A long-term extension study to assess the safety and efficacy of GSK3196165 in the treatment of rheumatoid arthritis.

Phase 1

Conditions: Rheumatoid Arthritis
MedDRA version: 23.1Level: PTClassification code 10039073Term: Rheumatoid arthritisSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Registration Number: EUCTR2019-000878-30-CZ

Lead Sponsor: GlaxoSmithKline Research & Development Limited

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 3000

Inclusion Criteria

1. Participants with rheumatoid arthritis who are aged =18 years at the time of signing informed consent, who have completed one of the qualifying GSK3196165 clinical studies and who, in the opinion of the investigator, may benefit from treatment with
GSK3196165.

2. Body weight = 40kg

3. Male or female participants are eligible to participate as long as they meet the contraceptive eligibility criteria and agree to abide by the
contraceptive requirements.

4. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

5. For participants on MTX: must be willing to continue treatment with oral folic acid (at least 5 mg/week) or equivalent while receiving MTX (mandatory co-medication for MTX treatment).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 2640
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 360

Exclusion Criteria

1.Had study intervention permanently discontinued at any time during a qualifying study except any participant with a new diagnosis of latent TB at the end of study assessment in a qualifying study and currently undertaking or willing to complete at least 4 weeks of anti-TB treatment off study treatment, per WHO or national guidelines prior to re-commencing therapy and complete the remainder of anti-TB treatment while on study.

2.Evidence of latent TB (as documented by a positive QuantiFERON-TB Gold plus test or T-SPOT.TB test, no findings on medical history or clinical examination consistent with active TB, and a normal chest radiograph) except for participants that
oAre currently undertaking or willing to complete at least 4 weeks of anti-TB therapy off study treatment, as per WHO or national guidelines prior to re-commencing study treatment and agree to complete the remainder of anti-TB treatment while in the study OR
oHad documented evidence of satisfactory anti-TB treatment as per WHO or national guidelines following review by a physician specialising in TB on entry to a qualifying study.

3.Current or previous active Mycobacterium tuberculosis (TB) regardless of treatment.

4.Were temporarily discontinued from study intervention at the time of the final study visit of a qualifying study and, in the opinion of the investigator, participation in the extension study poses an unacceptable risk for the patient’s participation.

5.A new cancer or malignancy except for basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix treated and considered cured by the investigator.

6.Have developed any lymphoproliferative disorder during a qualifying study, such as Epstein Barr Virus (EBV) related lymphoproliferative disorder, or signs and symptoms suggestive of current lymphatic disease.

7.Have significant uncontrolled cardiovascular, cerebrovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, or neuropsychiatric disorders, or abnormal laboratory values that developed during a qualifying study that, in the opinion of the investigator, poses an unacceptable risk for the patient’s participation.

PRIOR/CONCOMITANT THERAPY
8.Participants who are expected to be non-compliant with restrictions on medications and vaccinations prior to the study, during the study or during the 8-week safety follow-up of the study. See Section 6.5.2 for details of prohibited medications/treatments and Section 6.5.1 for details of permitted medications/treatments.

PRIOR/CONCURRENT CLINICAL STUDY EXPERIENCE
9.Participants who are currently participating in any interventional clinical study other than a qualifying GSK3196165 clinical study.

DIAGNOSTIC ASSESSMENTS
10.Abnormal chest radiograph within the last 12 weeks judged by the investigator as clinically-significant.

OTHER EXCLUSIONS
11.Pregnant or lactating, or women planning to become pregnant or initiating breastfeeding

12.History of sensitivity to any of the study treatments, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the long-term safety of<br>GSK3196165 at weekly doses of 90 mg or 150 mg for the treatment of participants with moderately to severely active rheumatoid<br>arthritis (RA).;Secondary Objective: -To determine the long-term efficacy of<br>GSK3196165.<br>-To determine effects of GSK3196165 on<br>Patient Reported Outcomes.<br>-To determine the immunogenic potential of<br>GSK3196165.;Primary end point(s): ? Incidence of adverse events (AEs) and<br>serious adverse events (SAEs) and adverse<br>events of special interests (AESI).<br>? Change from baseline in key laboratory<br>parameters.<br>? Proportion of participants with NCI-CTCAE<br>=Grade 3 haematological/;Timepoint(s) of evaluation of this end point: At various time points as defined in the protocol

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Proportion of participants at Weeks 24, 48 and<br>every 48 weeks thereafter, achieving:<br>? CDAI total score =10 (CDAI LDA)<br>? CDAI total score =2.8 (CDAI Remission)<br>? DAS28-CRP <2.6 and DAS28-ESR <2.6<br>(DAS28 remission).<br>? ACR and EULAR Remission (Boolean and<br>SDAI).<br>Absolute values at Weeks 24, 48 and every 48<br>weeks thereafter for:<br>? CDAI total score.<br>? DAS28-CRP & DAS28-ESR.<br>? van der Heijde mTSS score (participants<br>from 201790 and 201791 only);Timepoint(s) of evaluation of this end point: Weeks 24, 48 and every 48 weeks thereafter

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