Clinical trial NCT06073093: A Study to Evaluate SAR441566 Efficacy and Safety in Adults With Rheumatoid Arthritis
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2023-10-10
Enrollment: 264
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 (4 to 6 weeks) 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.

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

Eligibility criteria: 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 ≥ 4 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) 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
* 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 (other than RA) 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 3 months prior to screening or plan to receive one during the trial including at least 3 months after the last dose of study drug
* 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

The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.

Primary outcomes:
measure: Proportion of participants achieving at least 20% improvement from baseline in the American College of Rheumatology (ACR) score at week 12
timeFrame: Baseline to Week 12
Secondary outcomes:
measure: Change from baseline in Disease activity score - C-reactive protein (DAS-28 CRP) at week 12
timeFrame: Baseline to Week 12
measure: Proportion of participants achieving at least 50% improvement from baseline in the ACR score at week 12
timeFrame: Baseline to week 12
measure: Number of participants with Treatment-Emergent Adverse Events (TEAEs), serious AEs (SAEs), and AEs of special interest (AESIs)
timeFrame: Baseline to week 14
measure: Plasma pre-dose concentrations of SAR441566
timeFrame: Week 2 to week 12
measure: Plasma post-dose concentrations of SAR441566
timeFrame: Week 0 to week 12
Other outcomes:
Locations:
city: Northridge
country: United States
facility: Amicis Research Center - Northridge - Nordhoff Street- Site Number : 8400023
state: California
city: Upland
country: United States
facility: Inland Rheumatology & Osteoporosis Medical Group- Site Number : 8400004
state: California
city: Jacksonville
country: United States
facility: UF Health Deerwood Park- Site Number : 8400020
state: Florida
city: Margate
country: United States
facility: Life Clinical Trials- Site Number : 8400028
state: Florida
city: Miami
country: United States
facility: Future Care Solution - Miami- Site Number : 8400019
state: Florida
city: Miramar
country: United States
facility: Innovia Research Center, Inc- Site Number : 8400026
state: Florida
city: Plantation
country: United States
facility: Integral Rheumatology and Immunology Specialists- Site Number : 8400010
state: Florida
city: Tampa
country: United States
facility: Clinical Research of West Florida - Tampa - North Howard Avenue- Site Number : 8400017
state: Florida
city: Santa Fe
country: United States
facility: Inspire Santa Fe Medical Group- Site Number : 8400029
state: New Mexico
city: Charlotte
country: United States
facility: Arthritis and Osteoporosis Consultants of the Carolinas- Site Number : 8400012
state: North Carolina
city: Statesville
country: United States
facility: Carolina Specialty Care- Site Number : 8400007
state: North Carolina
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research- Site Number : 8400002
state: Pennsylvania
city: Summerville
country: United States
facility: Low Country Rheumatology- Site Number : 8400018
state: South Carolina
city: Rapid City
country: United States
facility: American Indian Clinical Trials Research Network - Rapid City- Site Number : 8400022
state: South Dakota
city: Houston
country: United States
facility: Prolato Clinical Research Center- Site Number : 8400021
state: Texas
city: Irving
country: United States
facility: AARA Clinical Research - Lone Star Arthritis & Rheumatology Associates - Irving- Site Number : 8400031
state: Texas
city: Richmond
country: United States
facility: Perceptive Pharma Research- Site Number : 8400009
state: Texas
city: Berazategui
country: Argentina
facility: Investigational Site Number : 0320005
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320004
state: Ciudad De Buenos Aires
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320001
state: Ciudad De Buenos Aires
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320003
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320007
city: Mar Del Plata
country: Argentina
facility: Investigational Site Number : 0320006
city: San Miguel de Tucuman
country: Argentina
facility: Investigational Site Number : 0320002
city: San Miguel de Tucumán
country: Argentina
facility: Investigational Site Number : 0320002
city: Juiz de Fora
country: Brazil
facility: Centro Mineiro de Pesquisa- Site Number : 0760003
state: Minas Gerais
city: Curitiba
country: Brazil
facility: Centro de Estudos em Terapias Inovadoras- Site Number : 0760004
state: Paraná
city: Rio de Janeiro
country: Brazil
facility: Hospital São Lucas Copacabana- Site Number : 0760007
city: Rio de Janeiro
country: Brazil
facility: CCBR / IBPClin - Instituto Brasil de Pesquisa Clínica- Site Number : 0760005
city: São Paulo
country: Brazil
facility: Centro Paulista de Investigaçăo Clínica - CEPIC- Site Number : 0760001
city: Calgary
country: Canada
facility: Investigational Site Number : 1240006
state: Alberta
city: Brampton
country: Canada
facility: Investigational Site Number : 1240001
state: Ontario
city: Windsor
country: Canada
facility: Investigational Site Number : 1240004
state: Ontario
city: Sherbrooke
country: Canada
facility: Investigational Site Number : 1240002
state: Quebec
city: La Serena
country: Chile
facility: Investigational Site Number : 1520001
state: Coquimbo
city: Osorno
country: Chile
facility: Investigational Site Number : 1520003
state: Los Lagos
city: Valdivia
country: Chile
facility: Investigational Site Number : 1520005
state: Los Ríos
city: Talca
country: Chile
facility: Investigational Site Number : 1520002
state: Maule
city: Santiago
country: Chile
facility: Investigational Site Number : 1520004
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number : 1520006
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number : 1520008
state: Reg Metropolitana De Santiago
city: Viña Del Mar
country: Chile
facility: Investigational Site Number : 1520007
state: Valparaíso
city: Santiago
country: Chile
facility: Investigational Site Number : 1520009
city: Chengdu
country: China
facility: Investigational Site Number : 1560004
city: Hefei
country: China
facility: Investigational Site Number : 1560003
city: Shanghai
country: China
facility: Investigational Site Number : 1560001
city: Brno
country: Czechia
facility: Investigational Site Number : 2030006
city: Ostrava
country: Czechia
facility: Investigational Site Number : 2030002
city: Pardubice
country: Czechia
facility: Investigational Site Number : 2030008
city: Prague
country: Czechia
facility: Investigational Site Number : 2030001
city: Uherské Hradiště
country: Czechia
facility: Investigational Site Number : 2030003
city: Tbilisi
country: Georgia
facility: Investigational Site Number : 2680001
city: Berlin
country: Germany
facility: Investigational Site Number : 2760002
city: Hamburg
country: Germany
facility: Investigational Site Number : 2760001
city: Ratingen
country: Germany
facility: Investigational Site Number : 2760003
city: Athens
country: Greece
facility: Investigational Site Number : 3000001
city: Heraklion
country: Greece
facility: Investigational Site Number : 3000002
city: Thessaloniki
country: Greece
facility: Investigational Site Number : 3000003
city: Ahmedabad
country: India
facility: Investigational Site Number : 3560006
city: Bengaluru
country: India
facility: Investigational Site Number : 3560002
city: Chennai
country: India
facility: Investigational Site Number : 3560001
city: Hyderabad
country: India
facility: Investigational Site Number : 3560010
city: Kolkata
country: India
facility: Investigational Site Number : 3560007
city: Nashik
country: India
facility: Investigational Site Number : 3560011
city: Surat
country: India
facility: Investigational Site Number : 3560005
city: Nagoya
country: Japan
facility: Investigational Site Number : 3920005
state: Aichi
city: Kamogawa
country: Japan
facility: Investigational Site Number : 3920007
state: Chiba
city: Sapporo
country: Japan
facility: Investigational Site Number : 3920006
state: Hokkaido
city: Sapporo
country: Japan
facility: Investigational Site Number : 3920009
state: Hokkaido
city: Kawachinagano
country: Japan
facility: Investigational Site Number : 3920004
state: Osaka
city: Toyonaka
country: Japan
facility: Investigational Site Number : 3920003
state: Osaka
city: Fuchu
country: Japan
facility: Investigational Site Number : 3920002
state: Tokyo
city: Nagasaki
country: Japan
facility: Investigational Site Number : 3920008
city: Tokorozawa
country: Japan
facility: Investigational Site Number : 3920011
city: Toyota
country: Japan
facility: Investigational Site Number : 3920001
city: Vacoas-phoenix
country: Mauritius
facility: Investigational Site Number : 4800001
city: Mexico City
country: Mexico
facility: Investigational Site Number : 4840002
state: Ciudad De Mexico
city: Chihuahua
country: Mexico
facility: Investigational Site Number : 4840001
city: Mérida
country: Mexico
facility: Investigational Site Number : 4840003
city: Lublin
country: Poland
facility: Investigational Site Number : 6160001
state: Lubuskie
city: Lublin
country: Poland
facility: Investigational Site Number : 6160002
state: Lubuskie
city: Bialystok
country: Poland
facility: Investigational Site Number : 6160003
state: Podlaskie
city: Bytom
country: Poland
facility: Investigational Site Number : 6160005
state: Slaskie
city: Poznan
country: Poland
facility: Investigational Site Number : 6160004
state: Wielkopolskie
city: Grodzisk Mazowiecki
country: Poland
facility: Investigational Site Number : 6160006
city: San Juan
country: Puerto Rico
facility: Caribbean Medical Research Center- Site Number : 8400027
city: Nové Mesto Nad Váhom
country: Slovakia
facility: Investigational Site Number : 7030003
city: Piešťany
country: Slovakia
facility: Investigational Site Number : 7030001
city: Cape Town
country: South Africa
facility: Investigational Site Number : 7100002
city: Cape Town
country: South Africa
facility: Investigational Site Number : 7100003
city: Pretoria
country: South Africa
facility: Investigational Site Number : 7100001
city: Pretoria
country: South Africa
facility: Investigational Site Number : 7100005
city: Pretoria
country: South Africa
facility: Investigational Site Number : 7100004
city: Stellenbosch
country: South Africa
facility: Investigational Site Number : 7100007
city: A Coruña
country: Spain
facility: Investigational Site Number : 7240001
state: A Coruña [La Coruña]
city: Santiago de Compostela
country: Spain
facility: Investigational Site Number : 7240002
state: A Coruña [La Coruña]
city: Santiago de Compostela
country: Spain
facility: Investigational Site Number : 7240006
state: A Coruña [La Coruña]
city: Seville
country: Spain
facility: Investigational Site Number : 7240005
state: Andalucia
city: Sabadell
country: Spain
facility: Investigational Site Number : 7240004
state: Castilla Y León
city: Chiclana de La Frontera
country: Spain
facility: Investigational Site Number : 7240008
city: Madrid
country: Spain
facility: Investigational Site Number : 7240007
city: Málaga
country: Spain
facility: Investigational Site Number : 7240003
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: