Clinical trial NCT02287896: Pharmacokinetics and Safety of Roledumab in RhD-negative Pregnant Women Carrying an RhD-positive Foetus
Official title: Pharmacokinetics and Safety of Roledumab, a Fully Human Recombinant Monoclonal Anti-RhD Antibody, in RhD-negative Pregnant Woman Carrying an RhD-positive Foetus: a Phase IIb, Multicenter, Open-label Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rh Disease
Keywords: RhD-negative pregnant woman
anti-RhD antibody
Lead sponsor: Laboratoire français de Fractionnement et de Biotechnologies
Sponsor class: INDUSTRY
First posted: 2014-11-11
Enrollment: 62
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The aim of this study is to assess the pharmacokinetic profile of Roledumab 300μg IM / IV in RhD-negative pregnant women carrying an RhD-positive foetus.

To assess the safety of Roledumab in RhD-negative pregnant women and in RhD-positive fetus and newborns.

In addition the efficacy of Roledumab 300μg IM and IV to prevent RhD alloimmunisation in RhD-negative pregnant women carrying an RhD-positive fetus and the immunogenicity of Roledumab will be assessed.


Eligibility criteria: Inclusion Criteria:

* Signed and dated informed consent form provided by the subject prior to proceeding with any study-related procedure,
* At least 18 years old,
* Pregnancy between 12 and 27 weeks gestational age as confirmed by early ultrasound,
* Pregnant RhD-negative woman carrying an RhD-positive fetus confirmed by a non-invasive fetal RhD genotyping test,
* Negative serology: HIV (1 and 2), hepatitis C and hepatitis B, except for positive results due to vaccinations,
* Covered by healthcare insurance in accordance with local requirements.

Exclusion Criteria:

* RhD allo-immunized subject,
* Positive for ADA test,
* Multiple fetuses,
* Occurrence of a documented potential sensitizing event in this pregnancy before the antenatal IMP administration,
* Prior administration of anti-RhD immunoglobulin during the current pregnancy,
* Known clinically relevant maternal or fetal abnormality (e.g., as determined by ultrasound or genetic testing), such as placenta previa,
* History of anaphylactic or severe systemic reaction to immunoglobulin of any origin,
* Current diagnosis of an immune disease which by itself or its treatment could impair the safety and/or efficacy evaluation of Roledumab in this study. These diseases are: All immune deficiencies, particularly those requiring IV-Ig supplementation or other systemic treatment / connective tissue and autoimmune diseases (e.g., systemic lupus erythematosus, antiphospholipid syndrome, Sjögren's syndrome, rheumatoid arthritis, ankylosing spondylarthritis) requiring systemic immunosuppressive treatment / allergic and inflammatory diseases requiring systemic immunosuppressive treatment,
* Clinically significant medical history contraindicating the participation in the study according to the judgment of the Investigator or Sponsor,
* Clinically significant laboratory (hematology, blood chemistry, or urinalysis) parameters,
* For the IM arm only, subject with coagulation disorders contraindicating intramuscular injection (patient will still be considered for the IV arm),
* Transfusion of RhD-positive blood or blood derived products within the 6 months prior to enrolment,
* Anticipated poor compliance with the study procedures,
* Subject within exclusion period further to her participation in a clinical study.

Primary outcomes:
measure: CL/F : Apparent Clearance
timeFrame: IM: Antenatal PK time points at T0, 48h, 120h, 9d, 29d,59d and Posnatal PK time points at TO, 3d,9d, 6 weeks IV: antenal PK time points at T0, 1h, 24h, 48h, 96-120h, 29d, 59d and Postnatal PK time points at T0, 3d, 9d, 6 weeks.
measure: V2/F : Central Volume of Distribution
timeFrame: IM: Antenatal PK time points at T0, 48h, 120h, 9d, 29d,59d and Posnatal PK time points at TO, 3d,9d, 6 weeks IV: antenal PK time points at T0, 1h, 24h, 48h, 96-120h, 29d, 59d and Postnatal PK time points at T0, 3d, 9d, 6 weeks.
measure: t 1/2 : Terminal Half-life
timeFrame: IM: Antenatal PK time points at T0, 48h, 120h, 9d, 29d,59d and Posnatal PK time points at TO, 3d,9d, 6 weeks IV: antenal PK time points at T0, 1h, 24h, 48h, 96-120h, 29d, 59d and Postnatal PK time points at T0, 3d, 9d, 6 weeks.
measure: C Max
timeFrame: for IM:T0, 48h, 120h, 9 days, 29 days, 59 days and for IV T0, 1h, 24h, 48h, 96-120h, 29 days, 59 days
measure: T Max
timeFrame: for IM:T0, 48h, 120h, 9 days, 29 days, 59 days and for IV T0, 1h, 24h, 48h, 96-120h, 29 days, 59 days
measure: T 1/2
timeFrame: for IM:T0, 48h, 120h, 9 days, 29 days, 59 days and for IV: T0, 1h, 24h, 48h, 96-120h, 29 days, 59 days
measure: AUC 0-t
timeFrame: for IM: T0, 48h, 120h, 9 days, 29 days, 59 days and for IV T0, 1h, 24h, 48h, 96-120h, 29 days, 59 days
Secondary outcomes:
Other outcomes:
Locations:
city: Lille
country: France
facility: Jeanne de Flandre Hospital
city: Lyon
country: France
facility: Croix-Rousse Maternity
city: Nantes
country: France
facility: University Hospital Center
city: Paris
country: France
facility: Armand-Trousseau Hospital
city: Paris
country: France
facility: Port-Royal Maternity
city: Poissy
country: France
facility: Poissy-Saint-Germain-en-Laye Hospital
city: Reims
country: France
facility: Maison Blanche Hospital
city: Toulouse
country: France
facility: Paule de Viguier Hospital
Study officials:
affiliation: Nantes University Hospital
name: Norbert WINER, MD
role: PRINCIPAL_INVESTIGATOR
References: