Clinical Trials Register

Summary
EudraCT Number:	2010-022382-10
Sponsor's Protocol Code Number:	CCX114151
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2010-10-22
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 - BfArM

A.2

EudraCT number

2010-022382-10

A.3

Full title of the trial

A Randomised, Double-blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of GSK1605786A in the Treatment of Subjects with Moderately-to Severely Active Crohn’s Disease

A.3.1

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

A Randomised, Double-blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of GSK1605786A in the Treatment of Subjects with Moderately-to-Severely Active Crohn’s Disease.

A.4.1

Sponsor's protocol code number

CCX114151

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	GlaxoSmithKline Research & Development Ltd
B.1.3.4	Country	United Kingdom
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	GSK R & D Ltd
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	GlaxoSmithKline Research & Development Ltd
B.5.2	Functional name of contact point	Clincial Trials HelpDesk
B.5.3	Address:
B.5.3.1	Street Address	Iron Bridge Road
B.5.3.2	Town/ city	Uxbridge
B.5.3.3	Post code	UB11 1BU
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+44208990 44 66
B.5.5	Fax number	+44208990 12 34
B.5.6	E-mail	GSKClincialSupportHD@gsk.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	GSK1605786A
D.3.2	Product code	GSK1605786A
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	GSK1605786A
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	250
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	Capsule, hard
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Subjects with Moderately-to-Severely Active Crohn’s Disease

E.1.1.1

Medical condition in easily understood language

Crohn’s disease Inflammatory bowel disease

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	15.0
E.1.2	Level	PT
E.1.2	Classification code	10011401
E.1.2	Term	Crohn's disease
E.1.2	System Organ Class	10017947 - Gastrointestinal 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 assess the efficacy of GSK1605786A compared with placebo as an induction
therapy in subjects with moderately-to-severely active Crohn’s disease over 12
weeks.

E.2.2

Secondary objectives of the trial

• To evaluate the safety of GSK1605786A compared with placebo
• To investigate the effect of GSK1605786A compared with placebo on health related quality of life
• To investigate the effect of GSK1605786A compared with placebo on healthcare related resource utilisation
• To investigate the effect of GSK1605786A compared with placebo on work productivity and activity impairment
• To investigate the effect of GSK1605786A compared with placebo on biomarkers of inflammation [C-reactive protein (CRP) and faecal calprotectin]
• To explore the dose relationships between GSK1605786A plasma concentration and clinical response endpoints
• To explore potential relationships between genetic variants and GSK1605786A efficacy and safety endpoints.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female subjects aged ≥18 years
2. Written informed consent prior to any of the screening procedures including
discontinuation of prohibited medications
3. A diagnosis of Crohn’s disease for > 4 months duration with small bowel and/or
colonic involvement
4. Confirmation of Crohn’s disease established by visualisation of the gastrointestinal
tract within the 12 months prior to screening or by screening endoscopy at study
entry. Acceptable methods for gastrointestinal tract visualisation include, but are not
limited to endoscopy, capsule endoscopy, MRI or barium X-ray. Subjects without
visualisation of the gastrointestinal tract within 12 months of screening must be
willing to undergo endoscopy within the screening period
5. History of inadequate response and/or intolerance/adverse event leading to
discontinuation of at least one of the following treatments for Crohn’s disease:
corticosteroids, immunosuppressants
6. Current evidence of moderately-to-severely active disease characterised by a CDAI
score of ≥220 to ≤450 at Baseline (Week 0) [Criterion for Randomisation]
7. Confirmation of current active Crohn’s disease by either of the following [Criterion for Randomisation]:
a. Luminal ulceration visualised by Screening endoscopy and as adjudicated by central endoscopy reader, or
b. Elevated CRP (≥ 3 mg/L, the upper limit of normal (ULN) for the highly sensitive CRP test) plus elevated faecal calprotectin (> 200 μg/g stool) at Screening
8. Stable doses of permitted concomitant medications or having previously received, but are not currently receiving, medications for Crohn’s disease. Please refer to Section 5.5.1 Permitted Medications and Non Drug Therapies.
9. Demonstrated ability to comply with Crohn’s disease symptom recording using the IVRS; to be eligible for randomisation subject must complete recording of symptoms for at least 8 consecutive days prior to the randomisation/baseline visit (Week 0).
10. Females of child-bearing potential (FCBP) must be sexually inactive or commit to use of contraceptive methods with a failure rate of < 1% per year when used consistently and correctly and, when applicable, in accordance with the product label, for the duration of this study as defined by the following:
Contraceptive Methods with a Failure Rate of < 1%
• Abstinence from penile-vaginal intercourse, when this is the female’s preferred and usual lifestyle
• Oral contraceptive, either combined or progestogen alone
• Injectable progestogen
• Implants of etonogestrel or levonorgestrel
• Estrogenic vaginal ring
• Percutaneous contraceptive patches
• Intrauterine device (IUD) or intrauterine system (IUS) that meets the <1% failure rate as stated in the product label
• Male partner sterilization prior to the female subject's entry into the study, and this male is the sole partner for that subject. The information on the male sterility can come from the site personnel’s: review of subject’s medical records; medical examination of the subject and/or semen analysis; or interview with the subject on his medical history.
• Male condom combined with a vaginal spermicide (foam, gel, film, cream, or suppository)
• Male condom combined with a female diaphragm, either with or without a vaginal spermicide (foam, gel, film, cream, or suppository)
These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The Investigator is responsible for ensuring subjects understand how to properly use these methods of contraception. This list does not apply to FCBP with same sex partners, when this is their preferred and usual lifestyle.
Female subjects should not be enrolled if they are pregnant or lactating or if they plan to become pregnant during the time of study participation. A serum pregnancy test is required of all FCBP at Screening. In addition, a urine pregnancy test will be performed
at the Randomisation visit (Week 0) and at Weeks 4, 8, 12 and at the Early Withdrawal or Follow-up visits if applicable.
Country specific inclusion criterion for subjects in France: A subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

