A multicentre, randomised, double-blind (sponsor-unblinded), placebo-controlled study to investigate the safety and tolerability, pharmacokinetics, pharmacodynamics, and efficacy of GSK2982772 in subjects with moderate to severe rheumatoid arthritis.

• Register: EUCTR
• Last refreshed on: 10 December 2019
• Main ID: EUCTR2016-000912-13-DE
• Date of registration: 29/06/2016
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline Research & Development Ltd
• Public title: A multicentre, randomised, double-blind (sponsor-unblinded), placebo-controlled study to investigate the safety and tolerability, pharmacokinetics, pharmacodynamics, and efficacy of GSK2982772 in subjects with moderate to severe rheumatoid arthritis.
• Scientific title: A multicentre, randomised, double-blind (sponsor-unblinded), placebo-controlled study to investigate the safety and tolerability, pharmacokinetics, pharmacodynamics, and efficacy of GSK2982772 in subjects with moderate to severe rheumatoid arthritis.
• Date of first enrolment: 30/08/2016
• Target sample size: 36
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-000912-13
• 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: 2
• 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, Italy, Poland, Romania, Spain, United Kingdom

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 moderate to severe RA, 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 rheumatoid arthritis according to the revised
2010 American College of Rheumatology/European League Against Rheumatism ACR-EULAR classification criteria.
4. Disease duration of = 12 weeks (time from onset of patient-reported symptoms of either pain or stiffness or swelling in hands, feet or wrists) at screening.
5. Swollen joint count of =4 (28-joint count) and tender joint count = 4 (28-joint count) at screening.
6. Subject has a DAS28 CRP disease activity score of = 3.2 and CRP = 5.0 mg/L ( = 4.76 nmol/L) at screening.
7. Subject must have received at least 12 weeks of non-biologic DMARD monotherapy or methotrexate (MTX)/DMARD combination therapy prior to screening AND must be on stable dose throughout the study.
8. Subject is naive to any biological therapies for RA
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) from first dose. Note: Exposure to a single anti-TNF is not required in addition to Inclusion #7 above.
9. For subjects who have consented to synovial joint biopsy:
a. Subject has an involved knee, wrist, or ankle suitable for biopsy, as assessed by a rheumatologist at screening.

WEIGHT
10. A body mass index (BMI) within range of 18.5 - 35 kg/m2 (inclusive) at screening.
SEX
11. 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 30 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 use these methods of contraception.

INFORMED CONSENT
12. Capable of giving signed informed consent as described in Sectio
Exclusion criteria:
CONCURRENT CONDITIONS/MEDICAL HISTORY (INCLUDES LIVER
FUNCTION AND QTc INTERVAL)
1. Subject with a positive anti-double stranded deoxyribonucleic acid and confirmed diagnosis of systemic lupus erythematosus (SLE)
2. Subject with current history of Suicidal Ideation Behaviour (SIB) as measured using the Columbia Suicide Severity Rating Scale (C-SSRS) or a history of attempted suicide
3. 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 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 locally-read follow up chest x-ray, 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
4. 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 and documented 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)
5. ALT >2xULN and bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if
bilirubin is fractionated and direct bilirubin <35%) at screening
6. Current active or chronic history of liver or biliary disease
7. Current or history of renal disease or estimated glomerular filtration rate (GFR) by Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) calculation <60 mL/min/1.73m2 at screening
8. Hereditary or acquired immunodeficiency disorder, including immunoglobulin deficiency
9. A major organ transplant or hematopoietic stem cell/marrow transplant
10. Any planned surgical proce

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

Health Condition(s) or Problem(s) studied

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

subjects with moderate to severe rheumatoid arthritis.
MedDRA version: 20.0 Level: LLT Classification code 10039076 Term: Rheumatoid arthritis and other inflammatory polyarthropathies System Organ Class: 100000004859

Intervention(s)

Product Name: GSK2982772
Product Code: GSK2982772
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Not Available
CAS Number: Not Availabl
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)

Secondary Objective: -To investigate the plasma concentrations of GSK2982772 following 60 mg three times daily doses of GSK2982772 in subjects with moderate to
severe Rheumatoid Arthritis.

-To investigate the effect of 60 mg three times daily doses of GSK2982772 on inflammatory biomarkers in blood subjects with moderate to severe Rheumatoid Arthritis.

-To investigate the effect of 60 mg three times daily doses of GSK2982772 on bone and synovial parameters as measured by MRI and DCE-MRI in subjects with moderate to severe Rheumatoid Arthritis.

-To investigate the effect of 60 mg three times daily doses of GSK2982772 on clinical disease activity in subjects with moderate to severe Rheumatoid Arthritis

-To investigate the effect of 60 mg three times daily dosing of GSK2982772 on methotrexate (MTX) concentrations

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

Primary end point(s): Primary endpoint:
• Adverse events
• Clinical laboratory values (clinical chemistry, haematology and urinalysis)
• Vital sign measurements (blood pressure, heart rate, respiratory rate, and body temperature)
• 12-Lead ECG monitoring.

Timepoint(s) of evaluation of this end point: Days 1, 8, 15, 29, 43, 57, 71 and 85.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Days 1, 8, 15, 29, 43, 57, 71 and 85.

Secondary end point(s): The secondary end points are: To investigate the effect of 60 mg twice daily doses on the pharmacokinetics, inflammatory biomarkers in blood, bone and synovial parameters, disease activity, and methotrexate concentrations.

Secondary ID(s)

203168

Source(s) of Monetary Support

GlaxoSmithKline

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 28/10/2019
• Date Completed: 22/10/2018
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-000912-13/results