Clinical Trials Register

Summary
EudraCT Number:	2007-006603-20
Sponsor's Protocol Code Number:	C1377T04
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2009-05-14
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2007-006603-20

A.3

Full title of the trial

A Phase 2, 2-Part, Multicenter, Randomized, Double-blind,
Parallel-group, Placebo-controlled, Proof-of-concept, dose-finding
Study Evaluating the Efficacy and Safety of CNTO 136
Administered Subcutaneously in Subjects with Active Rheumatoid
Arthritis Despite Methotrexate Therapy

A.3.2

Name or abbreviated title of the trial where available

Not available

A.4.1

Sponsor's protocol code number

C1377T04

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

Not available

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Centocor B.V.
B.1.3.4	Country	Netherlands
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
B.5.2	Functional name of contact point

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	CNTO136
D.3.2	Product code	CNTO136
D.3.4	Pharmaceutical form	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	not available
D.3.9.2	Current sponsor code	CNTO 136
D.3.9.3	Other descriptive name	CNTO 136 IgG
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	50
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	monoclonal antibody

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

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	LLT
E.1.2	Classification code	10039073
E.1.2	Term	Rheumatoid arthritis

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Part A: The objective of Part A is to evaluate efficacy and safety of CNTO 136
100 mg SC q2w in reducing signs and symptoms in subjects with active RA despite MTX. If efficacy
and safety are demonstrated in Part A, then the Interim Analysis Executive Committee will decide to
initiate Part B of the study.
Part B: The objectives of Part B are to determine efficacious and safe dose regimens of CNTO 136 SC
in reducing the signs and symptoms of active RA, describe the pharmacokinetic profile of CNTO 136
SC in subjects with RA, and assess the pharmacodynamic effects of CNTO 136 SC in subjects with RA
despite MTX.

E.2.2

Secondary objectives of the trial

not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Men or women 18 years of age or older.
2. Have a diagnosis of RA (according to the revised 1987 criteria of the ARA; Arnett et al, 1988) for at least 4 months prior to screening.
3. Are currently being treated with MTX at a dose of ≥15 mg/week for at least
4 months prior to screening and with an inadequate response to therapy according to the investigator. MTX doses of 10 or 12.5 mg/week are permitted only if 15 mg/week has not been tolerated. MTX route of administration and dose (not to exceed 25 mg/week) should be stable for at least 6 weeks prior to the first administration of the study agent, and the subjects should have no serious toxic side effects attributable to MTX.
4. Have active RA as defined, for the purpose of this study, by persistent disease activity with at least 6 swollen and 6 tender joints at the time of screening and at baseline and must be anti-CCP antibody-positive or RF positive at screening.
5. Screening CRP ≥ 1.0 mg/dL (SI: 10 mg/L)
6. If using oral corticosteroids, must be on a stable dose equivalent to ≤10 mg/day of prednisone for at least 2 weeks prior to the first administration of study agent. If currently not using corticosteroids, the subject must not have received oral corticosteroids for at least 2 weeks prior to the first administration of study agent.
7. If using NSAIDs or other analgesics for RA, must be on a stable dose for at least 2 weeks prior to the first administration of study agent.
8. If using sulfasalazine (SSZ), hydroxychloroquine (HCQ), or chloroquine (CQ), should have started treatment at least 3 months prior to the first administration of study agent and should have no serious toxic side effects attributable to the disease modifying antirheumatic drug (DMARD). If using SSZ, HCQ, or CQ, must also be on a stable dose for at least 4 weeks prior to the first administration of study agent.
If currently not using SSZ, HCQ, or CQ, must have not received these DMARDs
for at least 4 weeks prior to the first administration of the study agent.
9. Women of childbearing potential or men capable of fathering children must be using adequate birth control measures (eg, abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, surgical sterilization) during the study and for 6 months after receiving the last administration of study agent. Female subjects of childbearing potential must test negative for pregnancy.
10. Are willing and able to adhere to the study visit schedule and other protocol requirements.
11. Are capable of providing informed consent, which must be obtained prior to any study-related procedures.

