Rh DiseasePhase 2NCT02287896
Pharmacokinetics and Safety of Roledumab in RhD-negative Pregnant Women Carrying an RhD-positive Foetus
A Phase 2 study testing ROLEDUMAB in people with Rh Disease, run by Laboratoire français de Fractionnement et de Biotechnologies at 8 sites in France.
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Rh Disease
- What is being tested?
- ROLEDUMAB
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 62 participants
- Where
- 8 sitesFrance
- Study dates
- Apr 2014to 13 Sep 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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,
Show all 14Show fewer
- 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.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
France8 sites
Jeanne de Flandre Hospital
Lille, 59037
Croix-Rousse Maternity
Lyon, 69317
University Hospital Center
Nantes, 44093
Armand-Trousseau Hospital
Paris, 75012
Port-Royal Maternity
Paris, 75014
Poissy-Saint-Germain-en-Laye Hospital
Poissy, 78303
Maison Blanche Hospital
Reims, 51092
Paule de Viguier Hospital
Toulouse, 31059
About this study
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
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.
- Conditions
- Rh Disease
- Being tested
- ROLEDUMAB
- Keywords
- RhD-negative pregnant woman, anti-RhD antibody
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ROLEDUMABDrug
Also called LFB-R593
See Arm description
| Study group | Role | What they receive |
|---|---|---|
| Roledumab Open-label IM | Experimental | - Planned antenatal prophylaxis: A single dose of 300 µg IM of Roledumab at 28 or 29 weeks of gestation.
- Antenatal prophylaxis following sensitizing events: One or more dose(s) of 300μg IM anti-RhD antibodies (Rhophylac or Roledumab) based on the Kleihauer-test as soon as possible and no later than 72 hours after event occurrence.
- Postnatal prophylaxis: Roledumab should be administered to the mother as soon as possible within 72 hours of delivery of an RhD positive infant.
The postnatal dose must still be given even when antenatal prophylaxis has been administered.
Before Roledumab 300μg IM postnatal administration, a Kleihauer-Betke test will be performed on maternal blood sample taken no earlier than 30 min after delivery in order to determine the volume of foetomaternal hemorrhage (FMH). Receives: Drug: ROLEDUMAB |
| Roledumab Open-label IV | Experimental | - Planned antenatal prophylaxis: A single dose of 300 µg IV of Roledumab at 28 or 29 weeks of gestation.
- Antenatal prophylaxis following sensitizing events: One or more dose(s) of 300μg IV anti-RhD antibodies (Rhophylac or Roledumab) based on the Kleihauer-test as soon as possible and no later than 72 hours after event occurrence.
- Postnatal prophylaxis: Roledumab should be administered to the mother as soon as possible within 72 hours of delivery of an RhD positive infant.
The postnatal dose must still be given even when antenatal prophylaxis has been administered.
Before Roledumab 300μg IV postnatal administration, a Kleihauer-Betke test will be performed on maternal blood sample taken no earlier than 30 min after delivery in order to determine the volume of foetomaternal hemorrhage (FMH). Receives: Drug: ROLEDUMAB |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
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.
Measured: 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.
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.
Measured: 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.
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: for IM: T0, 48h, 120h, 9 days, 29 days, 59 days and for IV T0, 1h, 24h, 48h, 96-120h, 29 days, 59 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2014 (estimated)
- Study startApr 2014
- Primary completion13 Sep 2017
- Study completion13 Sep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Rh DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- Laboratoire français de Fractionnement et de Biotechnologies
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Norbert WINER, MD, Principal investigator, Nantes University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02287896
- Sponsor's protocol ID
- ADNC-1301
- Other IDs
- 2013-000269-35
- Status last verified
- Aug 2019
- First submitted
- 28 Oct 2014
- Last updated
- 13 Jul 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02287896
- Acronym / sponsor ID
- ADNC-1301
- Conditions
- Rh Disease
- Keywords
- RhD-negative pregnant woman, anti-RhD antibody
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- Laboratoire français de Fractionnement et de BiotechnologiesIndustry (pharma, biotech, devices)
- Study start
- Apr 2014
- Primary completion
- 13 Sep 2017 (actual)
- Study completion
- 13 Sep 2017 (actual)
- First posted
- 11 Nov 2014 (estimated)
- Results
- Posted 16 Aug 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Roledumab Open-label IM | Experimental | Drug: ROLEDUMAB- Planned antenatal prophylaxis: A single dose of 300 µg IM of Roledumab at 28 or 29 weeks of gestation. - Antenatal prophylaxis following sensitizing events: One or more dose(s) of 300μg IM anti-RhD antibodies (Rhophylac or Roledumab) based on the Kleihauer-test as soon as possible and no later than 72 hours after event occurrence. - Postnatal prophylaxis: Roledumab should be administered to the mother as soon as possible within 72 hours of delivery of an RhD positive infant. The postnatal dose must still be given even when antenatal prophylaxis has been administered. Before Roledumab 300μg IM postnatal administration, a Kleihauer-Betke test will be performed on maternal blood sample taken no earlier than 30 min after delivery in order to determine the volume of foetomaternal hemorrhage (FMH). |
| Roledumab Open-label IV | Experimental | Drug: ROLEDUMAB- Planned antenatal prophylaxis: A single dose of 300 µg IV of Roledumab at 28 or 29 weeks of gestation. - Antenatal prophylaxis following sensitizing events: One or more dose(s) of 300μg IV anti-RhD antibodies (Rhophylac or Roledumab) based on the Kleihauer-test as soon as possible and no later than 72 hours after event occurrence. - Postnatal prophylaxis: Roledumab should be administered to the mother as soon as possible within 72 hours of delivery of an RhD positive infant. The postnatal dose must still be given even when antenatal prophylaxis has been administered. Before Roledumab 300μg IV postnatal administration, a Kleihauer-Betke test will be performed on maternal blood sample taken no earlier than 30 min after delivery in order to determine the volume of foetomaternal hemorrhage (FMH). |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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,
Key exclusion criteria (14 listed)
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ROLEDUMABAlso: LFB-R593See Arm description | Drug | Roledumab Open-label IM, Roledumab Open-label IV |
Primary outcome
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.
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.
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.
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.
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.
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.
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Norbert WINER, MD principal investigator
Nantes University Hospital
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ROLEDUMAB in people with Rh Disease, run by Laboratoire français de Fractionnement et de Biotechnologies at 8 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jul 2020.