Clinical Trials Register

Summary
EudraCT Number:	2011-002818-37
Sponsor's Protocol Code Number:	CCX115393
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-10-03
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

Belgium - FPS Health-DGM

A.2

EudraCT number

2011-002818-37

A.3

Full title of the trial

A phase II, 20-week, multi-centre, randomised, double-blind, placebo-controlled, parallel group proof of concept study to investigate the efficacy and safety of GSK1605786 for treatment of patients with active Ulcerative Colitis.

A.3.1

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

A Phase II study to investigate GSK1605786 fo the treatment of patients with Ulcerative Colitis.

A.4.1

Sponsor's protocol code number

CCX115393

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	Clinical 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	+442089904466
B.5.5	Fax number	+442089901234
B.5.6	E-mail	GSKClinicialSupportHD@gsk.com
B.Sponsor: 2
B.1.1	Name of Sponsor
B.1.3.4	Country
B.3.1 and B.3.2	Status of the sponsor
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	GSK1605786A
D.3.2	Product code	GSK1605786A
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
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 Active Ulcerative Colitis.

E.1.1.1

Medical condition in easily understood language

Ulcerative Colitis

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	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10045365
E.1.2	Term	Ulcerative colitis
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 investigate the efficacy of GSK1605786 at week 12 following twice daily administration at 500 mg in patients with active Ulcerative Colitis (UC).

E.2.2

Secondary objectives of the trial

-To explore safety, tolerability and the time course of the efficacy of GSK1605786 following repeat dosing continued for up to 16 weeks.
-To assess the anti-inflammatory activity of GSK1605786 on blood and faecal biomarkers of intestinal inflammation.
-To investigate the systemic pharmacokinetics of GSK1605786 following twice daily administration at 500 mg.
-To measure CCR9 occupancy (RO) in peripheral blood following twice daily administration at 500 mg of GSK1605786 and to determine TECK/CCL25 and CCR9 expression in colonic mucosa.
-To assess the effect of GSK1605786 on leukocyte migration to the inflamed large intestine and to thymus.
-To explore changes in circulating immune cells following treatment for up to 16 weeks with GSK1605786.
-To explore changes in immune cells present in mucosal biopsies and changes in gene and protein expression in blood and in mucosal biopsies from large bowel following treatment for up to 12 weeks with GSK1605786.

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

In an optional sub-study conducted at designated centres, 99mTc-HMPAO labelling of enriched T lymphocyte populations followed by SPECT scanning will be carried out at baseline and after 28 days repeat dosing (no separate protocol for this sub-study).

E.3

Principal inclusion criteria

1. Male or female aged 18 and over at the time of signing the informed consent.
2. A female subject of child-bearing potential is eligible to participate if she agrees to use one of the contraception methods listed in Section 8.1 for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until completion of the follow-up visit.
3. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form, prior to any of the screening procedures including discontinuation of prohibited medication.
4. At screening (visit 1): patients with a clinical history and examination suggestive of active UC for at least 3 months despite at least 2 weeks treatment with oral >2.4g/day mesalazine / mesalamine or equivalent.
5. At screening/randomization (visit 2):
•Presence of active UC spread beyond the rectum (inflammation extending ≥ 15cm from anal verge) as evidenced by flexible sigmoidoscopy or colonoscopy during the screening window.
•AND MAYO score of 5 – 10 inclusive.
6. AST and ALT < 2xULN; alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).

