A Study to Evaluate SAR441566 Efficacy and Safety in Adults With Rheumatoid Arthritis

Rheumatoid Arthritis Clinical Trial

— SPECIFI-RA  

Official title:

A Phase 2 Randomized, Double-blind, Placebo-controlled, Dose-ranging, Efficacy and Safety Study of SAR441566 Plus Methotrexate in Adults With ModeratetoSevere Rheumatoid Arthritis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06073093
• Other study ID #: DRI17821
• Secondary ID: 2023-503910-60U1
• Status: Recruiting
• Phase: Phase 2
• Start date: November 7, 2023
• Est. completion date: August 8, 2025

Study information

• Verified date: May 2024
• Source: Sanofi
• Contact: Trial transparency email recommended (Toll free for US & Canada)
• Phone: 800-633-1610
• Email: contact-us[@]sanofi.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a parallel group, Phase 2, randomized, double-blind, placebo controlled, 5-arm, international, multicenter, 12-week proof of concept, dose finding study. It is designed to assess efficacy and safety of treatment with SAR441566 for 12 weeks. It will be conducted in male and female adult participants with moderate-to-severe rheumatoid arthritis (RA) not adequately controlled on methotrexate (MTX) and biologic/targeted synthetic disease modifying anti-rheumatic drug (DMARD) naive. Study treatment includes investigational medicinal product (IMP: SAR441566 or placebo) added-on to a background therapy of MTX. Study details include a run-in period (6 weeks ± 3 days) before randomization to determine eligibility, a treatment period (12 weeks ± 3 days) and a post-treatment period (safety follow-up) (2 weeks ± 3 days). The total number of scheduled study visits will be 8.

Description:

The overall study duration for each participant will be approximately up to 149 days.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: August 8, 2025
• Est. primary completion date: June 13, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis of adult-onset RA classified by ACR/EULAR 2010 revised classification criteria for RA of at least 3 months duration, with the onset of signs and symptoms of RA of at least 6 months duration
• Moderate-to-severely active RA, defined as:
• persistently active disease >= 6 tender and >= 6 swollen joints
• high sensitivity C-reactive protein > 5 mg/L
• Continuous treatment with MTX for at least 12 consecutive weeks prior to randomization and with stable dose/means of administration at least 6 weeks prior to the screening visit
• MTX - 10 to 25 mg/week (or per local labeling requirements for the treatment of RA if the dose range differs, eg, for Japan, a stable dose of MTX is 6 to 16 mg/week) and folic/folinic acid (as part of MTX regimen)
• Inadequate clinical response to MTX at a dose of 10-25 mg/week after proper dose escalation according to local standards (eg, for Japan, a stable dose of MTX is 6 to 16 mg/week)
• BMI within the range [18 - 35] kg/m^2 (inclusive)

Exclusion Criteria:

