A study to evaluate SAR441566 efficacy and safety in adults with rheumatoid arthritis

JRCT ID: jRCT2041230128

Registered date:11/01/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Rheumatoid arthritis
• Date of first enrollment: 15/02/2024
• Target sample size: 240
• Countries of recruitment: Canada,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

Drug: SAR441566
Pharmaceutical form: Tablet, Route of administration: Oral
Drug: Placebo
Pharmaceutical form: Tablet, Route of administration: Oral

Arm description:
- Experimental: SAR441566 dose regimen A
Participant will receive dose regimen A of SAR441566 for 12 weeks
- Experimental: SAR441566 dose regimen B
Participant will receive dose regimen B of SAR441566 for 12 weeks
- Experimental: SAR441566 dose regimen C
Participant will receive dose regimen C of SAR441566 for 12 weeks
- Experimental: SAR441566 dose regimen D
Participant will receive dose regimen D of SAR441566 for 12 weeks
- Placebo Comparator: Placebo
Participant will receive SAR441566-matching placebo for 12 weeks

Outcome(s)

Primary Outcome

1. Proportion of participants achieving at least 20% improvement from baseline in the American College of Rheumatology (ACR) score at week 12
[Time frame: Baseline to 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 (visual analogue scale [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 (erythrocyte sedimentation rate [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.

Secondary Outcome

1. Change from baseline in Disease activity score - CRP (DAS28-CRP) at Week 12
[Time frame: Baseline to 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 global health (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.
2. Pproportion of participants achieving at least 50% improvement from baseline in the ACR score at Week 12
[Time frame: Baseline to 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
3. Number of participants with Treatment-Emergent Adverse Events (TEAEs), serious AEs (SAEs), and AEs of special interest (AESIs)
[Time frame: Baseline to week 14]
Incidence of TEAEs, SAEs, and AESIs
4. Plasma pre-dose concentrations of SAR441566
[Time frame: Week 2 to week 12]
5. Plasma post-dose concentrations of SAR441566
[Time frame: Week 0 to week 12]

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

- Diagnosis of adult-onset rheumatoid arthritis (RA) classified by American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (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 (CRP) > 5 mg/L
- Continuous treatment with methotrexate (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).
- Body mass index (BMI) within the range [18 - 35] kg/m^2 (inclusive)

Exclude criteria

Participants are excluded from the study if any of the following criteria apply:
- 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, intramuscular (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 Day 1. Infections(s) requiring oral anti-infectives (antibiotics, antivirals, antifungals, antihelminthics) within 14 days prior to Day 1.
- 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 (New York Heart Association [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 Janus Kinase [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

Related Information

• Primary Sponsor: Tanaka Tomoyuki
• Secondary ID(s): NCT06073093,2023-503910-60-00