Pharmacokinetics and Safety of Roledumab in RhD-negative Pregnant Women Carrying an RhD-positive Foetus

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

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.

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.