E.4

Principal exclusion criteria

1. Have inflammatory diseases other than RA, including but not limited to psoriatic arthritis (PsA), ankylosing spondylitis (AS), systemic lupus erythematosus, or Lyme disease that might confound the evaluation of the benefit of CNTO 136 therapy in arthritis.
2. Have a marked baseline prolongation of the time between the beginning of the QRS complex and the end of the T-wave, adjusted for heart rate (normal 350-440 milliseconds) (QTc) interval, a history of risk factors for Torsade de Pointes such as persistent hypokalemia or family history of long QT syndrome; or a history of second or third-degree heart block.
3. Are infected with HIV, hepatitis B, or hepatitis C. (part B only)
4. Have current signs or symptoms of severe, progressive, or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or cerebral disease.
5. Have a history of, or ongoing chronic or recurrent infectious disease, including but not limited to, chronic renal infection, chronic chest infection (eg, bronchiectasis), sinusitis, recurrent urinary tract infection (eg, recurrent pyelonephritis, chronic nonremitting cystitis), an open, draining, or infected skin wound, or an ulcer.
6. Have had a serious infection (including but not limited to hepatitis, pneumonia, sepsis, or pyelonephritis), or have been hospitalized for an infection, or have been treated with IV antibiotics for an infection within 2 months prior to the first administration of study agent. Less serious infections (eg, acute upper respiratory tract infection, simple urinary tract infection) need not be considered exclusionary at the discretion of the investigator.
7. Have any known malignancy or have a history of malignancy within the previous 5 years (with the exception of a nonmelanoma skin cancer that has been treated with no evidence of recurrence for at least 3 months).
8. Have a history of active TB prior to screening; or have signs and symptoms suggestive of active TB; or have had recent close contact with a person with active TB.
9. Have a chest radiograph, both posterior-anterior and lateral views, taken within 3 months prior to the first administration of study agent that shows an abnormality suggestive of a malignancy or current active infection.
10. History or presence of any uncontrolled psychiatric or emotional disorder, (including drug and alcohol abuse with in the past 3 years), that might prevent the successful completion of the study.
11. Exclusionary labs include: a. Hemoglobin < 8.5 g/dL (SI: < 85 g/L) or < 5.3 mmol/L. b. WBC < 3.5 x 10^3 cells/μL (SI: < 3.5 x 10^9 cells/L). c. Neutrophils < 1.5 x 10^3 cells/μL (SI: < 1.5 x 10^9 cells/L). d. Platelets < 140 x 10^3 cells/μL (SI: < 140 x 10^9 cells/L). e. ALT and AST levels > 1.5 times the ULN for the central laboratory conducting the test. f. Serum creatinine ≥ 2.0 mg/dL (SI: 177 μmol/L).
12. Has a known allergy to any of the following: dextrose, sucrose, L-histidine, L-histidine monohydrochloride, Polysorbate 80.
13. Previous serious hypersensitivity reaction to monoclonal antibodies.
14. Have used biologic agent(s) targeted at reducing TNF.
15. Have received tocilizumab (anti-IL-6 receptor).
16. Have received cytotoxic drugs such as cyclophosphamide, chlorambucil, nitrogen
mustard, or other alkylating agents.
17. Have received a B-cell depleting biologic therapy (eg, rituximab) within 12 months of first study agent administration, or persistent evidence of B-cell depletion at the time of screening.
18. Have received leflunomide within 3 months prior to the first study agent administration and have not undergone a drug elimination procedure.
19. Have received abatacept (Orencia) within 3 months prior to the first study agent administration.
20. Have received any investigational agent within 3 months prior to the first study agent administration or within 5 half-lives of agent, which ever is longer.
21. Have received, or are expected to receive, any live virus or bacterial vaccination within 3 months before the first administration of study agent, during the study, or within 6 months after the last administration of study agent.
22. Have received systemic immunosuppressives or DMARDs other than MTX, SSZ, HCQ, or CQ, within 4 weeks prior to the first study agent administration. Medications in these categories include, but are not limited to azathioprine, oral cyclosporine A, tacrolimus, mycophenolate mofetil, D-penicillamine, oral or parenteral gold, IL-1ra [anakinra], and leflunomide.
23. Have received intra-articular, IM, or IV corticosteroids, including adrenocorticotrophic hormone during the 4 weeks prior to first study agent administration.
24. Receiving any other concomitant medication not specifically listed that in the opinion of the investigator might adversely affect the study outcome.

E.5 End points

E.5.1

Primary end point(s)

ACR 50 response at Week 12 in Part B.

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

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

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

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.8.3

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

Information not present in EudraCT

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

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

last visit last 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	No
F.1.1.1	In Utero	Information not present in EudraCT
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	Information not present in EudraCT
F.1.1.3	Newborns (0-27 days)	Information not present in EudraCT
F.1.1.4	Infants and toddlers (28 days-23 months)	Information not present in EudraCT
F.1.1.5	Children (2-11years)	Information not present in EudraCT
F.1.1.6	Adolescents (12-17 years)	Information not present in EudraCT
F.1.2	Adults (18-64 years)	Yes
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	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
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	40
F.4.2	For a multinational trial
F.4.2.1	In the EEA	75
F.4.2.2	In the whole clinical trial	190

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

2009-07-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2009-06-03

P. End of Trial
P.	End of Trial Status	Completed

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials