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Completed

NCT Number: NCT02287896

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

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.

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Key information

Conditions

Rh Disease

Age range

18 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Phase 2

Primary location

Jeanne de Flandre Hospital, Lille, France

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

ROLEDUMAB

Drug

See Arm description

Other names: LFB-R593

Primary outcomes

  1. CL/F : Apparent Clearance

    Time frame: 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.

    The parameter was estimated through a population pharmacokinetic model, during which concentration data (ante- and postnatal) obtained after single IM or IV route dose of roledumab.

    All samples (ante- and postnatal samples for IM and IV route) will be used for population PK modeling.

  2. V2/F : Central Volume of Distribution

    Time frame: 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.

    The parameter was estimated through a population pharmacokinetic model, during which concentration data (ante- and postnatal) obtained after single IM or IV route dose of roledumab.

    All samples (ante- and postnatal samples for IM and IV route) will be used for population PK modeling.

  3. t 1/2 : Terminal Half-life

    Time frame: 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.

    The parameter was estimated through a population pharmacokinetic model, during which concentration data (ante- and postnatal) obtained after single IM or IV route dose of roledumab.

    All samples (ante- and postnatal samples for IM and IV route) will be used for population PK modeling.

  4. C Max

    Time frame: for IM:T0, 48h, 120h, 9 days, 29 days, 59 days and for IV T0, 1h, 24h, 48h, 96-120h, 29 days, 59 days

    C max (maximum observed serum concentration) of Roledumab in all ITT subjects enrolled in the IM arm or the IV arm, who had at least one valid PK assessment after the first IMP administration, providing at least one evaluable PK parameter.

    Only samples post-first administration (antenatal samples) will be analyzed by NCA PK analysis for each study arm.

  5. T Max

    Time frame: for IM:T0, 48h, 120h, 9 days, 29 days, 59 days and for IV T0, 1h, 24h, 48h, 96-120h, 29 days, 59 days

    T max (time of the maximum observed plasma concentration) of Roledumab in all ITT subjects enrolled in the IM arm or the IV arm, who had at least one valid PK assessment after the first IMP administration, providing at least one evaluable PK parameter.

    Only samples post-first administration (antenatal samples) will be analyzed by NCA PK analysis for each study arm.

  6. T 1/2

    Time frame: for IM:T0, 48h, 120h, 9 days, 29 days, 59 days and for IV: T0, 1h, 24h, 48h, 96-120h, 29 days, 59 days

    T 1/2 (apparent plasma terminal elimination half-life) of Roledumab in all ITT subjects enrolled in the IM arm or the IV arm, who had at least one valid PK assessment after the first IMP administration, providing at least one evaluable PK parameter.

    Only samples post-first administration (antenatal samples) will be analyzed by NCA PK analysis for each study arm.

  7. AUC 0-t

    Time frame: for IM: T0, 48h, 120h, 9 days, 29 days, 59 days and for IV T0, 1h, 24h, 48h, 96-120h, 29 days, 59 days

    AUC 0-t (area under the concentration-time curve from time 0 to time Tlast) of Roledumab in all ITT subjects enrolled in the IM arm or the IV arm, who had at least one valid PK assessment after the first IMP administration, providing at least one evaluable PK parameter.

    Only samples post-first administration (antenatal samples) will be analyzed by NCA PK analysis for each study arm.

Sponsors and collaborators

Lead sponsor

Laboratoire français de Fractionnement et de Biotechnologies

Industry

Registry information

Official study 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

Important dates

Study start
2014
Primary completion
2017
Study completion
2017
First posted
Nov 11, 2014
Registry last updated
Jul 13, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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