Clinical Trials Register

Summary
EudraCT Number:	2016-001028-80
Sponsor's Protocol Code Number:	ACT14604
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2016-08-02
Trial results	View 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

Belgium - FPS Health-DGM

A.2

EudraCT number

2016-001028-80

A.3

Full title of the trial

Efficacy and safety of SAR156597 in the treatment of diffuse cutaneous Systemic Sclerosis (dcSSc): A randomized, double-blind, placebo-controlled, 24-week, proof of concept study

A.3.1

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

Effectiveness and Safety of SAR156597 in Treating Diffuse Systemic Sclerosis

A.4.1

Sponsor's protocol code number

ACT14604

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1179-4690

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 Belgium
B.5.2	Functional name of contact point	Brigitte De Witte
B.5.3	Address:
B.5.3.1	Street Address	Airport Plaza - Montreal Building, L. Da Vincilaan 19
B.5.3.2	Town/ city	Diegem
B.5.3.3	Post code	1831
B.5.3.4	Country	Belgium
B.5.4	Telephone number	+32 (0)2 710 54 00
B.5.5	Fax number	+32 (0)2 710 56 99
B.5.6	E-mail	contact-us@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	SAR156597
D.3.4	Pharmaceutical form	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	SAR156597
D.3.9.4	EV Substance Code	SUB33159
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	100
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)	No
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	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Powder for solution for injection
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Systemic sclerosis

E.1.1.1

Medical condition in easily understood language

Systemic sclerosis

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10042953
E.1.2	Term	Systemic sclerosis
E.1.2	System Organ Class	100000171021

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate, in comparison with placebo, the efficacy of SAR156597 administered subcutaneously on skin fibrosis in patients with dcSSc.

E.2.2

Secondary objectives of the trial

-To evaluate the efficacy of SAR156597 compared to placebo on physical/functional disability in patients with dcSSc.
-To evaluate the efficacy of SAR156597 compared to placebo on respiratory function in patients with dcSSc.
-To evaluate the safety profile of SAR156597 compared to placebo in patients with dcSSc.
-To evaluate the potential for immunogenicity (anti-drug antibodies [ADA] response) of SAR156597 in patients with dcSSc.
-To evaluate the pharmacokinetics (PK) (trough plasma concentrations) of SAR156597
administered subcutaneously.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

-Systemic Sclerosis according to the American College of Rheumatology/The European League against Rheumatism (ACR/EULAR) 2013 criteria.
-Diffuse cutaneous form of SSc according to Leroy’s criteria.
-Able and willing to sign the written informed consent form with comprehension of its contents and comply with the requirements of the study protocol.

