A Study Assessing the Efficacy and Safety of Sarilumab Added to MTX in Japanese Patients With Moderately to Severely Active Rheumatoid Arthritis (SARIL-RA-KAKEHASI)

NCT02293902 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: EFC14059U1111-1155-7401
• Study Type: interventional
• Target: 243
• Locations: 1 country
• Sites: 96

Brief Summary

Primary Objective:

• To demonstrate that sarilumab added to methotrexate (MTX) reduce signs and symptoms of rheumatoid arthritis (RA) in Japanese RA participants with an inadequate response to MTX. Secondary Objective:
• To assess the safety of sarilumab added to MTX in Japanese RA participants with an inadequate response to MTX.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Achieving American College of Rheumatology 20 (ACR20) Response at Week 24

  American College of Rheumatology (ACR) response is a composite rating scale that includes 7 variables: tender joints count (TJC \[68 joints\]); Swollen joints count (SJC \[66 joints\]); levels of an acute phase reactant (high sensitivity C-reactive protein \[hs-CRP level\]); participant's assessment of pain (measured on 0 \[no pain\]-100 mm \[worst pain\] visual analog scale \[VAS\]); participant's global assessment of disease activity (measured on 0 \[no arthritis activity\]-100 mm \[maximal arthritis activity\] VAS); physician's global assessment of disease activity (measured on 0 \[no arthritis activity\]-100 mm \[maximal arthritis activity\] VAS); participant's assessment of physical function (measured by health assessment questionnaire disability index \[HAQ-DI\], with scoring range of 0 \[better health\] - 3 \[worst health\]). ACR20 response was defined as achieving at least 20% improvement in both TJC and SJC, and at least 20% improvement in at least 3 of the 5 other assessments.

  Week 24

Secondary Outcomes (8)

• Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

  For placebo arm: Baseline up to Week 24; For sarilumab 150 mg/150 mg, sarilumab 200 mg/200 mg and sarilumab rescue arm: Baseline up to Week 58; For placebo/sarilumab 150 mg and placebo/sarilumab 200 mg arm: Week 25 up to Week 58

• Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities

  For placebo arm: Baseline up to Week 24; For sarilumab 150 mg/150 mg, sarilumab 200 mg/200 mg and sarilumab rescue arm: Baseline up to Week 58; For placebo/sarilumab 150 mg and placebo/sarilumab 200 mg arm: Week 25 up to Week 58

• Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities

  For placebo arm: Baseline up to Week 24; For sarilumab 150 mg/150 mg, sarilumab 200 mg/200 mg and sarilumab rescue arm: Baseline up to Week 58; For placebo/sarilumab 150 mg and placebo/sarilumab 200 mg arm: Week 25 up to Week 58

• Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Hematological Parameters

  For placebo arm: Baseline up to Week 24; For sarilumab 150 mg/150 mg, sarilumab 200 mg/200 mg and sarilumab rescue arm: Baseline up to Week 58; For placebo/sarilumab 150 mg and placebo/sarilumab 200 mg arm: Week 25 up to Week 58

• Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Metabolic Parameters

  For placebo arm: Baseline up to Week 24; For sarilumab 150 mg/150 mg, sarilumab 200 mg/200 mg and sarilumab rescue arm: Baseline up to Week 58; For placebo/sarilumab 150 mg and placebo/sarilumab 200 mg arm: Week 25 up to Week 58

Study Arms (4)

Sarilumab 150 mg/150 mg

EXPERIMENTAL

Sarilumab 150 mg subcutaneous (SC) injection once every 2 weeks (q2w) in combination with MTX and folic acid in double-blind period up to Week 24 followed by single-blind period in which participants continued with the same treatment up to Week 52. Participants with inadequate response (defined as less than 20% improvement from baseline on 2 consecutive visits \[at least 4 weeks apart\] in either tender joint count \[TJC\] or swollen joint count \[SJC\], or with any other clear lack of efficacy based on investigator's judgment) by Week 16, were rescued with open label sarilumab 200 mg q2w treatment.

