Clinical Trials Register

Summary
EudraCT Number:	2010-020839-39
Sponsor's Protocol Code Number:	RA0056Amend4
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2010-10-12
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

2010-020839-39

A.3

Full title of the trial

A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, DOSE RANGING STUDY WITH
AN ACTIVE COMPARATOR TO EVALUATE THE EFFICACY AND SAFETY OF CDP6038 ADMINISTERED SUBCUTANEOUSLY FOR 12 WEEKS TO SUBJECTS WITH ACTIVE RHEUMATOID ARTHRITIS HAVING PREVIOUSLY FAILED TNF-BLOCKER THERAPY

A.3.1

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

Efficacy and safety of CDP6038 in patients with rheumatoid arthritis with an unsuccessful response to anti-TNF therapy

A.3.2

Name or abbreviated title of the trial where available

RA0056

A.4.1

Sponsor's protocol code number

RA0056Amend4

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	UCB Biosciences, Inc
B.1.3.4	Country	United States
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	TBC
B.5.2	Functional name of contact point
B.5.6	E-mail	clinicaltrials@ucb.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	Olikizumab
D.3.2	Product code	CDP6038
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	Olokizumab
D.3.9.1	CAS number	1007223-17-7
D.3.9.2	Current sponsor code	CDP6038
D.3.9.3	Other descriptive name	Recombinant human Mab of IgG4 subtype
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	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.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	RoActemra 20 mg/ml concentrate for solution for infusion.
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
D.3.4	Pharmaceutical form	Concentrate for solution for 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	RoActemra®
D.3.9.1	CAS number	375823-41-9
D.3.9.2	Current sponsor code	EU/1/08/492/001-6
D.3.9.3	Other descriptive name	TOCILIZUMAB
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	20
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	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

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	14.1
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

The primary objective of this study is to evaluate the efficacy of CDP6038 administered sc at various doses and dose administration frequencies relative to placebo.

E.2.2

Secondary objectives of the trial

The secondary objectives of this study are:
• To evaluate the safety of CDP6038 at various doses and dose administration frequencies relative to placebo
• To assess the PK and immunogenicity of repeated doses of CDP6038
• To assess the dose- and exposure-response relationships of CDP6038 with efficacy

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

To be eligible to participate in this study, all of the following criteria must be met:
1. Subject must be able to understand the information provided to them, be given ample time and opportunity to ask questions and to decide whether or not to participate, and provide written informed consent. The subject should also be able to communicate satisfactorily with the Investigator and be willing to participate in the study and to comply with all study requirements.
2. Subject must be at least 18 years old at Screening and weigh ≥40kg.
3. Subject must have a diagnosis of adult-onset RA of at least 6 months’ (24 weeks)
duration as defined by the 1987 ACR classification criteria (Arnett et al, 1988) or a score of ≥6 as defined by the ACR/European League Against Rheumatism Classification and Diagnostic Criteria for RA (Aletaha et al, 2010).
4. Subject must have moderately to severely active RA disease as defined by each of the following:
◦ ≥6 tender joints (68-joint count) at Screening and Baseline
◦ ≥6 swollen joints (66-joint count) at Screening and Baseline
◦ CRP ≥1.2 times the upper limit of normal (ULN) (central laboratory) or ESR
>28mm/hour (Westergren)
5. Subject must be on a dose of MTX between 15 to 25mg/week, which has been stable for at least 6 weeks prior to Screening with a stable route of administration. Subjects may be dosed with 10 to less than 15mg weekly if they have documented reasons of toxicity. Subjects must be willing to initiate, or continue on, folate supplementation while taking MTX during the study (see Section 7.8.1).
6. Subject must have had intolerance or inadequate response to treatment (ie, TNF-blocker failure) with no more than 2 licensed TNF-blocker therapies (etanercept, infliximab, golimumab, certolizumab pegol, or adalimumab) prior to study entry.
7. Female subjects must be either postmenopausal for at least 1 year, surgically incapable of childbearing, or effectively practicing an acceptable method of contraception (either oral/parenteral/implantable hormonal contraceptives, intrauterine device, or barrier and spermicide). Abstinence is not considered an acceptable method of contraception for this study. Female subjects of childbearing potential must agree to use adequate contraception during the study and for 6 months (24 weeks) after their last CDP6038 dose. Male subjects must agree to ensure that they or their female partner(s) use adequate contraception during the study and for 12 weeks after the subject receives their last dose of CDP6038.

