Clinical Trials Register

Summary
EudraCT Number:	2011-001460-22
Sponsor's Protocol Code Number:	WA27788
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-10-20
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

Germany - PEI

A.2

EudraCT number

2011-001460-22

A.3

Full title of the trial

A Phase II/III, Multicenter, Randomized, Double Blind, Placebo-Controlled Study To Assess The Efficacy And Safety Of Tocilizumab Versus Placebo In Patients With Systemic Sclerosis

A.3.1

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

A clinical study conducted at many clinical sites. In this study patients will be randomly assigned to one of two treatments. Neither staff at the site nor the patient nor the sponsor’s team will know if the patient received drug with an active ingredient or drug without an active ingredient. The goal is to see if the drug improves the progression of the disease in patients with systemic sclerosis and what the side effects are.

A.3.2

Name or abbreviated title of the trial where available

N/A

A.4.1

Sponsor's protocol code number

WA27788

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	F. Hoffmann-La Roche Ltd.
B.1.3.4	Country	Switzerland
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	F. Hoffmann-La Roche Ltd.
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	F. Hoffmann-La Roche Ltd.
B.5.2	Functional name of contact point	Trial Information Support Line-TISL
B.5.3	Address:
B.5.3.1	Street Address	Grenzacherstrasse 124
B.5.3.2	Town/ city	Basel
B.5.3.3	Post code	4070
B.5.3.4	Country	Switzerland
B.5.6	E-mail	global.rochegenentechtrials@roche.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	Yes
D.2.1.1.1	Trade name	RoActemra
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration Limited
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	tocilizumab SC 162 mg/0.9 ml prefilled syringe with safety device (PFS)
D.3.2	Product code	Ro 487-7533/F10-04
D.3.4	Pharmaceutical form	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.3.8	INN - Proposed INN	tocilizumab
D.3.9.1	CAS number	375823-41-9
D.3.9.2	Current sponsor code	RO4877533
D.3.9.3	Other descriptive name	Recombinant humanized anti-human monoclonal antibody directed against the IL-6R
D.3.9.4	EV Substance Code	SUB20313
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	180
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	Yes
D.3.11.13.1	Other medicinal product type	Recombinant humanized anti-human monoclonal antibody directed against the IL-6R

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
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 (SSc)

E.1.1.1

Medical condition in easily understood language

This disease is characterized by scaring of the skin and internal organs. This leads to tightening and thickening of the skin and can lead to problems with other internal organ functions.

E.1.1.2

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.1
E.1.2	Level	PT
E.1.2	Classification code	10042953
E.1.2	Term	Systemic sclerosis
E.1.2	System Organ Class	10028395 - Musculoskeletal and connective tissue disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

•To assess the efficacy of treatment with TCZ 162 mg SC versus placebo SC given every week to patients with SSc, at Week 24 using the mRSS
•To assess the safety of treatment with TCZ 162 mg SC versus placebo SC given every week

E.2.2

Secondary objectives of the trial

•To assess the efficacy of TCZ 162 mg SC versus placebo on improvement of physical function (as measured by the Scleroma Health Assessment Questionaire-Disability Index [SHAQ-DI])
•To assess the efficacy of TCZ 162 mg SC versus placebo on patient’s global assessment
•To assess the efficacy of TCZ 162 mg SC versus placebo on improvement of the clinician's global assessment
•To assess the efficacy of TCZ 162 mg SC versus placebo on fatigue (as measured by Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-Fatigue] score)
•To assess the efficacy of TCZ 162 mg SC versus placebo as measured on Pruritus 5-D Itch Scale (5-D Itch Scale)
•To assess the efficacy of TCZ 162 mg SC versus placebo at Week 48 on skin thickness using the mRSS
•To assess the proportion of patients with maintenance of mRSS response from Week 24 to Week 48
•To characterize the PK and PD profile of TCZ 162 mg SC
•To assess the immunogenicity of TCZ 162 mg SC

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

To determine the pharmacokinetics of TCZ in SSc patients, additional PK samples following the first SC dose at baseline and the Week 16 dose will be drawn from approximately 24 patients at selected sites.

E.3

Principal inclusion criteria

•Ability and willingness to give written informed consent and comply with the requirements of the study protocol
•Diagnosis of SSc, as defined using ACR criteria
•Disease duration of ≤ 60 months (defined as time from the first non-Raynaud phenomenon manifestation)
•Age ≥ 18 years
•≥ 15 and ≤ 40 mRSS units at the screening visit
•Uninvolved skin at injection sites
•Active disease

E.4

Principal exclusion criteria

•Rheumatic autoimmune disease other than SSc, including but not limited to, RA, systemic lupus erythematosis, mixed connective tissue disorder, polymyositis, dermatomyositis, eosinophilic fasciitis, primary Sjögren syndrome and eosinophilic myalgia syndrome
•Skin thickening (scleroderma) limited to areas distal to the elbows or knees at screening
•History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies
•Evidence of moderately severe concomitant nervous system, renal, endocrine or GI disease, as determined by the Principal Investigator
•Pulmonary disease with FVC ≤ 50% of predicted or a DLCO (hemoglobin corrected) ≤ 40% of predicted

E.5 End points

E.5.1

Primary end point(s)

modified Rodnan Skin Score

E.5.1.1

Timepoint(s) of evaluation of this end point

week 24

E.5.2

Secondary end point(s)

•Change in HAQ-DI score from baseline at week 24 and week 48
•Change in patient’s global assessment from baseline at week 24 and week 48
•Change in clinician’s global assessment from baseline at week 24 and week 48
•Change in FACIT-F score from baseline at week 24 and week 48
•Change in Pruritus 5-D Itch scale from baseline at week 24 and week 48
•Change in mRSS from baseline at week 48
•Proportion of patients with mRSS at week 48 ≥ mRSS at week 24
•Change in VAS scores from baseline (intestinal, breathing, Raynaud’s, finger ulcers, overall disease VAS scores from SHAQ-DI) at Weeks 24 and 48

E.5.2.1

Timepoint(s) of evaluation of this end point

week 24 and/or week 48

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

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

Yes

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Immunogenicity assessment

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

Yes

E.7.1.3.1

Other trial type description

Phase II/III

E.7.2

Therapeutic exploratory (Phase II)

Yes

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

Yes

E.8.1.7.1

Other trial design description

48-week blinded period followed by a 48-week open-label period

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

Canada

France

Germany

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

The end of the study will occur when the last participating patient completes the last scheduled visit or when the Sponsor decides to discontinue the study or development program.

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

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)

After completion of the study, patients will be transitioned to standard of care at the investigator's discretion. No post-study provisional care will be provided.

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

2011-11-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-11-28

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2015-06-16

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