Drug: Sarilumab SAR153191 (REGN88); Drug: Methotrexate; Drug: Folic acid

Sarilumab 200 mg/200 mg

EXPERIMENTAL

Sarilumab 200 mg SC injection q2w in combination with MTX and folic acid in double-blind period up to Week 24 followed by single-blind period in which participants continued with the same treatment up to Week 52. Participants with inadequate response (defined as less than 20% improvement from baseline on 2 consecutive visits \[at least 4 weeks apart\] in either TJC or SJC, or with any other clear lack of efficacy based on investigator's judgment) by Week 16, were rescued with open label sarilumab 200 mg q2w treatment.

Drug: Sarilumab SAR153191 (REGN88); Drug: Methotrexate; Drug: Folic acid

Placebo/Sarilumab 150 mg

PLACEBO COMPARATOR

Placebo (for sarilumab) SC injection q2w in combination with MTX and folic acid in double-blind period up to Week 24 followed by a single-blind period in which participants were switched and received sarilumab 150 mg SC injection q2w in combination with MTX and folic acid up to Week 52. Participants with inadequate response (defined as less than 20% improvement from baseline on 2 consecutive visits \[at least 4 weeks apart\] in either TJC or SJC, or with any other clear lack of efficacy based on Investigator's judgment) by Week 16, were rescued with open label sarilumab 200 mg q2w treatment.

Drug: Sarilumab SAR153191 (REGN88); Other: Placebo (for sarilumab); Drug: Methotrexate; Drug: Folic acid

Placebo/Sarilumab 200 mg

PLACEBO COMPARATOR

Placebo (for sarilumab) SC injection q2w in combination with MTX and folic acid in double-blind period up to Week 24 followed by a single-blind period in which participants were switched and received sarilumab 200 mg SC injection q2w in combination with MTX and folic acid up to Week 52. Participants with inadequate response (defined as less than 20% improvement from baseline on 2 consecutive visits \[at least 4 weeks apart\] in either TJC or SJC, or with any other clear lack of efficacy based on Investigator's judgment) by Week 16, were rescued with open label sarilumab 200 mg q2w treatment.

Drug: Sarilumab SAR153191 (REGN88); Other: Placebo (for sarilumab); Drug: Methotrexate; Drug: Folic acid

Interventions

Sarilumab SAR153191 (REGN88) DRUG

Pharmaceutical form: solution for injection Route of administration: subcutaneous

Placebo/Sarilumab 150 mg; Placebo/Sarilumab 200 mg; Sarilumab 150 mg/150 mg; Sarilumab 200 mg/200 mg

Placebo (for sarilumab) OTHER

Pharmaceutical form: solution for injection Route of administration: subcutaneous

Placebo/Sarilumab 150 mg; Placebo/Sarilumab 200 mg

Methotrexate DRUG

Dispensed according to local practice.

Placebo/Sarilumab 150 mg; Placebo/Sarilumab 200 mg; Sarilumab 150 mg/150 mg; Sarilumab 200 mg/200 mg

Folic acid DRUG

Dispensed according to local practice.

Placebo/Sarilumab 150 mg; Placebo/Sarilumab 200 mg; Sarilumab 150 mg/150 mg; Sarilumab 200 mg/200 mg

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of RA, according to the American College of Rheumatology/The European League Against Rheumatism (ACR/EULAR) 2010 Rheumatoid Arthritis Classification Criteria with \>=3 months disease duration.
• Moderately to severely active RA defined as:
• At least 8 of 68 tender joints and 6 of 66 swollen joints at screening visit.
• High sensitivity C-Reactive Protein (hs-CRP) \>=6mg/L at screening visit.

