Clinical Trials Register

Summary
EudraCT Number:	2021-000010-41
Sponsor's Protocol Code Number:	ACT17012
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-08-30
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2021-000010-41

A.3

Full title of the trial

A multi-cohort, randomized, Phase 2, open-label study to assess the preliminary efficacy, safety, and pharmacokinetics of BIVV020 for prevention and treatment of antibody-mediated rejection in adult kidney transplant recipients

Estudio en fase II, abierto, aleatorizado y de múltiples cohortes para evaluar la eficacia, la seguridad y la farmacocinética preliminares de BIVV020 para la prevención y el tratamiento del rechazo mediado por anticuerpos en adultos receptores de trasplante renal.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

BIVV020 in prevention and treatment of antibody-mediated rejection (AMR)

BIVV020 para la prevención y el tratamiento del rechazo mediado por anticuerpos (RMA)

A.4.1

Sponsor's protocol code number

ACT17012

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1267-2612

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Sanofi-Aventis Recherche & Développement
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Sanofi-Aventis Recherche & Développement
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Sanofi-Aventis, S.A
B.5.2	Functional name of contact point	Unidad de Estudios Clínicos
B.5.3	Address:
B.5.3.1	Street Address	C/ Josep Pla 2, 4ª planta
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08019
B.5.3.4	Country	Spain
B.5.4	Telephone number	+3493485 94 00
B.5.6	E-mail	es-reg-estudiosclinicos@sanofi.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.2	Product code	BIVV020
D.3.4	Pharmaceutical form	Solution for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not assigned
D.3.9.2	Current sponsor code	BIVV020
D.3.9.3	Other descriptive name	BIVV020
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	150
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Yes
D.3.11.13.1	Other medicinal product type	BIVV020 is a humanized monoclonal antibody that binds to and selectively inhibits the activated form of human serine protease complement component 1, s subcomponent (C1s)

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Antibody-mediated rejection in adult kidney transplant recipients

Rechazo mediado por anticuerpos en adultos receptores de trasplante renal

E.1.1.1

Medical condition in easily understood language

Renal disease.

Enfermedad renal.

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10064683
E.1.2	Term	Antibody-mediated rejection
E.1.2	System Organ Class	100000004870

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

• Cohort A: To evaluate the efficacy of BIVV020 in prevention of AMR
• Cohort B: To evaluate the efficacy of BIVV020 in treatment of AMR

•Cohorte A: evaluar la eficacia de BIVV020 en la prevención del RMA
•Cohorte B: evaluar la eficacia de BIVV020 en el tratamiento del RMA activo

E.2.2

Secondary objectives of the trial

• To assess the overall efficacy of BIVV020 in prevention or treatment of AMR;
• To characterize the safety and tolerability of BIVV020 in kidney transplant participants;
• To characterize the pharmacokinetic (PK) profile of BIVV020 in kidney transplant participants;
• To evaluate the immunogenicity of BIVV020.

•Evaluar la eficacia general de BIVV020 en la prevención o el tratamiento del RMA
•Caracterizar la seguridad y tolerabilidad de BIVV020 en participantes con trasplante de riñón
•Caracterizar el perfil farmacocinético (FC) de BIVV020 en participantes con trasplante de riñón
•Evaluar la inmunogenicidad de BIVV020.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- 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 to whom they are sensitized, and/or required desensitization prior to transplantation.
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 52 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 52 weeks after the last administration of IMP (BIVV020 + SOC arm participant) or last treatment period visit (SOC arm participant).
- 18-75 years old at the time of consent.

Participantes propuestos para recibir el Estándar de Tratamiento (ET) a juicio investigador y según práctica local.
•Cohorte A : Participantes con enfermedad renal crónica candidatos a trasplante de riñón de donante vivo o fallecido al que estén sensibilzados y/o que requieran desensibilización antes del trasplante
•Cohorte B : Participantes receptores de trasplante renal con RMA activo
•Índice de masa corporal (IMC) ≤40 kg/m2BMI ≤ 40 kg/m2.
•El uso de anticonceptivos por parte de mujeres durante el período de tratamiento y hasta al menos 52 semanas después de la última administración del Medicamento en Investigación MI (grupo de BIVV020 + ET) o la última visita del período de tratamiento (grupo de ET):
•El uso de anticonceptivos por parte de hombres durante el período de tratamiento y hasta al menos 52 semanas después de la última administración del Medicamento en Investigación MI (grupo de BIVV020 + ET) o la última visita del período de tratamiento (grupo de ET).
•18-75 años en el momento de firmar el consentimiento.

E.4

Principal exclusion criteria

- Participants are excluded from the study if any of the following criteria apply:
- Participants who are ABO incompatible with their donors.
- Participants with known active ongoing infection as per below:
a) Positive HIV.
b) Positive HBV.
c) HCV with detectable HCV RNA.
d) Within 4 weeks of first study intervention: any serious infection, or infection requiring antibiotic treatment against an identified or suspected bacterial pathogen.
- History of active tuberculosis (TB) regardless of treatment.
- Participants with clinical diagnosis of systemic lupus erythematosus (SLE).
- Prior treatment with complement system inhibitor within 5 times the half-life.
- Current enrollment in any other clinical study where the last investigational study treatment administration was within 5 half-lives from study intervention initiation.

