Clinical trial • Phase II • Immunology | Rare Disease

RILIPRUBART for Antibody-mediated rejection (AMR) | Transplant rejection

Phase II trial of RILIPRUBART for Antibody-mediated rejection (AMR) | Transplant rejection.

Overview

Trial Therapeutic Area
Immunology | Rare Disease
Trial Disease
Antibody-mediated rejection (AMR) | Transplant rejection
Trial Stage
Phase II
Drug Modality
Peptide/protein/enzyme

Key dates

Initial CTIS Submission Date
14-05-2024
First CTIS Authorization Date
12-06-2024

Trial design

Randomised, open-label, soc (standard of care) arm as comparator; bivv020 + soc interventional arm. no specific bivv020 dosing schedule is provided in the available data (dose unit mg/kg; max total amount listed as 50 mg/kg; max treatment period listed as 49 with time unit code 2).-controlled, crossover Phase II trial across 14 sites in Sweden, Germany, Spain and others.

Randomised
Yes
Open Label
Yes
Comparator
SOC (standard of care) arm as comparator; BIVV020 + SOC interventional arm. No specific BIVV020 dosing schedule is provided in the available data (dose unit mg/kg; max total amount listed as 50 mg/kg; max treatment period listed as 49 with time unit code 2).
Crossover
Yes
Target Sample Size
40

Eligibility

Recruits 40 Vulnerable population flag is selected for the trial. Subject information and informed consent forms are provided for adult patients (multiple adult ICFs listed). ICFs and related materials are available in multiple languages (English, German, Spanish, French, Italian, Swedish). No specific information on assent or consent procedures for minors is provided in the available data..

Vulnerable Population
Vulnerable population flag is selected for the trial. Subject information and informed consent forms are provided for adult patients (multiple adult ICFs listed). ICFs and related materials are available in multiple languages (English, German, Spanish, French, Italian, Swedish). No specific information on assent or consent procedures for minors is provided in the available data.

Inclusion criteria

  • {"criterion_text":"- Participant intended to receive SOC therapy per Investigator’s judgment and local practice. Cohort A: Participants with chronic kidney disease who will receive a kidney transplant from a living or deceased donor . Cohort B: Participants who are kidney transplant recipients diagnosed with active AMR. BMI ≤ 40 kg/m2. Contraceptive use by women during the treatment period, and for at least 49 weeks after the last administration of IMP (BIVV020 + SOC arm participant) or last treatment period visit (SOC arm participant). Contraceptive use by men during the treatment period, and for at least 49 weeks after the last administration of IMP (BIVV020 + SOC arm participant) or last treatment period visit (SOC arm participant).","number_of_inclusion_criteria":5}

Exclusion criteria

  • {"criterion_text":"- Participants who are ABO incompatible with their donors.\n- Participants with known active ongoing infection as per below: a)\tPositive HIV. b)\tPositive HBV. c)\tHCV with detectable HCV RNA. d)\tWithin 4 weeks of first study intervention: any serious infection, or any active bacterial infection i, or any other infection which is clinically significant in the option of the Investigator, unless it can be confirmed that infection was cleared at least 3 days prior to first study intervention\n- History of active tuberculosis (TB) regardless of treatment.\n- Participants with clinical diagnosis of systemic lupus erythematosus (SLE).\n- Prior treatment with complement system inhibitor within 5 times the half-life.\n- Current enrollment in any other clinical study where the last investigational study treatment administration was within 5 half-lives from study intervention initiation."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Cohort A: Treatment failure rate","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Cohort B: AMR resolution rate","definition_or_measurement_approach":""}

