A multicentre, randomised, double-blind (sponsor-unblinded), placebo-controlled study with open label extension to investigate the safety and tolerability, pharmacokinetics, pharmacodynamics, and efficacy of GSK2982772 in subjects with active ulcerative colitis

• Register: EUCTR
• Last refreshed on: 13 July 2020
• Main ID: EUCTR2016-001833-29-SE
• Date of registration: 19/07/2016
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline Research & Development Ltd
• Public title: A multicentre, randomised, double-blind (sponsor-unblinded), placebo-controlled study with open label extension to investigate the safety and tolerability, pharmacokinetics, pharmacodynamics, and efficacy of GSK2982772 in subjects with active ulcerative colitis
• Scientific title: A multicentre, randomised, double-blind (sponsor-unblinded), placebo-controlled study with open label extension to investigate the safety and tolerability, pharmacokinetics, pharmacodynamics, and efficacy of GSK2982772 in subjects with active ulcerative colitis.
• Date of first enrolment: 07/09/2016
• Target sample size: 48
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-001833-29
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Germany, Netherlands, Poland, Russian Federation, Sweden, United Kingdom, United States

Contacts

• Name: GSK Clinical Support Help Desk
• Affiliation: GlaxoSmithKline Research & Development Ltd

• Name: GSK Clinical Support Help Desk
• Affiliation: GlaxoSmithKline Research & Development Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
AGE
1. Between 18 and 75 years of age inclusive, at the time of signing the informed consent.

TYPE OF SUBJECT AND DIAGNOSIS INCLUDING DISEASE SEVERITY
2. Subjects that do not have any medical conditions, other than active UC, that in the opinion of the Investigator put the subject at unacceptable risk or interfere with study assessments or integrity of the data. These medical conditions should be stable at the time of screening and are expected to remain stable for the duration of the study.
3. Subject has had a confirmed diagnosis of active UC, as documented by complete diagnostic colonoscopy to the terminal ileum (TI) with biopsy performed = 3 months prior to screening. If diagnostic colonoscopy was not performed to the TI, it must be documented by the PI that the subject has diffuse inflammation from the rectum extending proximally to the colon in a continuous and uniform way.
4. A Complete Mayo Score of =3 points and endoscopy sub score of 2 to 3 at screening, despite concurrent treatment with at least 1 of the following (oral corticosteroids or any oral 5-aminosalicylates (5-ASA) or purine analogues or all as defined below):
a. Oral 5-ASA at a stable dose (equivalent to = 2.4 g/day of Asacol) for at least 4 weeks prior to first dose. Must remain on a stable dose until end of treatment.
b. Purine analogues (azathioprine, mercaptopurine, thiopurines) or methotrexate for at least12 weeks prior to first dose. Must remain on a stable dose until end of treatment.
c. Stable low dose oral corticosteroid (up to 20 mg prednisolone or equivalent) for 2 weeks prior to sigmoidoscopy. Must remain on a stable dose until end of treatment.
5. If on rectal 5-ASA or corticosteroids, must remain on a stable dose for at least 4 weeks prior to first dose. Must remain on stable dose until the end of treatment.
6. Subject is naive to any biological therapies for UC.
OR
Subject may have had previous exposure to a single anti-TNF biologic agent which was discontinued for reasons other than primary non-response more than 8 weeks (or 5 half lives whichever is longer) prior to first dose.
OR
Subject may have had previous exposure to a single biologic agent (e.g.,
vedolizumab) in the context of a previous clinical trial. The biologic agent must have been discontinued more than 8 weeks (or 5 half lives whichever is longer) prior to first dose.

Note: Exposure to a single biologic agent is not required in addition to Inclusion #4 and #5 above.

WEIGHT
7. A body mass index (BMI) within range of 18.5 – 35 kg/m2 (inclusive) at screening.

SEX
8. Male and female subjects:

Males:
Male subjects with female partners of child bearing potential must comply with the following contraception requirements in Appendix 6.

Females:
A female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotrophin (hCG) test), not lactating, and at least
one of the following conditions applies:
a. Non-reproductive potential as defined in Appendix 6.
b. Reproductive potential and agrees to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) (see Appendix 6) from 30 days prior to the first dose of study medication and until at least 2 days after the last dose of study medication and completion of the follow-up visit.
The Investigator is responsible for ensuring that subjects understand how to properly u
Exclusion criteria:
CONCURRENT CONDITIONS/MEDICAL HISTORY
1.Subject with diagnosis of indeterminate colitis, Crohn’s Disease, infectious colitis, or ischemic colitis
2.Subject with fulminant UC, or UC limited to the rectum
3.Subject with previous small bowel or colonic surgery (with exception of
appendectomy), histological evidence of colonic dysplasia or bowel stricture.
4.Subject with colostomy, fistulae or known symptomatic stenosis of the intestine
5.Subject with toxic megacolon
6.Subject with positive Clostridium difficile toxin test or active/previous colonic CMV infection
7.Subject with current history of suicidal ideation behaviour as measures using the Columbia Suicide Severity Rating Scale or history of attempted suicide
8.An active infection, or a history of infections as follows:
-Hospitalisation for treatment of infection within 60 days before first dose
-Currently on any suppressive therapy for a chronic infection
-Use of parenteral intramu antibiotics for an infection within 60 days before first dose
-A history of opportunistic infections within 1 year of screening. This does not include infections that may occur in immunocompetent individuals, such as fungal nail infections or vaginal candidiasis, unless it is of an unusual severity or recurrent nature
-Recurrent or chronic infection or other active infection that, in the opinion of the Investigator might cause this study to be detrimental to the patient
-History of TB, irrespective of treatment status
-A positive diagnostic TB test at screening defined as a positive
QuantiFERON-TB Gold test or T-spot test. In cases where the QuantiFERON
or T-spot test is indeterminate, the subject may have the test repeated once, but they will not be eligible for the study unless the second test is negative. In cases where the QuantiFERON or T-spot test is positive, but a follow-up chest x-ray, locally read by a radiologist, shows no evidence of current or previous pulmonary tuberculosis, the subject may be eligible for the study at the discretion of the Investigator and GSK Medical Monitor
9. QTc > 450msec or QTc > 480msec for subjects with bundle branch block at screening.
The QTc is the QT interval corrected for heart rate according to either Bazett’s formula (QTcB), Fridericia’s formula (QTcF), or another method, machine or manual over read.
The specific formula that will be used to determine eligibility and discontinuation for an individual subject should be determined prior to initiation of the study. In other words, several different formulae cannot be used to calculate the QTc for an individual subject and then the lowest QTc value used to include or discontinue the subject from the trial. For purposes of data analysis, QTcB, QTcF, another QT correction formula, or a composite of available values of QTc will be used as
specified in the Reporting and Analysis Plan (RAP).
10.ALT >2xULN and bilirubin >1.5xULN at screening
11.Current active or chronic history of liver or biliary disease
12.Current or history of renal disease or estimated glomerular filtration rate by Chronic Kidney Disease Epidemiology Collaboration equation calculation <60 mL/min/1.73m2 at screening
13. Hereditary or acquired immunodeficiency disorder, including immunoglobulin deficiency unless subject has a documented history of selective IgA deficiency
14. A major organ transplant or hematopoietic stem cell/marrow transplant
15.Any planned surgical procedure during the study
16.A history of malignant ne

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Active ulcerative colitis
MedDRA version: 20.0 Level: HLGT Classification code 10017969 Term: Gastrointestinal inflammatory conditions System Organ Class: 10017947 - Gastrointestinal disorders

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Name: GSK2982772
Product Code: GSK2982772
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Not Available
CAS Number: Not Availabl
Current Sponsor code: GSK2982772
Other descriptive name: GSK2982772A, where A denotes the free base
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 30-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: To investigate the safety and tolerability of 60 mg three times daily doses of GSK2982772 in subjects with moderate to severe ulcerative colitis.

Primary end point(s): The primary objective is to investigate safety and tolerability of 60 mg twice daily doses of GSK2982772 in subjects with active ulcerative colitis.

Timepoint(s) of evaluation of this end point: Days 1, 15, 29, 43, 57, 71 and 85.

Secondary Objective: -To investigate the preliminary efficacy of 60 mg three times daily doses of GSK2982772 in achieving mucosal healing after 6 and 12 weeks of
treatment in subjects with active ulcerative colitis.
-To investigate the effect of 60 mg three times daily doses of GSK2982772 on biomarkers of disease activity in subjects with active ulcerative colitis.
-To investigate the effect of 60 mg three times daily doses of GSK2982772 on histologic disease activity in subjects with active ulcerative colitis.
-To investigate the effect of 60 mg three times daily doses of GSK2982772 in achieving clinical response and remission after 6 and 12 weeks of treatment in subjects with active ulcerative colitis.
-To investigate the preliminary efficacy of 60 mg three times daily doses of GSK2982772 in achieving symptomatic clinical remission after 6 and 12 weeks of treatment in subjects with active ulcerative colitis.
- Refer Protocol for further points in Secondary objectives of the trial.

Secondary Outcome(s)

Secondary end point(s): The secondary end points are: To investigate the effect of 60 mg twice daily doses on the pharmacokinetics, mucosal healing, clinical response and remission, histological disease activity, and inflammatory biomarkers

Timepoint(s) of evaluation of this end point: Days 1, 43 and 85.

Secondary ID(s)

202152

Source(s) of Monetary Support

GlaxoSmithKline Research & Development Ltd

Ethics review

Status: Approved
Approval date: 07/09/2016
Contact:

Results

• Results available: Yes
• Date Posted: 03/06/2020
• Date Completed: 17/06/2019
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-001833-29/results