E.4

Principal exclusion criteria

Rheumatoid arthritis disease-related and other treatment-related exclusions:
1. Subjects who have a diagnosis of any other inflammatory arthritis (eg, psoriatic arthritis, ankylosing spondylitis, or gout, or lupus or Sjögren’s syndrome (primary or secondary).
2. Subjects who have a secondary, noninflammatory type of arthritis (eg, osteoarthritis or fibromyalgia) that in the Investigator’s opinion is symptomatic enough to interfere with evaluation of the effect of IMP on the subject’s primary diagnosis of RA.
3. Subject who is Steinbrocker IV functional capacity.
4. Subjects must be free of the prohibited medications (as detailed in section 6.2 of the study protocol)
5. Subjects must be free of biological therapy (as detailed in section 6.2 of the study protocol)
6. Participation in any other clinical drug or device study (including a biologic product)
within 12 weeks or 5 half-lives, or within protocol-specified durations for specific agents, whichever is longer, prior to Baseline.
Medical history-related exclusions:
7. Subject has a creatinine level, an alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level, platelets or a white blood cell count, or a neutrophil count at Screening in accordance with the protocol parameters (refer to protocol).
8. Female subjects who are breast-feeding, pregnant, or plan to become pregnant during the study or within 24 weeks following last dose of IMP.
9. Subjects who have a history of an infected joint prosthesis at any time with that prosthesis still in situ.
10. Subject with a history of chronic or recurrent infections (refer to protocol).
11. Subjects with known history of or current clinically active infection with Histoplasma, Coccidiodes, Paracoccidioides, Pneumocystis, nontuberculous mycobacteria, Blastomyces, or Aspergillus.
12. Subjects at high risk of infection (eg, presence of leg ulcers or an indwelling urinary catheter, bedridden, or wheelchair-bound subjects).
13. Subjects with known concurrent acute or chronic viral hepatitis B or C infection.
14. Subjects with known human immunodeficiency virus (HIV) infection.
15. Subject has: a) known TB disease, b) high risk of acquiring TB infection, c) a positive or indeterminate TB test result, or d) radiographic evidence of TB (refer to protocol).
16. Subjects that have received vaccinations within 8 weeks prior to Screening or plan to receive vaccines during the study (with the exception of injectable influenza and pneumococcal vaccinations which are permitted).
17. Concurrent malignancy or a history of malignancy (refer to protocol).
18. Subjects with a history of a lymphoproliferative disorder, including lymphoma or signs and symptoms suggestive of lymphoproliferative disease.
19. Subjects with a history or presence of cardiovascular, respiratory, hepatic, renal,
gastrointestinal, endocrinological, dermatological, neurological, psychiatric,
hematological (including bleeding disorder), or immunologic/immunodeficiency
disorder(s) which are clinically significant enough in the opinion of the Investigator or
Sponsor to alter the absorption and disposition of IMP, or constitute a possible
confounding factor for assessment of efficacy or safety of the IMP.
20. Subjects with a current or recent history of severe, progressive, and/or uncontrolled renal,
hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac (including but not
limited to familial hypertriglyceridemia and Class III or IV congestive heart failure according to the New York Heart Association 1994 classification criteria [The Criteria Committee of the New York Heart Association, 1994]), neurological (including cerebral disease) disease.
21. Subjects with planned surgery during the study or surgery ≤1 week prior to Screening.
22. Subject with a history of chronic alcohol abuse within the last 1 year.
23. Subject with a history of drug addiction within the last 1 year or current drug addiction or use of illicit drugs.
24. Subject has a known hypersensitivity to any components of the IMP or comparative drugs as stated in this protocol.
25. Subject is legally institutionalized.
26. Employees of the Investigator or study center, with direct involvement in the proposed study or other studies under the direction of that Investigator or study center, as well as family members of the employees or the Investigator.
27. Subjects with any other condition (eg, clinically significant laboratory values besides those prespecified in Exclusion Criterion 7) which in the Investigator’s or Sponsor’s judgment would make the subject unsuitable for inclusion in the study.

E.5 End points

E.5.1

Primary end point(s)

Efficacy variables
The primary efficacy variable is the change from Baseline in the DAS28(CRP) for CDP6038 and placebo.

Primary pharmacokinetic/pharmacodynamic variables
Dose leading to 50% of the maximum effect (D50) on DAS28(CRP)
• Exposure leading to 50% of the maximum effect on DAS28(CRP)
• Concentration leading to 50% of the maximum effect (EC50) on DAS28(CRP)
• Slope of effect (γ) on DAS28(CRP)

E.5.1.1

Timepoint(s) of evaluation of this end point

Efficacy variables
The primary efficacy variable is the change from Baseline in the DAS28(CRP) at Week 12 for CDP6038 and placebo.

E.5.2

Secondary end point(s)

The secondary efficacy variables are the ACR20, ACR50, and ACR70 response rates at for CDP6038 and placebo.

E.5.2.1

Timepoint(s) of evaluation of this end point

The secondary efficacy variables are the ACR20, ACR50, and ACR70 response rates at Week 12 for CDP6038 and placebo.

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

Yes

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

Yes

E.8.1.7.1

Other trial design description

Double-blind, placebo and active-controlled, factorial design, randomized study

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

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

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 is defined in the protocol in section "5.1.1 Study duration per subject".

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:

220

F.1.3

Elderly (>=65 years)

Yes

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

220

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)

Subjects who complete the study will be eligible to receive CDP6038 in the open-label extension study, RA0057, until the approval of the marketing application for the indication of RA in the subject’s country or region or until further notice from UCB. A follow up on all adverse events as described in the protocol section 12, Assessment of Safety, will also be performed.

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

2010-12-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-02-25

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2012-06-29

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