• Participantes que tengan un grupo sanguíneo ABO incompatible con el de los donantes.
• Participantes con algunas de las siguientes infecciones activas conocidas en curso:
a) VIH positivo.
b) VHB positivo.
c) VHC
d) En las 4 semanas anteriores al primer tratamiento del estudio: cualquier infección
grave o que requiera tratamiento antibiótico contra un patógeno bacteriano
identificado o sospechoso.
• Antecedentes de tuberculosis (TB) activa independientemente del tratamiento.
• Participantes con diagnóstico clínico de lupus eritematoso sistémico (LES).
• Haber recibido tratamiento previo con algún medicamento en investigación (ihibidor del complemento) que no tenga autorización de comercialización en cualquier región en las 5 semividas anteriores al inicio del tratamiento del estudio
• Estar incluidos actualmente en algún otro estudio clínico en el que la última administración del tratamiento en investigación fuese en las 5 semividas anteriores al inicio del tratamiento del estudio.

E.5 End points

E.5.1

Primary end point(s)

1) Cohort A: Treatment failure rate
Defined as the proportion of participants meeting at least one of the following criteria:
-Biopsy-proven active AMR as per Banff Criteria 2019 as per central pathology assessment,
-Graft loss.

2) Cohort B: AMR resolution rate
Defined as the proportion of participants with post-treatment biopsy not fulfilling active AMR diagnosis criteria as per Banff Criteria 2019 as per central pathology assessment.

1) Cohorte A: La tasa de fallo del tratamiento
Defined as the proportion of participants meeting at least one of the following criteria:
Definida como la proporción de participantes que cumplen al menos uno de los siguientes criterios
-RMA activo demostrado mediante biopsia según los criterios de Banff 2019 conforme a la evaluación anatomopatológica central
-Pérdida del injerto

2) Cohorte B: Tasa de resolución del RMA
Definida como la proporción de participantes con biopsia después del tratamiento que no cumplen los criterios diagnósticos de RMA activo según los criterios de Banff 2019 y conforme a la evaluación anatomopatológica central

E.5.1.1

Timepoint(s) of evaluation of this end point

1)Day 1 up to 49 weeks

2) Day 1 up to 49 weeks

at the time of the 13, 25 and 49 week visits.

1) En el momento de día 1 hasta la semana 49.

2) En el momento de día 1 hasta la semana 49.

en el momento de las visitas de las semanas 13, 25 y 49,

E.5.2

Secondary end point(s)

1) Cohort A: Treatment failure rate
as per local assessment using Banff criteria 2019

2) Cohort B: AMR resolution rate
as per local assessment using Banff criteria 2019

3) Change in renal function from baseline
as per central laboratory assessment (eGFR MDRD, serum creatinine, protein: creatinine ratio)

4) Change in histopathology from baseline

5) Graft survival as predicted by iBOX

6) Assessment of adverse events (AEs)
Number of participants with adverse events (AEs)

7) Change in systemic lupus erythematosus (SLE) panel

8) Plasma exposure of BIVV020
PK parameters include, but may not be limited to Cmin and AUCss

9) Number of participants with anti-BIVV020 antibodies
Percent of participants developed drug-induced ADAs

1. Cohorte A: tasa de fallo del tratamiento según los criterios de Banff 2019 de acuerdo con la evaluación local
2. Cohorte B: tasa de resolución del RMA según los criterios de Banff 2019 de acuerdo con la evaluación local
3. Cambio en la función renal desde el inicio según la evaluación del laboratorio central (eGFR con la ecuación MDRD, creatinina sérica, cociente proteína/creatinina)
4. Cambio en la histopatología desde el inicio
5. Supervivencia del injerto según lo previsto por iBOX
6. Evaluacion de Acontecimiento Adversos (AEs)
7. Cambio en el perfil analítico del lupus eritematoso sistémico (LES)
8. Exposición plasmática de BIVV020: Caracterizar el perfil farmacocinético (FC) de BIVV020 parámetros que incluirán al menos Cmin and AUCss
9. Evaluar la inmunogenicidad de BIVV020 (Número de participantes con anticuerpos anti-BIVV020): Incidencia de anticuerpos antifármaco (AAF) contra BIVV020 (porcerntaje de pacientes que desarrollan AAF)

E.5.2.1

Timepoint(s) of evaluation of this end point

1)-2)-4)-5) Up to 49 weeks
3)-7)-8)-9) Up to 22 weeks after end of treatment period
6) Up to end of study

1)-2)-4)-5) Hasta la semana 49
3)-7)-8)-9) HASta semana 22 weeks despues del período de tratamiento. of treatment period
6) Hasta fin de estudio

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

France

Germany

Italy

Spain

Sweden

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LSLV

La última visita del último paciente.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2021-10-08

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-10-05

P. End of Trial
P.	End of Trial Status	Ongoing

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