Secondary endpoints

  • {"endpoint_text":"- Cohort A: Treatment failure rate","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Cohort B: AMR resolution rate","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Change in renal function from baseline per central laboratory assessment of estimated glomerular filtration rate (eGFR) from serum creatinine using Modification of Diet in Renal Disease equation (MDRD)","definition_or_measurement_approach":"Central laboratory assessment of eGFR calculated from serum creatinine using the MDRD equation (change from baseline)."}
  • {"endpoint_text":"- Change in renal function from baseline per central laboratory assessment using protein: creatinine ratio","definition_or_measurement_approach":"Central laboratory assessment of protein:creatinine ratio (change from baseline)."}
  • {"endpoint_text":"- Change in allograft histopathology Banff score","definition_or_measurement_approach":"Change in allograft histopathology assessed using the Banff scoring criteria."}
  • {"endpoint_text":"- Graft survival as predicted by iBOX","definition_or_measurement_approach":"Graft survival prediction evaluated using the iBOX prediction tool."}
  • {"endpoint_text":"- Assessment of adverse events (AEs)","definition_or_measurement_approach":"Evaluation and recording of adverse events experienced by participants."}
  • {"endpoint_text":"- Change in systemic lupus erythematosus (SLE) panel","definition_or_measurement_approach":"Change in SLE laboratory panel parameters from baseline."}
  • {"endpoint_text":"- Plasma exposure of BIVV020 assessing pharmacokinetic parameter Cmin","definition_or_measurement_approach":"Measurement of plasma exposure of BIVV020 with assessment of the pharmacokinetic parameter Cmin."}
  • {"endpoint_text":"- Plasma exposure of BIVV020 assessing pharmacokinetic parameter AUC","definition_or_measurement_approach":"Measurement of plasma exposure of BIVV020 with assessment of the pharmacokinetic parameter AUC."}
  • {"endpoint_text":"- Number of participants with anti-BIVV020 antibodies","definition_or_measurement_approach":"Determination and counting of participants who develop anti-BIVV020 antibodies."}

Recruitment

Planned Sample Size
40
Recruitment Window Months
53
Consent Approach
Informed consent is obtained from adult participants. Subject information and informed consent forms are provided for adult patients and are available in multiple languages (English, German, Spanish, French, Italian, Swedish). Documents include pre-screening and partner/pregnancy information forms. No information on assent procedures for minors is provided.

Geography

Total Number Of Sites
14
Total Number Of Participants
40

Sweden

Earliest CTIS Part Ii Submission Date
30-05-2024
Latest Decision Or Authorization Date
12-06-2024
Processing Time Days
13
Number Of Sites
2
Number Of Participants
4

Sites

Site Name
Uppsala University Hospital
Department Name
Transplantationsmottagningen
Principal Investigator Name
Tomas Lorant
Principal Investigator Email
tomas.lorant@surgsci.uu.se
Contact Person Name
Tomas Lorant
Contact Person Email
tomas.lorant@surgsci.uu.se
Site Name
Karolinska University Hospital
Department Name
Transplantationsmottagningen
Principal Investigator Name
Lars Wennberg
Principal Investigator Email
lars.wennberg@regionstockholm.se
Contact Person Name
Lars Wennberg

Germany

Earliest CTIS Part Ii Submission Date
30-05-2024
Latest Decision Or Authorization Date
14-06-2024
Processing Time Days
15
Number Of Sites
1
Number Of Participants
7

Sites

Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
Nephrologie/Intensivmedizin
Principal Investigator Name
Fabian Halleck
Principal Investigator Email
fabian.halleck@charite.de
Contact Person Name
Fabian Halleck
Contact Person Email
fabian.halleck@charite.de

Spain

Earliest CTIS Part Ii Submission Date
30-05-2024
Latest Decision Or Authorization Date
12-06-2024
Processing Time Days
13
Number Of Sites
2
Number Of Participants
8

Sites

Site Name
Hospital Universitario 12 De Octubre
Department Name
Servicio de Nefrología
Principal Investigator Name
Amado Andres Belmonte
Principal Investigator Email
amado.andres@salud.madrid.org
Contact Person Name
Amado Andres Belmonte
Contact Person Email
amado.andres@salud.madrid.org
Site Name
Hospital Universitari Vall D Hebron
Department Name
Servicio de Nefrología
Principal Investigator Name
Oriol BESTARD MATAMOROS
Principal Investigator Email
oriol.bestard@vallhebron.cat
Contact Person Name
Oriol BESTARD MATAMOROS
Contact Person Email
oriol.bestard@vallhebron.cat

France

Earliest CTIS Part Ii Submission Date
30-05-2024
Latest Decision Or Authorization Date
17-06-2024
Processing Time Days
18
Number Of Sites
5
Number Of Participants
13