E.4

Principal exclusion criteria

-Age <18 years of age.
-Disease duration of >36 months from time of first non-Raynaud’s phenomenon manifestation.
-mRSS <10 or >35 at screening and baseline visits.
-History of vasculitis, active or in remission
-Diagnosis of connective tissue disease (other than SSc) or overlap syndrome (eg, polymyositis/SSc).
-Positive Human Immunodeficiency Virus (HIV) serology or a known history of HIV infection, active or in remission
-Abnormal hepatitis B and/or hepatitis C tests indicative of active or chronic infection ((refer to protocol)
-Positive or 2 confirmed indeterminate Quantiferon-TB Gold tests at screening
-Serious infection (eg, pneumonia, pyelonephritis) within 4 weeks of screening, infection requiring hospitalization or intravenous antibiotics within 4 weeks of screening or chronic bacterial infection (eg, osteomyelitis).
-History of anaphylaxis to any biologic therapy.
-Evidence of any clinically significant, severe or unstable, acute or chronically progressive, uncontrolled infection or medical condition (eg, cerebral, cardiac, pulmonary, renal, hepatic, gastrointestinal or neurologic other than SSc or SSc-ILD) or previous, active or pending surgical disorder, or any condition that may affect patient safety in the judgment of the Investigator.
-At screening, the % predicted forced vital capacity (FVC) is ≤75% AND % predicted carbon monoxid diffusing lung capacity (DLCO) after hemoglobin correction is ≤40%
-History of heart failure (including acutely decompensated in the setting of preserved ejection fraction), Left Ventricular Ejection Fraction (LVEF) ≤45%, coronary artery disease, angina, myocardial infarction, ischemic cardiomyopathy and/or hypertrophic cardiomyopathy
-Any prior history of malignancy or active malignancy, including lymphoproliferative diseases (except successfully-treated carcinoma in-situ of the cervix, non-metastatic squamous cell or basal cell carcinoma of the skin) within 5 years prior to baseline.
Ischemic ECG changes (except those NOT supported by the findings of a left heart catheterization performed in the last year within screening) and/or other clinically significant ECG findings (Appendix L) at screening. (All abnormal ECG finding will be reviewed and confirmed by a local cardiologist.)
-High dose steroids (>10 mg/day prednisolone equivalent); or change in steroid dose within 4 weeks prior to screening or during the screening period; or expected changes during the course of the study.
-Previous treatment with rituximab within 12 months prior to screening.
-Previous treatment with bone marrow transplantation, total lymphoid irradiation or ablative ultrahigh dose cyclophosphamide.
-Treatment with high dose immunosuppressive drug (eg, cyclophosphamide >1 mg/kg oral/day or >750 mg IV/month; azathioprine >100 mg/day; methotrexate >15 mg/week; mycophenolate mofetil >2 g/day) within 3 months of screening or change in dose within 4 weeks prior to baseline.
-Treatment with etanercept, cyclosporine A, intravenous immunoglobulin (IVIG), rapamycin, Dpenicillamine, tyrosine kinase inhibitors within 4 weeks of screening or antithymocyte globulin within 6 months of screening.
-Treatment with infliximab, certolizumab, golimumab, abatacept, or adalimumab, tocilizumab within 8 weeks of screening or anakinra within 1 week of screening.
-Treatment with any investigational drug within 1 month of screening, or 5 half-lives, if known ( whichever is longer).
-Abnormal laboratory tests at screening: -Alanine transaminase (ALT) or aspartate transaminase (AST) >2 times upper limit of normal range (ULN); -Hemoglobin <11 g/100 mL for male and <10 g/100 mL for female;
-Neutrophils <1500/mm^3 (except <1000/mm3 for those of African descent); -Platelets <100 000/mm^3;
-Creatinine ≥150 μmol/L. Note: Laboratory parameters may be repeated once during the screening period if felt to be spurious or due to technical error in order to determine eligibility.
-Current history of substance and/or alcohol abuse -Current employee of Sanofi or has an immediate family member (eg, spouse, parents, child or sibling) who is a current employee of Sanofi. -Currently incarcerated or anticipated/scheduled to be incarcerated during the course of the study. -Any condition or circumstance that will preclude the patient from following and completing protocol requirements, in the opinion of the Investigator. -Pregnant or breastfeeding woman -Women who are of childbearing potential not protected by highly-effective contraceptive method(s) of birth control as (defined in the informed consent form and/or Appendix G for United Kingdom), and/or who are unwilling or unable to be tested for pregnancy. Note: Women of childbearing potential must have a confirmed negative pregnancy test at screening and randomization visits. They must use an effective contraceptive method throughout the entire duration of the study treatment, and for at least 12 weeks after the last administration of IMP

E.5 End points

E.5.1

Primary end point(s)

Change from baseline in mRSS

E.5.1.1

Timepoint(s) of evaluation of this end point

From baseline to Week 24

E.5.2

Secondary end point(s)

- Change from baseline in Health Assessment Questionnaire Disability Index (HAQ-DI), assessed with SHAQ
- Change from baseline in respiratory function as measured by observed Forced Vital Capacity (FVC)
Change from baseline in observed Carbon Monoxide Diffusing Lung Capacity (DLco [corrected for hemoglobin])

E.5.2.1

Timepoint(s) of evaluation of this end point

From baseline to Week 24

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

Yes

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

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

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

Yes

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

Argentina

Austria

Belgium

Estonia

France

Germany

Italy

Mexico

Poland

Romania

Russian Federation

Ukraine

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

Yes

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

LVLS

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

E.8.9.2

In all countries concerned by the trial months

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

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)

None

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

2016-08-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-09-26

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2019-04-01

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