E.4

Principal exclusion criteria

1. If female, is pregnant, has a positive pregnancy test or is breast-feeding
2. Known coeliac disease, those who follow a gluten-free diet to manage symptoms of suspected coeliac disease and subjects with a positive screening test for coeliac disease (elevated anti- tissue transglutaminase antibodies)
3. Diagnosis of ulcerative or indeterminate colitis
4. Enterocutaneous, abdominal or pelvic fistulae with abscesses or fistulae likely to require surgery during the study period
5. Bowel surgery, other than appendectomy, within 12 weeks prior to screen and/or has surgery planned or deemed likely for CD during the study period
6. Extensive colonic resection, subtotal or total colectomy
7. Presence of ileostomies, colostomies or rectal pouches
8. Fixed symptomatic stenoses of small bowel or colon
9. History of more than 3 small bowel resections or diagnosis of short bowel syndrome
10. Chronic use of narcotics for chronic pain defined as daily use of one or more doses of narcotic containing medication
11. Use of prohibited medications, including enteral feeding or elemental diet, within their specified timeframes and throughout the study (Section 5.5.2 Prohibited Medications and Non Drug Therapies). Biologic use: Use of any TNF inhibitor (eg. infliximab, adalimumab or certolizumab) or natalizumab within 10 weeks prior to randomisation Corticosteroid use: Use of parenteral glucocorticoids within 4 weeks prior to screening Immunospressant use: Use of cyclosporine, tacrolimus, sirolimus or mycophenolate mofetil within 4 weeks prior to screening. For further information please view protocol pages 31-32
12. Positive immunoassay for C. difficile [Subjects who test positive and receive antibiotic treatment may be re-screened after 4 months if the re-test is negative]
13. Known HIV infection
14. Known varicella, herpes zoster, or other severe viral infection within 6 weeks of screening
15. Subjects who have received immunisation with a live vaccine e.g. measles, mumps, rubella (each as in MMR vaccine), oral polio, varicella, yellow fever, within 4 weeks of screening and throughout the study, with the exception of influenza vaccine
16. Active or latent tuberculosis (TB) infection: All subjects will be tested with QuantiFERON TB Gold test and those with a positive test result will be excluded. Please view protocol page 31 for further information.
17. Current sepsis or infections requiring intravenous antibiotic therapy >2 weeks
18. Previous infections characterised by opportunistic pathogens, and/or dissemination suggestive of clinically significant immunocompromise
19. The subject has congenital or acquired immunodeficiency or has evidence of immunocompromise manifested by current opportunistic infection
20. The subject exhibits evidence of hepatic dysfunction, viral hepatitis, or exhibits
serum ALT (SGPT) and/or AST (SGOT) values ≥2 times the upper limit of normal; has a total bilirubin value >1.5 times the upper limit of normal (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%); has alkaline phosphatase >1.5 times the upper limit of normal; has current or chronic history of liver disease including non-alcoholic steatohepatitis (NASH). Please view protocol page 32 for further information.
21. A positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) test or positive Hepatitis C test result at screening*
22. QTc ≥450 msec (≥480 msec for those with Bundle Branch Block)
a. either QTcb or QTcf, machine or manual overread, males or females. The QT correction formula used to determine exclusion and discontinuation should be the same throughout the study
b. based on single or average QTc value of an ECG obtained over a brief recording period
23. The subject has a concurrent illness or disability that may affect the interpretation of clinical data, or otherwise contraindicates participation in this clinical study (e.g., an unstable cardiovascular, autoimmune, renal, hepatic, pulmonary, endocrine, metabolic, gastrointestinal, haematologic, or neurological condition or mental impairment)
24. History or evidence of adenomatous colonic polyps that have not been removed
25. History of evidence of colonic mucosal dysplasia
26. The subject has current evidence of, or has been treated for, a malignancy within the past five years (other than localised basal cell, squamous cell skin cancer, cervical dysplasia, or any cancer in situ that has been resected)
27. Any previous participation in a clinical study of GSK1605786A (formerly ChemoCentryx compound CCX282-B)
28. Medical history of sensitivity to any of the components of GSK1605786A (microcrystalline cellulose, crospovidone, sodium stearyl fumarate)
29. Use of any investigational product within 30 days prior to screening.

E.5 End points

E.5.1

Primary end point(s)

• Proportion of subjects achieving clinical response, defined by CDAI decrease from baseline of ≥100 points, at Week 12

Safety Endpoints:
• Incidence of adverse events/serious adverse events
• Change from baseline in vital signs: heart rate and blood pressure
• Change from baseline in haematology and clinical chemistry parameters
• Change from baseline in liver function test parameters
• Change from baseline in 12 lead ECG abnormalities.

E.5.1.1

Timepoint(s) of evaluation of this end point

Safety assessments at Week 0, 4, 8, 12 and post 4 week follow-up at Week 16, if subject does not enrol in follow on study. 12 lead ECG at Screening and Week 12. CDAI assessments at Week 0, 4, 8, 12, and post 4 week follow-up at Week 16, if subject does not enrol in follow on study.

E.5.2

Secondary end point(s)

Key Secondary Efficacy Endpoint:
• Proportion of subjects in clinical remission, defined as a CDAI score of <150 points, at Week 12

E.5.2.1

Timepoint(s) of evaluation of this end point

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

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

Yes

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)

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)

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

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

Australia

Belgium

Canada

Czech Republic

Denmark

France

Germany

Japan

Netherlands

Norway

Sweden

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

Last Subject Last Visit

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