You may not qualify if:

• Participants \<20 or \>75 years of age.
• Treatment with any Disease-modifying antirheumatic drug (DMARD) other than MTX or biologic agent without the appropriate off-drug period prior to screening.
• Prior treatment with anti-interleukin-6 (anti-IL-6) or anti-interleukin-6 receptor (IL-6R) antagonist therapies, including but not limited to tocilizumab or sarilumab.
• The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (96)

Investigational Site Number 392010

Asahi-Shi, Japan

Location

Investigational Site Number 392001

Asahikawa-Shi, Japan

Location

Investigational Site Number 392035

Asahikawa-Shi, Japan

Location

Investigational Site Number 392070

Beppu-Shi, Japan

Location

Investigational Site Number 392036

Chiba, Japan

Location

Investigational Site Number 392083

Chūōku, Japan

Location

Investigational Site Number 392047

Fuchu-Shi, Japan

Location

Investigational Site Number 392004

Fukui-shi, Japan

Location

Investigational Site Number 392007

Fukuoka, Japan

Location

Investigational Site Number 392038

Fukuoka, Japan

Location

Investigational Site Number 392039

Fukuoka, Japan

Location

Investigational Site Number 392078

Fukushima, Japan

Location

Investigational Site Number 392054

Funabashi-Shi, Japan

Location

Investigational Site Number 392015

Hachioji-Shi, Japan

Location

Investigational Site Number 392085

Hannan-Shi, Japan

Location

Investigational Site Number 392091

Hiroshima, Japan

Location

Investigational Site Number 392098

Hiroshima, Japan

Location

Investigational Site Number 392009

Hitachi-Naka, Japan

Location

Investigational Site Number 392011

Hitachi-Naka, Japan

Location

Investigational Site Number 392030

Ichinomiya-Shi, Japan

Location

Investigational Site Number 392002

Iizuka-Shi, Japan

Location

Investigational Site Number 392019

Kagoshima, Japan

Location

Investigational Site Number 392066

Kamakura-Shi, Japan

Location

Investigational Site Number 392086

Kamogawa-Shi, Japan

Location

Investigational Site Number 392050

Kato-Shi, Japan

Location

Investigational Site Number 392037

Kawachi-Nagano-Shi, Japan

Location

Investigational Site Number 392093

Kawagoe-Shi, Japan

Location

Investigational Site Number 392099

Kawasaki-Shi, Japan

Location

Investigational Site Number 392016

Kirishima-Shi, Japan

Location

Investigational Site Number 392013

Kitakyushu-Shi, Japan

Location

Investigational Site Number 392024

Kitakyushu-Shi, Japan

Location

Investigational Site Number 392045

Kitakyushu-Shi, Japan

Location

Investigational Site Number 392063

Kiyose-Shi, Japan

Location

Investigational Site Number 392051

Kobe, Japan

Location

Investigational Site Number 392097

Kochi, Japan

Location

Investigational Site Number 392040

Koushi-Shi, Japan

Location

Investigational Site Number 392069

Kumamoto, Japan

Location

Investigational Site Number 392089

Kurashiki-Shi, Japan

Location

Investigational Site Number 392065

Kushiro, Japan

Location

Investigational Site Number 392026

Matsuyama, Japan

Location

Investigational Site Number 392081

Matsuyama, Japan

Location

Investigational Site Number 392094

Matsuyama, Japan

Location

Investigational Site Number 392042

Meguro-Ku, Japan

Location

Investigational Site Number 392082

Meguro-Ku, Japan

Location

Investigational Site Number 392012

Mito, Japan

Location

Investigational Site Number 392034

Miyagi-Gun, Japan

Location

Investigational Site Number 392053

Morioka, Japan

Location

Investigational Site Number 392032

Nagano, Japan

Location

Investigational Site Number 392064

Nagasaki, Japan

Location

Investigational Site Number 392043

Nagoya, Japan

Location

Investigational Site Number 392056

Nagoya, Japan

Location

Investigational Site Number 392076

Nagoya, Japan

Location

Investigational Site Number 392080

Nagoya, Japan

Location

Investigational Site Number 392031

Nakano, Japan

Location

Investigational Site Number 392046