• Immunologic disorder other than RA, with the exception of secondary Sjogren's syndrome associated with RA, and medically controlled diabetes or thyroid disorder as per Investigator's judgement
• Any condition requiring oral, intravenous, IM, or intra-articular glucocorticoid therapy
• Uncontrolled polymyalgia rheumatica or fibromyalgia
• History of recurrent or recent serious infection (eg, pneumonia, septicemia) or infection(s) requiring hospitalization or treatment with IV anti-infectives (antibiotics, antivirals, antifungals, antihelminthics) within 30 days prior to D1. Infections(s) requiring oral anti-infectives (antibiotics, antivirals, antifungals, antihelminthics) within 14 days prior to D1
• Known history of or suspected significant current immunosuppression, including history of invasive opportunistic or helminthic infections despite infection resolution or otherwise recurrent infections of abnormal frequency or prolonged duration
• History of moderate-to-severe congestive heart failure (NYHA Class III or IV), recent cerebrovascular accident, or any other condition in the opinion of the Investigator that would put the participant at risk by participation in the protocol
• History of solid organ transplant
• History of alcohol or drug abuse within the past 2 years
• History of diagnosis of demyelinating disease such as but not limited to:
• Multiple Sclerosis
• Acute Disseminated Encephalomyelitis
• Balo's Disease (Concentric Sclerosis)
• Charcot-Marie-Tooth Disease
• Guillain-Barre Syndrome
• human T-lymphotropic virus 1 Associated Myelopathy
• Neuromyelitis Optica (Devic's Disease)
• Planned surgery during the treatment period
• Participants who are Steinbrocker class IV functional capacity (incapacitated, largely or wholly bed-ridden or confined to a wheelchair, with little or no self-care)
• Vaccination with live or live-attenuated virus vaccine within 6 weeks prior to randomization or plan to receive one during the trial
• Any non-live vaccine (eg, COVID-19) within 14 days prior to randomization or plan to receive one during the trial
• Participant with personal or family history of long QT syndrome
• Active malignancy, lymphoproliferative disease, or malignancy in remission for less than 5 years, except adequately treated (cured) localized carcinoma in situ of the cervix or ductal breast, or squamous cell carcinoma, or basal cell carcinoma of the skin
• Previous or current use of biologic therapy or targeted synthetic disease modifying anti-rheumatic drugs (tsDMARD - such as JAK inhibitors) for RA
• Use of oral glucocorticoid greater than prednisone 10 mg per day or equivalent per day, or a change in dosage within 4 weeks prior to screening. The dose of oral glucocorticoid must remain stable.
• Use of parenteral glucocorticoids or intra-articular glucocorticoids within 4 weeks prior to screening
• Initiation or change in dose for nonsteroidal anti-inflammatory drugs (NSAIDs) within 1 week prior to screening
• Prior use of conventional disease-modifying anti-rheumatic drugs (cDMARDs) other than MTX The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• SAR441566
Tablet
• Placebo
Tablet

