Clinical Trials Register

Summary
EudraCT Number:	2014-002541-22
Sponsor's Protocol Code Number:	EFC14092
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2015-01-09
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

UK - MHRA

A.2

EudraCT number

2014-002541-22

A.3

Full title of the trial

A randomized, double-blind, parallel-group study assessing the efficacy and safety of sarilumab monotherapy versus adalimumab monotherapy in patients with rheumatoid arthritis

A.3.1

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

Efficacy and safety of Sarilumab and Adalimumab monotherapy in patients with Rheumatoid Arthritis

A.3.2

Name or abbreviated title of the trial where available

SARIL-RA-MONARCH

A.4.1

Sponsor's protocol code number

EFC14092

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 Recherche & Développement
B.5.2	Functional name of contact point	Medical Information
B.5.3	Address:
B.5.3.1	Street Address	One Onslow Street
B.5.3.2	Town/ city	Guildford
B.5.3.3	Post code	GU1 4YS
B.5.3.4	Country	United Kingdom
B.5.6	E-mail	uk-medicalinformation@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.3.1	Product name	Sarilumab
D.3.2	Product code	SAR153191 (REGN88)
D.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
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.3.8	INN - Proposed INN	Sarilumab
D.3.9.2	Current sponsor code	SAR153191
D.3.9.4	EV Substance Code	SUB30938
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	200
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	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Yes
D.2.1.1.1	Trade name	Humira, 40 mg solution for injection in pre-filled syringe
D.2.1.1.2	Name of the Marketing Authorisation holder	AbbVie Ltd
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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.3.1	Product name	adalimumab
D.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
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.3.8	INN - Proposed INN	ADALIMUMAB
D.3.9.1	CAS number	331731-18-1
D.3.9.4	EV Substance Code	SUB20016
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	40
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	No
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	Solution for injection in pre-filled syringe
D.8.4	Route of administration of the placebo	Subcutaneous use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection in pre-filled syringe
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

Rheumatoid Arthritis

E.1.1.1

Medical condition in easily understood language

Rheumatoid Arthritis

E.1.1.2

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.1
E.1.2	Level	PT
E.1.2	Classification code	10039073
E.1.2	Term	Rheumatoid arthritis
E.1.2	System Organ Class	10028395 - Musculoskeletal and connective tissue disorders

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 demonstrate that sarilumab monotherapy is superior to adalimumab monotherapy with respect to signs and symptoms as assessed by disease activity score 28 (DAS28)-erythrocyte sedimentation rate (ESR) in patients with active rheumatoid arthritis (RA) who are either intolerant of, or considered inappropriate candidates for continued treatment with methotrexate (MTX), or after at least 12 weeks of continuous treatment with MTX, are determined to be inadequate responders.

E.2.2

Secondary objectives of the trial

To demonstrate that sarilumab monotherapy is superior to adalimumab monotherapy in patients with active RA who are either intolerant of, or considered inappropriate candidates for continued treatment with methotrexate (MTX), or after at least 12 weeks of continuous treatment with MTX, are determined to be inadequate responders, with respect to:
• Reduction of signs and symptoms of RA
• Improvement in quality of life assessed by patient reported outcome questionnaires.
Assessment of the safety and tolerability of sarilumab monotherapy (including immunogenicity) throughout the study.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Diagnosis of rheumatoid arthritis ≥3 months duration.
American College of Rheumatology (ACR) Class I-III functional status.
Active RA, defined as:
- At least 6 of 66 swollen joints and 8 of 68 tender joints,
- High sensitivity C-reactive protein (hs-CRP)≥8 mg/L or ESR≥28 mm/H, and
- DAS28ESR >5.1.
Patients who per investigator judgment were either intolerant of, or considered
inappropriate candidates for continued treatment with methotrexate (MTX), or after at least 12 weeks of continuous treatment with MTX, or inadequate responders treated with an adequate MTX dose for at least 12 weeks.

E.4

Principal exclusion criteria

Age <18 years or the legal age of consent in the country of the study site, whichever is higher.
Current treatment with disease-modifying antirheumatic drug (DMARDs)/immunosuppressive agents including MTX, cyclosporine, mycophenolate, tacrolimus, gold, penicillamine, sulfasalazine or hydroxychloroquine within 2 weeks prior to the baseline (Randomization Visit) or azathioprine, cyclophosphamide within 12 weeks prior to baseline (Randomization Visit) or leflunomide within 8 weeks prior to the Randomization Visit, or 4 weeks after cholestyramine washout.
Treatment with any prior biologic agent, including anti-interleukin 6 (IL-6), IL-6 receptor (IL-6R) antagonists, and prior treatment with a Janus kinase inhibitor.
Use of parenteral corticosteroids or intra-articular corticosteroids within 4 weeks prior to screening.

E.5 End points

E.5.1

Primary end point(s)

Change from baseline in disease activity score 28 (DAS28) - erythrocyte sedimentation rate (ESR)

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 24

E.5.2

Secondary end point(s)

1- American College of Rheumatology 20 (ACR2020, ACR50 and ACR70 response
2- Change from baseline in each individual ACR component
3- Change from baseline in DAS28-CRP
4- DAS28-ESR remission (<2.6)
5- DAS28-CRP remission (<2.6)
6- Low disease activity (DAS28-ESR <3.2)
7- Remission based on clinical disease activity index (CDAI) (≤2.8)
8- Change from baseline in CDAI
9- Sarilumab exposure assessed by trough serum sarilumab concentrations.
10- Change from baseline in: short form 36 (SF-36) scores
Change from baseline in: EQ-5D-3L scores
Change from baseline in: rheumatoid arthritis impact of disease (RAID) scores
Change from baseline in: work productivity survey-rheumatoid arthritis (WPS-RA) scores
Change from baseline in: functional assessment of chronic illness therapy-fatigue (FACIT-F) scores
Change from baseline in: morning stiffness visual analog scale (VAS) scores
11- Number of patients with adverse events
Clinically significant changes in laboratory values, ECG and vital signs
Measurement of anti-drug antibody (ADA) levels

E.5.2.1

Timepoint(s) of evaluation of this end point

1 to 8: week 24
9: week 54
10: week 24
11: week 54

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

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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)

Yes

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

Argentina

Chile

Czech Republic

Germany

Hungary

Israel

Korea, Republic of

Mexico

Peru

Poland

Puerto Rico

Romania

Russian Federation

South Africa

Spain

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

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects
F.1 Age Range
F.1.1	Trial has subjects under 18	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.2.1	Number of subjects for this age range:	230
F.1.3	Elderly (>=65 years)	Yes
F.1.3.1	Number of subjects for this age range:	110
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	No
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	5
F.4.2	For a multinational trial
F.4.2.1	In the EEA	182
F.4.2.2	In the whole clinical trial	340

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

2015-03-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-03-18

P. End of Trial
P.	End of Trial Status	GB - no longer in EU/EEA

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