Efficacy and Safety of GSK3196165 Versus Placebo and Tofacitinib in Participants With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate

NCT03980483 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: 201790
• Study Type: interventional
• Target: 1,537
• Locations: 10 countries
• Sites: 76

Brief Summary

This study \[contRAst 1 (201790: NCT03980483)\] is a phase 3, randomized, multicenter, double blind study to assess the safety and efficacy of GSK3196165, in combination with methotrexate (MTX), for the treatment of adult participants with moderate to severe active rheumatoid arthritis (RA) who have had an inadequate response to MTX. The study will consist of a screening phase of up to 6 weeks followed by a 52-week treatment phase in which participants will be randomized in a ratio of 6:6:3:1:1:1 to receive GSK3196165 150 milligrams (mg) subcutaneous (SC) weekly, GSK3196165 90 mg SC weekly, tofacitinib capsules (cap) 5 mg twice a day or placebo (three arms, each placebo arm will have 12 weeks placebo followed by 40 weeks active treatment) respectively, all in combination with MTX. Participants who, in investigator's judgement will benefit from extended treatment with GSK3196165, may be included in the long-term extension study \[contRAst X (209564: NCT04333147)\]. For those participants who do not continue into the long term-extension study, there will be an 8 week safety follow-up visit following the treatment phase.

Conditions

Arthritis, Rheumatoid

Keywords

Rheumatoid arthritis; GSK3196165; Otilimab; Tofacitinib; Methotrexate; Placebo

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Achieving 20 Percentage (%) Improvement in American College of Rheumatology Criteria (ACR20) at Week 12 Superiority Comparison With Placebo

  ACR20 is calculated as a 20% improvement from Baseline in Tender Joint Count 68 (TJC68) and Swollen Joint Count 66 (SJC66) and a 20% improvement in 3 of the following 5 measures: Patient's Global Assessment of Arthritis Disease Activity (PtGA) \[visual analogue scale (VAS) with values from 0=best to 100=worst\], Physician Global Assessment of Arthritis Disease Activity (PhGA) (VAS with values from 0=best to 100=worst), Patient Assessment of Arthritis Pain (VAS with values from 0=no pain and 100=most severe pain), Health Assessment Questionnaire-Disability Index (HAQ-DI) (ranges from 0 to 3 where 0 = least difficulty and 3 = extreme difficulty) and an acute-phase reactant \[high sensitivity C-reactive Protein milligram per liter (mg/L) (hsCRP)\]. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

  Week 12

Secondary Outcomes (97)

• Percentage of Participants Achieving Clinical Disease Activity Index (CDAI) Total Score Less Than or Equal to (<=)10 [CDAI Low Disease Activity (LDA)] at Week 12

  Week 12

• Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12

  Baseline (Day 1) and Week 12

• Percentage of Participants Achieving 20% Improvement in ACR20 at Week 24 (Non-Inferiority Versus Tofacitinib)

  Week 24

• Percentage of Participants Achieving 50%/70% Improvement in American College of Rheumatology Criteria (ACR50/70) at Week 24 and ACR 20/50/70 at and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

  Week 24 and Week 52

• Percentage of Participants Achieving ACR20/50/70 at Week 24 and Week 52 for Placebo Switched Arms

  Week 24 and Week 52

Study Arms (6)

GSK3196165 90mg + MTX

EXPERIMENTAL

Participants received GSK3196165 90 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with methotrexate (MTX).

Biological: GSK3196165 (Otilimab)

GSK3196165 150mg + MTX

EXPERIMENTAL

Participants received GSK3196165 150 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with MTX.

Biological: GSK3196165 (Otilimab)

Tofacitinib 5mg + MTX

ACTIVE COMPARATOR

Participants received Tofacitinib 5mg capsule, orally, twice daily (BID) in combination with MTX plus placebo injection weekly to maintain the blind for 52 weeks.

Drug: Tofacitinib 5 mg

Placebo + MTX and GSK3196165 90mg + MTX

PLACEBO COMPARATOR

Participants received Placebo weekly SC injection in combination with MTX for 12 weeks. At Week 12, participants were switched from placebo to GSK3196165 90 mg, SC injection, once weekly in combination with MTX until Week 52.

Biological: GSK3196165 (Otilimab); Drug: Placebo

Placebo + MTX and GSK3196165 150mg + MTX

PLACEBO COMPARATOR

Participants received Placebo weekly SC injection in combination with MTX for 12 weeks. At Week 12, participants were switched from placebo to GSK3196165 150 mg, SC injection, once weekly in combination with MTX until Week 52.