Locations

Country	Name	City	State
Argentina	Investigational Site Number : 0320001	Caba	Ciudad De Buenos Aires
Argentina	Investigational Site Number : 0320004	Ciudad de Buenos Aires
Argentina	Investigational Site Number : 0320006	Mar del Plata
Argentina	Investigational Site Number : 0320002	San Miguel de Tucuman
Brazil	CETI - Centro de Estudos em Terapias Inovadoras Site Number : 0760004	Curitiba	Paraná
Canada	Investigational Site Number : 1240001	Brampton	Ontario
Chile	Investigational Site Number : 1520001	La Serena	Coquimbo
Chile	Investigational Site Number : 1520004	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number : 1520006	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number : 1520009	Santiago de Chile
Chile	Investigational Site Number : 1520002	Talca	Maule
Chile	Investigational Site Number : 1520005	Valdivia	Los Ríos
China	Investigational Site Number : 1560001	Shanghai
Czechia	Investigational Site Number : 2030006	Brno-Sever
Czechia	Investigational Site Number : 2030002	Ostrava
Czechia	Investigational Site Number : 2030003	Uherske Hradiste
Georgia	Investigational Site Number : 2680001	Tbilisi
Germany	Investigational Site Number : 2760002	Berlin
Germany	Investigational Site Number : 2760001	Hamburg
Germany	Investigational Site Number : 2760003	Ratingen
Japan	Investigational Site Number : 3920007	Kamogawa-shi	Chiba
Japan	Investigational Site Number : 3920004	Kawachinagano-shi	Osaka
Japan	Investigational Site Number : 3920005	Nagoya-shi	Aichi
Japan	Investigational Site Number : 3920006	Sapporo-shi	Hokkaido
Japan	Investigational Site Number : 3920003	Toyonaka-shi	Osaka
Japan	Investigational Site Number : 3920001	Toyota-shi
Mauritius	Investigational Site Number : 4800001	Quatre Bornes
Poland	Investigational Site Number : 6160003	Bialystok	Podlaskie
Poland	Investigational Site Number : 6160005	Bytom	Slaskie
Poland	Investigational Site Number : 6160006	Grodzisk Mazowiecki
Poland	Investigational Site Number : 6160001	Lublin	Lubuskie
Poland	Investigational Site Number : 6160002	Lublin	Lubuskie
Poland	Investigational Site Number : 6160004	Poznan	Wielkopolskie
Slovakia	Investigational Site Number : 7030001	Piestany
South Africa	Investigational Site Number : 7100002	Cape Town
South Africa	Investigational Site Number : 7100003	Cape Town
South Africa	Investigational Site Number : 7100001	Pretoria
South Africa	Investigational Site Number : 7100004	Pretoria
South Africa	Investigational Site Number : 7100005	Pretoria
Spain	Investigational Site Number : 7240004	Barcelona / Sabadell	Castilla Y León
Spain	Investigational Site Number : 7240001	La Coruña	A Coruña [La Coruña]
Spain	Investigational Site Number : 7240003	Málaga
Spain	Investigational Site Number : 7240002	Santiago de Compostela	A Coruña [La Coruña]
Spain	Investigational Site Number : 7240005	Sevilla	Andalucia
United States	Arthritis and Osteoporosis Consultants of the Carolinas Site Number : 8400012	Charlotte	North Carolina
United States	DJL Clinical Research, PLLC Site Number : 8400007	Charlotte	North Carolina
United States	Altoona Center For Clinical Research Site Number : 8400002	Duncansville	Pennsylvania
United States	Texas Arthritis Center Site Number : 8400015	El Paso	Texas
United States	Future Care Solutions, LLC Site Number : 8400019	Miami	Florida
United States	Trinity Universal Research Associates Site Number : 8400008	Plano	Texas
United States	Iris Rheumatology Site Number : 8400010	Plantation	Florida
United States	Perceptive Pharma Research Site Number : 8400009	Richmond	Texas
United States	Clinical Research of West Florida Site Number : 8400017	Riverview	Florida
United States	Inland Rheumatology Clinical Trials, Inc. Site Number : 8400004	Upland	California
United States	Florida Medical Clinic, LLC Site Number : 8400014	Zephyrhills	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Canada,  Chile,  China,  Czechia,  Georgia,  Germany,  Japan,  Mauritius,  Poland,  Slovakia,  South Africa,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of participants achieving at least 20% improvement from baseline in the American College of Rheumatology (ACR) score at week 12	ACR20 response criteria is a dichotomous composite endpoint indicating the proportion of participants with at least 20 percent improvement in the number of tender and swollen joints, and in three out of the remaining five ACR core-set measures: patient pain (VAS, No pain to Severe Pain), Patient Global Assessment of disease activity (VAS, Very well to Very Poor), physician global assessment of disease activity (VAS, Very good to Very bad), physical functioning assessment (Health Assessment Questionnaire-Disability Index [HAQ-DI]), and acute phase reactants (ESR or CRP mg/dl; in this study CRP will be used). ACR response is scored as a percentage improvement, comparing disease activity at two discrete time points. ACR20 is = 20% improvement.	Baseline to Week 12
Secondary	Change from baseline in Disease activity score - C-reactive protein (DAS-28 CRP) at week 12	The DAS28-CRP is a composite endpoint. DAS28-CRP is comprised of clinical assessment of 28 swollen joint count (SJC)/ tender joint count (TJC), patient assessment of global disease activity and CRP mg/dL. It is a continuous measure allowing for measurement of absolute change in disease burden and percentage improvement.; The DAS28 can be calculated using the following formula: DAS28 = 0.56 x 28TJC + 0.28 x 28SJC + 0.36 x Log(CRP+1) + 0.014 x GH + 0.96 The DAS28 provides a number indicating the current activity of the RA. A DAS28 above 5.1 means high disease activity, whereas a DAS28 below 3.2 indicates low disease activity and a DAS28 below 2.6 means disease remission.	Baseline to Week 12
Secondary	Proportion of participants achieving at least 50% improvement from baseline in the ACR score at week 12	ACR response is scored as a percentage improvement, comparing disease activity at two discrete time points. ACR50 is = 50% improvement. ACR50 responders include ACR20 responders	Baseline to week 12
Secondary	Number of participants with Treatment-Emergent Adverse Events (TEAEs), serious AEs (SAEs), and AEs of special interest (AESIs)	Incidence of TEAEs, SAEs, and AESIs	Baseline to week 14
Secondary	Plasma pre-dose concentrations of SAR441566		Week 2 to week 12
Secondary	Plasma post-dose concentrations of SAR441566		Week 0 to week 12