,
toxoplasmosis or herpes simplex 1 or 2, as evidenced by clinical signs and symptoms
(evidence for prior Infection or exposure, but without clinical signs and symptoms of
active infection is acceptable)

- Active infection with tuberculosis as evidenced by positive QuantiFERON-tuberculosis
testing

- Requires treatment with corticosteroids or immunosuppression for disorders unrelated
to the pregnancy (use of low-potency topical corticosteroids or intra-articular
corticosteroids is permitted)

- Has received or is expected to receive any live virus or bacterial vaccine within 12
weeks prior to screening or has a known need to receive a live vaccine while receiving
nipocalimab, or within 12 weeks after the last administration of nipocalimab in the
study or has received Bacille Calmett-Guérin (BCG) vaccine within 1 year prior to the
first administration of nipocalimab

- Currently receiving an antibody-based drug or an Fc-fusion protein drug

- Received plasmapheresis and/or intravenous immunoglobulin during the current pregnancy
for treatment of HDFN

- COVID-19 infection: during the 6 weeks prior to baseline (regardless of vaccination
status), have had any of: a) confirmed severe acute respiratory syndrome
coronavirus(-2) (SARS-CoV-2) (COVID-19) infection (test positive), or; b) suspected
SARS-CoV-2 infection (clinical features without documented test results), or; c) close
contact with a person with known or suspected SARS-CoV-2 infection. Exception: may be
included with a documented negative result for a validated SARSCoV-2 test: obtained at
least 2 weeks after conditions a), b), c) above (timed from resolution of key clinical
features if present, example fever, cough, dyspnea) and; with absence of all
conditions a), b), c) above during the period between the negative test result and the
baseline study visit

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
5/04/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
8/11/2024
Actual
Sample size
Target
Accrual to date
Final
14
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Liverpool Hospital - Sydney
Recruitment postcode(s) [1] 0 0
2170 - Sydney
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
New York
Country [3] 0 0
United States of America
State/province [3] 0 0
Ohio
Country [4] 0 0
United States of America
State/province [4] 0 0
Oregon
Country [5] 0 0
United States of America
State/province [5] 0 0
Pennsylvania
Country [6] 0 0
United States of America
State/province [6] 0 0
Texas
Country [7] 0 0
United States of America
State/province [7] 0 0
Utah
Country [8] 0 0
Belgium
State/province [8] 0 0
Leuven
Country [9] 0 0
Canada
State/province [9] 0 0
British Columbia
Country [10] 0 0
Canada
State/province [10] 0 0
Ontario
Country [11] 0 0
Canada
State/province [11] 0 0
Quebec
Country [12] 0 0
Germany
State/province [12] 0 0
Giessen
Country [13] 0 0
Netherlands
State/province [13] 0 0
Leiden
Country [14] 0 0
Spain
State/province [14] 0 0
Granada
Country [15] 0 0
Sweden
State/province [15] 0 0
Stockholm
Country [16] 0 0
United Kingdom
State/province [16] 0 0
Birmingham
Country [17] 0 0
United Kingdom
State/province [17] 0 0
London

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

Ethics approval
Ethics application status

Summary
Brief summary
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 Severe Hemolytic Disease
of the Fetus and Newborn (EOS-HDFN). The effectiveness of the investigational drug M281 will
be measured by looking at the percentage of participants with live birth at or after
gestational age (GA) 32 weeks and without a need for an intrauterine transfusion (IUT)
throughout their entire pregnancy.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03842189
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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03842189