Sites

Site Name
Centre Hospitalier Universitaire De Bordeaux
Department Name
Service de Nephrologie-Transplantation-Dialyse-Aphérèses
Principal Investigator Name
Pierre Merville
Principal Investigator Email
pierre.merville@chu-bordeaux.fr
Contact Person Name
Pierre Merville
Site Name
Hospital Foch
Department Name
Service de Nephrologie Dialyse et Transplantation Rénale
Principal Investigator Name
Alexandre Hertig
Principal Investigator Email
a.hertig@hopital-foch.com
Contact Person Name
Alexandre Hertig
Contact Person Email
a.hertig@hopital-foch.com
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Service de Néphrologie-Transplantations
Principal Investigator Name
Carmen Lefaucher
Principal Investigator Email
carmen.lefaucheur@aphp.fr
Contact Person Name
Carmen Lefaucher
Contact Person Email
carmen.lefaucheur@aphp.fr
Site Name
Centre Hospitalier Universitaire De Toulouse
Department Name
Service de Nephrologie et Transplantation
Principal Investigator Name
Nassim Kamar
Principal Investigator Email
kamar.n@chu-toulouse.fr
Contact Person Name
Nassim Kamar
Contact Person Email
kamar.n@chu-toulouse.fr
Site Name
Assistance Publique Hopitaux De Paris (Creteil)
Department Name
Service de Nephrologie et Transplantation
Principal Investigator Name
Philippe Grimbert
Principal Investigator Email
philippe.grimbert@aphp.fr
Contact Person Name
Philippe Grimbert
Contact Person Email
philippe.grimbert@aphp.fr

Italy

Earliest CTIS Part Ii Submission Date
30-05-2024
Latest Decision Or Authorization Date
01-07-2024
Processing Time Days
32
Number Of Sites
4
Number Of Participants
8

Sites

Site Name
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
Department Name
Unita Operativa di Nefrologia
Principal Investigator Name
Nicola Bossini
Principal Investigator Email
bossini-nicola@libero.it
Contact Person Name
Nicola Bossini
Contact Person Email
bossini-nicola@libero.it
Site Name
Azienda Ospedaliera Ospedale Niguarda Ca Granda
Department Name
Struttura Complessa Nefrologia
Principal Investigator Name
Enrico Minetti
Principal Investigator Email
enrico.minetti@ospedaleniguarda.it
Contact Person Name
Enrico Minetti
Site Name
Azienda Ospedaliero-Universitaria Di Bologna IRCCS
Department Name
Unita di Nefrologia, Dialisi e Trapianto di Rene - PAD 15
Principal Investigator Name
Gaetano La Mann
Principal Investigator Email
gaetano.lamanna@unibo.it
Contact Person Name
Gaetano La Mann
Contact Person Email
gaetano.lamanna@unibo.it
Site Name
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Department Name
Unita Operativa Complessa Nefrologia
Principal Investigator Name
Giuseppe Grandaliano
Principal Investigator Email
giuseppe.grandaliano@policlinicogemelli.it
Contact Person Name
Giuseppe Grandaliano

Sponsor

Primary sponsor

Full Name
Sanofi-Aventis Recherche & Developpement
Organisation Type
Pharmaceutical company
Country Of Registered Address
France

Contract research organisations

Name
Pharmaceutical Product Development LLC
Responsibilities
sponsorDuties codes: [4]
Name
PPD Development LP
Responsibilities
sponsorDuties codes: [4]
Name
Endpoint Clinical Inc.
Responsibilities
sponsorDuties codes: [3]
Name
Cognizant Technology Solutions India Private Limited
Responsibilities
sponsorDuties codes: [6]

Third parties

  • {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"Azenta Germany GmbH","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"sponsorDuties codes: [14]","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"Discovery Life Sciences Biomarker Services GmbH","duties_or_roles":"sponsorDuties codes: [15]; value: Central Medical Reading or Imaging Reading","organisation_type":"Pharmaceutical company"}
  • {"country":"India","full_name":"Cognizant Technology Solutions India Private Limited","duties_or_roles":"sponsorDuties codes: [6]","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
  • {"country":"Italy","full_name":"Depo-pack S.r.l.","duties_or_roles":"sponsorDuties codes: [14]","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"ESMS Global Limited","duties_or_roles":"sponsorDuties codes: [15]; value: Centralized 24-Hour Emergency System: eSMS","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Northwestern University","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Educational Institution"}
  • {"country":"Germany","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"sponsorDuties codes: [14]","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":"sponsorDuties codes: [3]","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
riliprubart
Active Substance
RILIPRUBART
Modality
Peptide/protein/enzyme
Routes Of Administration
Subcutaneous
Route
Subcutaneous
Maximum Dose
50 mg/kg
Combination Treatment
Yes

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