A Study to Evaluate SAR441566 Efficacy and Safety in Adults With Rheumatoid Arthritis (SPECIFI-RA)

Sanofi

Status and phase: Enrolling; Phase 2

Conditions: Rheumatoid Arthritis

Treatments: Drug: SAR441566; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT06073093

DRI17821

U1111-1288-8641 (Registry Identifier)

2023-503910-60-00 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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

Enrollment: 240 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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240 participants in 5 patient groups, including a placebo group

SAR441566 dose regimen A

Experimental group

Description:

Participant will receive dose regimen A of SAR441566 for 12 weeks

Treatment:

Drug: SAR441566

SAR441566 dose regimen B

Experimental group

Description:

Participant will receive dose regimen B of SAR441566 for 12 weeks

Treatment:

Drug: SAR441566

SAR441566 dose regimen C

Experimental group

Description:

Participant will receive dose regimen C of SAR441566 for 12 weeks

Treatment:

Drug: SAR441566

SAR441566 dose regimen D

Experimental group

Description:

Participant will receive dose regimen D of SAR441566 for 12 weeks

Treatment:

Drug: SAR441566

Placebo

Placebo Comparator group

Description:

Participant will receive SAR441566-matching placebo for 12 weeks

Treatment:

Drug: Placebo