Pharmacokinetics and Safety of Roledumab in RhD-negative Pregnant Women Carrying an RhD-positive Foetus
Condition: Rh Disease
Intervention: ROLEDUMAB
Intervention description: See Arm description
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 62.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: RhD-negative pregnant woman; anti-RhD antibody

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.