E.4

Principal exclusion criteria

A subsject will not be eligible in this study if any of the following citeria apply:
1. If female, is pregnant, has a positive pregnancy test or is breast-feeding.
2. Confirmed diagnosis of celiac disease, those who follow a gluten-free diet to manage symptoms of suspected celiac disease and subjects with positive serologic test for Tissue Transamininase, tTG.
3. Subjects who have received immunisation with a live vaccine e.g. measles, mumps, rubella (each as MMR vaccine), oral polio, varicella, yellow fever, within 4 weeks of screening throughout the study, with the exception of influenza vaccine.
4. Known or suspicion of CD, indeterminate colitis, microscopic colitis, ischaemic colitis or radiation-induced colitis, based on medical history, endoscopy and/or histological findings.
5. Subjects with imminent need for surgery for UC in the opinion of the investigator.
6. Subjects where assessment of MAYO score is likely to be confounded by previous surgery (for example colectomy, ileostomies, colostomies or rectal pouches).
7. Subjects requiring enteral or parenteral feeding.
8. Use of prohibited medications within their specified timeframes (see Section 9).
•5-Aminosalicylic acid enema: within 2 weeks of screening and throughout study
•Topical (suppository) 5-Aminosalicylic acid: at screening and throughout study
•Biologic use: within 12 weeks of screening and throughout study
•Corticosteroids use: Oral, rectal or parenteral corticosteroids within 4 weeks of screening and throughout study
•Antibiotics: Intravenous antibiotics within 8 weeks of screening and throughout study (oral antibiotics are permitted where they have been used for >4 weeks with stable dose for ≥2 weeks prior to screening)
•Probiotics: within 4 weeks of screening (patients who initiated probiotics or prebiotics more than 4 weeks prior to screening should continue use throughout study)
•NSAIDs: Within 7 days of screening and throughout the study (except low dose aspirin (≤325 mg/day) which may be continued for cardioprotection)
•Digoxin: or related cardiac glycoside (e.g. digitoxin, deslanoside, lanatoside C, metildigoxin) use at any time during screening and throughout the study.
9. Known HIV infection
10. A positive HBsAg, Anti-HBc, or Hepatitis C antibody result at screening or documented positive result within 3 months of screening.
11. Known varicella, herpes zoster, or other severe viral infection within 6 weeks of screening.
12. Active or latent tuberculosis (TB) infection:
•The subject has a history of TB disease or latent TB infection, in the absence of documented adequate therapy for same.
•Suspicion of current TB disease (including extra pulmonary TB disease such as tuberculosis enteritis) or latent tuberculosis infection, as evidenced by positive QuantiFERON-TB Gold test, or T-SPOT.TB test.
13. Current or chronic history of liver disease or known hepatic or biliary abnormalities including primary sclerosing cholangitis (with the exception of Gilbert’s syndrome or asymptomatic gallstones).
14. QTc ≥450 msec (≥480msec for those with Bundle Branch Block).
•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.
•based on single QTc value of ECG obtained over a brief recording period.
15. 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, congential or acquired immunodeficiency, renal, hepatic, pulmonary, endocrine, metabolic, gastrointestinal, haematologic, or neurological condition or mental impairment).
16. The subject has current evidence of, or has been treated for a malignancy within the past 5 years (other than localised basal cell, squamous cell skin cancer, cervical dysplasia, or cancer in situ that has been resected).
17. Use of any investigational drug within 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer) prior to screening
18. Medical history of sensitivity to any of the components of GSK1605786 (microcrystalline cellulose, colloidal silicon dioxide, crospovidone, magnesium stearate, gelatin).
19. Prior exposure to GSK1605786: Any previous exposure to GSK1605786 (formerly ChemoCentryx compound CCX282-B).
20. Known positive stool culture for enteric pathogens,
21. Positive immunoassay for C. difficile.
22. Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period (with the exception of subjects involved in the optional scintigraphy sub-study, where no more than 700 mL of blood will be collected over the duration of the study, including any extra assessments that may be required).

E.5 End points

E.5.1

Primary end point(s)

•Ordinal response (remission, response, or no response) to treatment as assessed by the MAYO score at week 12.

E.5.1.1

Timepoint(s) of evaluation of this end point

MAYO score assessment during the screening (from – 30 days to -1 day before the start of the treatment phase) and at week 12 during the treatment phase.

E.5.2

Secondary end point(s)

•Safety and tolerability as determined by:
1 - Adverse events (AEs);
2 - Treatment effects on blood pressure, heart rate, electrocardiography (ECG) parameters and haematology, clinical chemistry and urinalysis findings.
• Incidence of remission (MAYO score ≤ 2 with no individual subscale exceeding 1).
• Incidence of response (MAYO score decreased for ≥ 3 points in comparison with baseline).
• Incidence of endoscopic remission (mucosal healing) rate at Week 12, defined as proportion of patients with endoscopy score of 0 or 1 on the MAYO endoscopic subscale.

E.5.2.1

Timepoint(s) of evaluation of this end point

• Adverse events (AEs); Treatment effects on blood pressure, heart rate, electrocardiography (ECG) parameters and haematology, clinical chemistry and urinalysis findings up to and including week 20.
• Incidence of remission (MAYO score ≤ 2 with no individual subscale exceeding 1) at Week 12.
• Incidence of response (MAYO score decreased for ≥ 3 points in comparison with baseline) at Week 12.
• Incidence of endoscopic remission (mucosal healing) rate at Week 12.

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

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Biomarker

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.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the 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

E.8.6.2

Trial being conducted completely outside of the EEA

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 months

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)

Subjects will not receive any additional treatment from GSK after completion of the study because the indication being studied is not life threatening or seriously debilitating and other licensed treatments are available for this patient population. The investigator is responsible for ensuring that consideration has been given to the poststudy care of the patient’s medical condition, whether or not GSK is providing specific post-study treatment.

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

2011-10-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-02-15

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-01-17

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