Narashino-Shi, Japan

Location

Investigational Site Number 392067

Narashino-Shi, Japan

Location

Investigational Site Number 392044

Nishinomiya-Shi, Japan

Location

Investigational Site Number 392062

Okayama, Japan

Location

Investigational Site Number 392008

Omura-Shi, Japan

Location

Investigational Site Number 392057

Osaka, Japan

Location

Investigational Site Number 392060

Osaka, Japan

Location

Investigational Site Number 392061

Osaka, Japan

Location

Investigational Site Number 392096

Osaka, Japan

Location

Investigational Site Number 392027

Osaki-Shi, Japan

Location

Investigational Site Number 392059

Ōita, Japan

Location

Investigational Site Number 392049

Sagamihara-Shi, Japan

Location

Investigational Site Number 392072

Saitama-Shi, Japan

Location

Investigational Site Number 392075

Sakaishi, Japan

Location

Investigational Site Number 392014

Sapporo, Japan

Location

Investigational Site Number 392068

Sapporo, Japan

Location

Investigational Site Number 392073

Sapporo, Japan

Location

Investigational Site Number 392006

Sasebo-Shi, Japan

Location

Investigational Site Number 392021

Sendai, Japan

Location

Investigational Site Number 392022

Sendai, Japan

Location

Investigational Site Number 392033

Sendai, Japan

Location

Investigational Site Number 392071

Sendai, Japan

Location

Investigational Site Number 392100

Sendai, Japan

Location

Investigational Site Number 392029

Shizuoka, Japan

Location

Investigational Site Number 392025

Sumida-Ku, Japan

Location

Investigational Site Number 392092

Sumida-Ku, Japan

Location

Investigational Site Number 392023

Takaoka-Shi, Japan

Location

Investigational Site Number 392095

Takarazuka-Shi, Japan

Location

Investigational Site Number 392020

Takasaki-Shi, Japan

Location

Investigational Site Number 392088

Takatsuki-Shi, Japan

Location

Investigational Site Number 392018

Tokorozawa-Shi, Japan

Location

Investigational Site Number 392003

Tomakomai-Shi, Japan

Location

Investigational Site Number 392005

Tomakomai-Shi, Japan

Location

Investigational Site Number 392077

Tonami-Shi, Japan

Location

Investigational Site Number 392052

Toshima-Ku, Japan

Location

Investigational Site Number 392058

Toyama, Japan

Location

Investigational Site Number 392055

Toyonaka-Shi, Japan

Location

Investigational Site Number 392074

Urasoe-Shi, Japan

Location

Investigational Site Number 392079

Urayasu-Shi, Japan

Location

Investigational Site Number 392048

Yokohama, Japan

Location

Investigational Site Number 392090

Yokohama, Japan

Location

Investigational Site Number 392101

Yokohama, Japan

Location

Related Publications (2)

• Tanaka Y, Takahashi T, Van Hoogstraten H, Praestgaard A, Kato N, Kameda H. Haemoglobin changes and disease activity in Japanese patients with rheumatoid arthritis treated with sarilumab. Clin Exp Rheumatol. 2023 May;41(5):1129-1139. doi: 10.55563/clinexprheumatol/jq9u8f. Epub 2022 Oct 28.

  PMID: 36305354 DERIVED

• Tanaka Y, Wada K, Takahashi Y, Hagino O, van Hoogstraten H, Graham NMH, Kameda H. Sarilumab plus methotrexate in patients with active rheumatoid arthritis and inadequate response to methotrexate: results of a randomized, placebo-controlled phase III trial in Japan. Arthritis Res Ther. 2019 Mar 20;21(1):79. doi: 10.1186/s13075-019-1856-4.

  PMID: 30894208 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

sarilumab; Methotrexate; Folic Acid

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

Study Officials

• Clinical Sciences & Operations

  Sanofi

  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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2014
• First Posted: November 19, 2014
• Study Start: November 1, 2014
• Primary Completion: October 1, 2016
• Study Completion: October 1, 2016
• Last Updated: January 30, 2018
• Results First Posted: January 30, 2018

Record last verified: 2018-01

Locations

JP (96)