Biological: GSK3196165 (Otilimab); Drug: Placebo

Placebo + MTX and Tofacitinib 5mg + MTX

PLACEBO COMPARATOR

Participants received Placebo capsule weekly in combination with MTX for 12 weeks. At Week 12, participants were switched from placebo capsule to Tofacitinib 5mg, capsule, orally, BID in combination with MTX plus placebo injection to maintain the blind for 52 weeks.

Drug: Tofacitinib 5 mg; Drug: Placebo

Interventions

GSK3196165 (Otilimab) BIOLOGICAL

GSK3196165 solution in vial/pre-filled syringe (PFS) to be administered SC.

GSK3196165 150mg + MTX; GSK3196165 90mg + MTX; Placebo + MTX and GSK3196165 150mg + MTX; Placebo + MTX and GSK3196165 90mg + MTX

Tofacitinib 5 mg DRUG

Tofacitinib cap (over encapsulated 5mg tablet) to be administered orally.

Placebo + MTX and Tofacitinib 5mg + MTX; Tofacitinib 5mg + MTX

Placebo DRUG

Placebo sterile 0.9 percentage (%) weight by volume (w/v) sodium chloride solution in vial/pre-filled syringe (PFS) to be administered SC.

Placebo + MTX and GSK3196165 150mg + MTX; Placebo + MTX and GSK3196165 90mg + MTX

Eligibility Criteria

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

You may qualify if:

• \>=18 years of age
• Has had RA for \>=6 months and was not diagnosed before 16 years of age
• Has active disease, as defined by having both:\*
• \>=6/68 tender/painful joint count (TJC), and
• \>=6/66 swollen joint count (SJC)
• Has at least 1 bone erosion present on hand/wrist or foot radiographs
• Has had an inadequate response to MTX, despite currently taking MTX 15-25 mg/week\*\* oral or injected
• If surgical treatment of a joint has been performed, that joint cannot be counted in the TJC or SJC.
• A lower dose of 7.5 mg/week is acceptable if reduced for reasons of intolerance to MTX or per local requirement.

You may not qualify if:

• Has had any active and/or recurrent infections (excluding recurrent fungal infections of the nail bed) or has required management of acute or chronic infections.
• Has received prior treatment with an antagonist of GM-CSF or its receptor or Janus kinase (JAK) inhibitors (either experimental or approved)
• Has received prior treatment with a biologic Disease-modifying antirheumatic drug (DMARD) which has been discontinued due to an inadequate response.

Sponsors & Collaborators

• GlaxoSmithKline: lead
• Iqvia Pty Ltd: collaborator

Study Sites (76)

