Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GSK3117391 in Subjects With Rheumatoid Arthritis

NCT02965599 | Terminated Phase 2 Results

• 2 other identifiers: 2049572015-005800-27
• Study Type: interventional
• Target: 3
• Locations: 2 countries
• Sites: 5

Brief Summary

GSK3117391 has the potential to complement existing therapies in the treatment of chronic inflammatory disorders such as rheumatoid arthritis (RA). This study will evaluate the efficacy, safety and tolerability of oral GSK3117391 (Dose A) administered to subjects with severe RA despite treatment with disease-modifying anti-rheumatic drugs (DMARDs). This is a randomised, double-blind (sponsor open), multicentre, placebo-controlled, parallel group study. The total maximum study duration is approximately 10 weeks. Following a screening period of up to 28 days, subjects will be randomized (1:1) to placebo or GSK3117391 (Dose A) administered orally for a period of 28 days. Subjects will be followed up for 7 to 14 days post final dose. Approximately 40 subjects with severe RA will be randomised into the study.

Conditions

Arthritis, Rheumatoid

Keywords

pharmacodynamics; tolerability; GSK3117391; safety; efficacy; rheumatoid arthritis; pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Disease Activity Score for 28 Different Joints With (DAS28) C-reactive Protein (CRP) at Day 28

  The DAS28 score is a derived measurement with differential weighing given to each component as: Tender/Painful Joint Count (TJC28) and swollen joint count (SJC28) both scored 0-28 (higher scores indicate higher disease activity), CRP measured in milligrams per liter and Patient's Global Assessment of Arthritis (PtGA) (visual analogue scale with values from 0 \[best\] to 100 \[worst\]). The formula used to calculate DAS28 score was 0.56 multiplied by square root of TJC28 plus 0.28 multiplied by square root of SJC28 plus 0.36 log of (CRP plus 1) plus 0.014 multiplied by PtGA plus 0.96. DAS28 scores ranged from 0 (best) to 10 (worst). A negative change from Baseline value indicated improvement. Baseline was defined at Day 1 (pre-dose). Change from Baseline was post-baseline value minus the value at Baseline. Safety Population consisted of all participants who received at least one dose of study medication. Individual participant data at Day 28 has been presented.

  Baseline (pre-dose, Day 1) and Day 28

Secondary Outcomes (28)

• Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs

  Up to Day 44

• Number of Participants With Vital Signs Values of Potential Clinical Importance (PCI)

  Up to Day 44

• Number of Participants With Abnormal Electrocardiogram (ECG) Findings

  Up to Day 44

• Number of Participants With Values for Clinical Chemistry Parameters of PCI

  Up to Day 44

• Number of Participants With Values for Hematology Parameters of PCI

  Up to Day 44

Study Arms (2)

GSK3117391

EXPERIMENTAL

Subjects will receive GSK3117391 (Dose A) for 28 days.

Drug: GSK3117391

Placebo

PLACEBO COMPARATOR

Subjects will receive placebo for 28 days.

Drug: Placebo

Interventions

GSK3117391 DRUG

GSK3117391 (Dose A) is a white, opaque, gelatin capsule.

GSK3117391

Placebo DRUG

Placebo is a white, opaque, gelatin capsule.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>=18 years at the time of signing the informed consent.
• The subject must have a diagnosis of RA according to the 2010 ACR/ European League Against Rheumatism (EULAR) classification criteria for RA.
• Functional class I, II or III defined by the 1992 ACR Classification of Functional Status in RA
• The subject must have a EULAR DAS 28-CRP of greater than 5.1 at screening.
• Disease duration of \>6 months (time from onset of patient-reported symptoms of either pain or stiffness or swelling in hands, feet or wrists).
• Swollen joint count of \>=6 (66-joint count) and tender joint count of \>=8 (68-joint count) at screening and at day 1
• The subject must have a CRP serum level of \>=5 mg/L at screening
• The subject has had an inadequate response or intolerance of DMARDs (due to lack of efficacy or toxicity, after at least 8 weeks treatment).
• Body weight \>=45 kilograms (kg) and body mass index (BMI) within the 18.5 - 35 kg/square metre (m\^2) inclusive.
• Male or female requirements. Males: Male subjects with female partners of child bearing potential must comply with contraception requirements from the time of first dose of study medication 91 days after the last dose of study medication. In addition, male subjects must not donate sperm for 91 days after the last dose of study medication.
• Females: A female subject is eligible to participate if she is not pregnant (as confirmed by a negative human chorionic gonadotrophin \[hCG\] test), not lactating, and at least one of the following conditions applies:
• Non-reproductive potential defined as pre-menopausal females with one of the following: documented tubal ligation; documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion; hysterectomy; documented Bilateral Oophorectomy. Postmenopausal defined as 12 months of spontaneous amenorrhea.
• Females of reproductive potential must have proper and established use of a Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) from 28 days prior to the first dose of study medication and until 15 weeks after the last dose of study medication and completion of the follow-up visit. In addition, subjects will be required to utilise a barrier method of contraception. A negative HCG pregnancy test, (serum at screening visit and urine for subsequent visits) with a sensitivity of at least 25 international units per litre \[IU/L\]) is required at the screening visit, between Day -7 to -4 and on Day 1 prior to dose administration. Further pregnancy tests are required at the weekly study visits and the follow-up visit.
• Capable of giving signed informed consent that includes compliance with the requirements and restrictions listed in the consent form and in the protocol.

You may not qualify if:

• Pregnant or lactating women.
• Subjects who meet diagnostic criteria for any other rheumatic disease (example \[eg\], lupus erythematosus, gout, psoriatic arthritis).
• Subjects who have previously been treated with more than 1 biologic agent (such as TNF inhibitors eg. adalimumab, etanercept, infliximab, certolizumab, golimumab or non-TNF inhibitors eg. abatacept, rituximab, tociluzimab) or any investigational biologic.
• Subjects with past history of granulomatous disease eg. leprosy, sarcoidosis.
• Subjects with current symptoms of severe, progressive, or uncontrolled renal, hepatic, haematological (including clotting disorders), gastrointestinal (including gastrooesophageal ulcers), pulmonary, cardiac (including ischemic heart disease), neurological, or cerebral disease, or other medical conditions that, in the opinion of the Investigator, might place the subject at unacceptable risk for participation in this study.
• Subjects with any values for monocytes are below the lower limit of normal (LLN) at screening.
• Haemoglobin \<11 grams (g)/decilitre (dL); haematocrit \<30%, white blood cell count \<=3,000/cubic millimeter (mm\^3) (\<=3.0 x 10\^9/litre \[L\]) or \>=14,000/mm\^3 (\>=14 x 10\^9/L); platelet count \<= 100,000/microlitre (μL) (\<=100x10\^9/L); absolute neutrophil count \<=2x10\^9/L; lymphocyte count \<1x10\^9/L at screening.
• Alanine transaminase (ALT) and bilirubin \>1.5xupper limit of normal (ULN) (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%) at screening.
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• Corrected QT interval (QTc) by Fridericia's correction formula (QTcF) or QTc by Bazett's correction formula (QTcB) \>450 milliseconds (msec) (based on the average of triplicate electrocardiograms \[ECGs\]) at screening.
• Abnormal findings on ECG considered clinically significant by the investigator.
• A history of carcinoma in situ and malignant disease, except for adequately treated non-invasive cancers of the skin (basal or squamous cell) or carcinoma in situ of the uterine cervix.
• Hereditary or acquired immunodeficiency disorder, including immunoglobulin deficiency.
• Abnormal chest X-ray within 12 weeks of Day 1 (locally read and reported by a radiologist) judged by the investigator as clinically-significant.
• History of infected joint prosthesis at any time, with the prosthesis still in situ. History of leg ulcers, catheters, chronic sinusitis or recurrent chest or urinary tract infections.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (5)

GSK Investigational Site

Bialystok, 15-879, Poland

Location

GSK Investigational Site

Elblag, 82-300, Poland

Location

GSK Investigational Site

Świdnik, 21-040, Poland

Location

GSK Investigational Site

Warsaw, 04-305, Poland

Location

GSK Investigational Site

Târgu Mureş, 540327, Romania

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2016
• First Posted: November 17, 2016
• Study Start: December 27, 2016
• Primary Completion: November 14, 2017
• Study Completion: November 14, 2017
• Last Updated: October 30, 2020
• Results First Posted: March 26, 2019

Record last verified: 2020-10

Locations

PL (4); RO (1)