E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Rheumatoid Arthritis (RA) is a chronic, systemic inflammatory autoimmune disease, characterised by a symmetrical polyarthritis that is associated with substantial disability and morbidity |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039073 |
E.1.2 | Term | Rheumatoid arthritis |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the long-term safety of
GSK3196165 at weekly doses of 90 mg or 150 mg for the treatment of participants with moderately to severely active rheumatoid
arthritis (RA). |
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E.2.2 | Secondary objectives of the trial |
-To determine the long-term efficacy of
GSK3196165.
-To determine effects of GSK3196165 on
Patient Reported Outcomes.
-To determine the immunogenic potential of
GSK3196165. |
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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 |
During the course of this long-term extension study, it is expected that an autoinjector (AI) device will become available. When the AI device becomes available, a sub-study of approximately 200 new participants who join the extension study at this time, will examine AI device usability and steady state PK. |
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E.3 | Principal 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). |
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E.4 | Principal 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
Incidence of adverse events (AEs) and
serious adverse events (SAEs) and adverse
events of special interests (AESI).
Change from baseline in key laboratory
parameters.
Proportion of participants with NCI-CTCAE
≥Grade 3 haematological/ |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At various time points as defined in the protocol |
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E.5.2 | Secondary end point(s) |
Proportion of participants at Weeks 24, 48 and
every 48 weeks thereafter, achieving:
CDAI total score ≤10 (CDAI LDA)
CDAI total score ≤2.8 (CDAI Remission)
DAS28-CRP <2.6 and DAS28-ESR <2.6
(DAS28 remission).
ACR and EULAR Remission (Boolean and
SDAI).
Absolute values at Weeks 24, 48 and every 48
weeks thereafter for:
CDAI total score.
DAS28-CRP & DAS28-ESR.
van der Heijde mTSS score (participants
from 201790 and 201791 only) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Weeks 24, 48 and every 48 weeks thereafter |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity
Optional future scientific research |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 151 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Belgium |
Brazil |
Bulgaria |
Canada |
China |
Colombia |
Czech Republic |
Estonia |
France |
Germany |
Hungary |
India |
Italy |
Japan |
Korea, Republic of |
Latvia |
Lithuania |
Malaysia |
Mexico |
Philippines |
Poland |
Russian Federation |
Serbia |
South Africa |
Spain |
Thailand |
Ukraine |
United Kingdom |
United States |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |