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

Rh Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02287896
• Other study ID #: ADNC-1301
• Secondary ID: 2013-000269-35
• Status: Completed
• Phase: Phase 2
• Start date: April 2014
• Est. completion date: September 13, 2017

Study information

• Verified date: August 2019
• Source: Laboratoire français de Fractionnement et de Biotechnologies
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: September 13, 2017
• Est. primary completion date: September 13, 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Rh Disease

Intervention

Drug:
• ROLEDUMAB
See Arm description

Locations

Country	Name	City	State
France	Jeanne de Flandre Hospital	Lille
France	Croix-Rousse Maternity	Lyon
France	University Hospital Center	Nantes
France	Armand-Trousseau Hospital	Paris
France	Port-Royal Maternity	Paris
France	Poissy-Saint-Germain-en-Laye Hospital	Poissy
France	Maison Blanche Hospital	Reims
France	Paule de Viguier Hospital	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
Laboratoire français de Fractionnement et de Biotechnologies

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CL/F : Apparent Clearance	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.	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.
Primary	V2/F : Central Volume of Distribution	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.	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.
Primary	t 1/2 : Terminal Half-life	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.	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.
Primary	C Max	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.	for IM:T0, 48h, 120h, 9 days, 29 days, 59 days and for IV T0, 1h, 24h, 48h, 96-120h, 29 days, 59 days
Primary	T Max	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.	for IM:T0, 48h, 120h, 9 days, 29 days, 59 days and for IV T0, 1h, 24h, 48h, 96-120h, 29 days, 59 days
Primary	T 1/2	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.	for IM:T0, 48h, 120h, 9 days, 29 days, 59 days and for IV: T0, 1h, 24h, 48h, 96-120h, 29 days, 59 days
Primary	AUC 0-t	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.	for IM: T0, 48h, 120h, 9 days, 29 days, 59 days and for IV T0, 1h, 24h, 48h, 96-120h, 29 days, 59 days