GSK Investigational Site

Bengbu, Anhui, 233004, China

Location

GSK Investigational Site

Pingxiang, Jiangxi, 337055, China

Location

GSK Investigational Site

Changchun, Jilin, 130021, China

Location

GSK Investigational Site

Chengdu, Sichuan, 610041, China

Location

GSK Investigational Site

Shanghai, 200052, China

Location

GSK Investigational Site

Baja, 6500, Hungary

Location

GSK Investigational Site

Balatonfüred, 8230, Hungary

Location

GSK Investigational Site

Budapest, 1023, Hungary

Location

GSK Investigational Site

Budapest, 1033, Hungary

Location

GSK Investigational Site

Budapest, 1036, Hungary

Location

GSK Investigational Site

Kistarcsa, 2143, Hungary

Location

GSK Investigational Site

Szentes, 6600, Hungary

Location

GSK Investigational Site

Székesfehérvár, 8000, Hungary

Location

GSK Investigational Site

Veszprém, H-8200, Hungary

Location

GSK Investigational Site

Ahmedabad, 380005, India

Location

GSK Investigational Site

Ahmedabad, 380013, India

Location

GSK Investigational Site

Ahmedabad, 380016, India

Location

GSK Investigational Site

Ahmedabad, 380054, India

Location

GSK Investigational Site

Banglore, 560070, India

Location

GSK Investigational Site

Belagavi, 590010, India

Location

GSK Investigational Site

Hubli, 580021, India

Location

GSK Investigational Site

Hyderabad, 500018, India

Location

GSK Investigational Site

Jaipur, 302001, India

Location

GSK Investigational Site

Jaipur, 302006, India

Location

GSK Investigational Site

Kolkata, 700020, India

Location

GSK Investigational Site

Nagpur, 440009, India

Location

GSK Investigational Site

Nagpur, 440012, India

Location

GSK Investigational Site

Nashik, 422005, India

Location

GSK Investigational Site

Nashik, 422101, India

Location

GSK Investigational Site

New Delhi, 110060, India

Location

GSK Investigational Site

Pimpri-Chinchwad, 411033, India

Location

GSK Investigational Site

Pune, 411004, India

Location

GSK Investigational Site

Pune, 411057, India

Location

GSK Investigational Site

Rajkot, 360005, India

Location

GSK Investigational Site

Surat, 395002, India

Location

GSK Investigational Site

Vadodara, 390001, India

Location

GSK Investigational Site

Verona, Veneto, 37126, Italy

Location

GSK Investigational Site

Klang, 41200, Malaysia

Location

GSK Investigational Site

Kuala Lumpur, 59100, Malaysia

Location

GSK Investigational Site

Seremban, Negeri Sembilan, 70300, Malaysia

Location

GSK Investigational Site

Sibu, 96000, Malaysia

Location

GSK Investigational Site

Bialystok, 15-351, Poland

Location

GSK Investigational Site

Bydgoszcz, 85-168, Poland

Location

GSK Investigational Site

Częstochowa, 42202, Poland

Location

GSK Investigational Site

Gdansk, 80-382, Poland

Location

GSK Investigational Site

Gdynia, 81-338, Poland

Location

GSK Investigational Site

Gdynia, 81-537, Poland

Location

GSK Investigational Site

Katowice, 40-040, Poland

Location

GSK Investigational Site

Katowice, 40-282, Poland

Location

GSK Investigational Site

Krakow, 30-363, Poland

Location

GSK Investigational Site

Lodz, 90-127, Poland

Location

GSK Investigational Site

Lublin, 20-362, Poland

Location

GSK Investigational Site

Lublin, 20-582, Poland

Location

GSK Investigational Site

Nowa Sól, 67-100, Poland

Location

GSK Investigational Site

Olsztyn, 10-117, Poland

Location

GSK Investigational Site

Poznan, 60-529, Poland

Location

GSK Investigational Site

Poznan, 60-702, Poland

Location

GSK Investigational Site

Poznan, 60-773, Poland

Location

GSK Investigational Site

Sochaczew, 96-500, Poland

Location

GSK Investigational Site

Staszów, 28-200, Poland

Location

GSK Investigational Site

Torun, 87-100, Poland

Location

GSK Investigational Site

Warsaw, 00-465, Poland

Location

GSK Investigational Site

Warsaw, 00-874, Poland

Location

GSK Investigational Site

Warsaw, 01-192, Poland

Location

GSK Investigational Site

Warsaw, 02-118, Poland

Location

GSK Investigational Site

Warsaw, 02-673, Poland

Location

GSK Investigational Site

Wroclaw, 50-381, Poland

Location

GSK Investigational Site

Zamość, 22-400, Poland

Location

GSK Investigational Site

Moscow, 115522, Russia

Location

GSK Investigational Site

Belgrade, 11000, Serbia

Location

GSK Investigational Site

A Coruña, 15006, Spain

Location

GSK Investigational Site

Córdoba, 140044, Spain

Location

GSK Investigational Site

Santiago de Compostela, 15706, Spain

Location

GSK Investigational Site

Romford, Essex, RM1 3PJ, United Kingdom

Location

GSK Investigational Site

Northwood, Middlesex, HA6 2RN, United Kingdom

Location

GSK Investigational Site

Kenilworth, Warwickshire, CV8 1JD, United Kingdom

Location

Related Publications (1)

• Fleischmann RM, van der Heijde D, Strand V, Atsumi T, McInnes IB, Takeuchi T, Taylor PC, Bracher M, Brooks D, Davies J, Goode C, Gupta A, Mukherjee S, O'Shea C, Saurigny D, Schifano LA, Shelton C, Smith JE, Wang M, Wang R, Watts S, Weinblatt ME. Anti-GM-CSF otilimab versus tofacitinib or placebo in patients with active rheumatoid arthritis and an inadequate response to conventional or biologic DMARDs: two phase 3 randomised trials (contRAst 1 and contRAst 2). Ann Rheum Dis. 2023 Dec;82(12):1516-1526. doi: 10.1136/ard-2023-224482. Epub 2023 Sep 12.

  PMID: 37699654 BACKGROUND

Related Links

• 209564 contRAst X NCT04333147

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Otilimab; tofacitinib

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 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants will be randomized to one of six intervention arms in ratio of 6:6:3:1:1:1.

Study Record Dates

• First Submitted: May 15, 2019
• First Posted: June 10, 2019
• Study Start: May 16, 2019
• Primary Completion: September 15, 2021
• Study Completion: August 16, 2022
• Last Updated: March 27, 2024
• Results First Posted: October 25, 2023

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

ES (3); RU (1); CN (5); IN (22); MY (4); IT (1); HU (9); PL (27); SE (1); GB (3)