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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sanofi-Aventis Recherche & Developpement

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

5 Mar 2024 → 3 Jul 2025

Decision date (initial)

2024-02-06

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Sanofi-Aventis Research & Development

External identifiers

EU CT number

2023-503910-60-00

WHO UTN

U1111-1288-8641

ClinicalTrials.gov

NCT06073093

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacodynamic, Pharmacokinetic, Pharmacogenomic, Safety

To demonstrate that SAR441566, a small molecule specific inhibitor of TNFR1 signaling compared to placebo, plus methotrexate (MTX), is effective in the treatment of moderate-to-severe rheumatoid arthritis (RA) with regards to American College of Rheumatology 20 (ACR20)

Secondary objectives 3

1. To assess the efficacy of SAR441566, with respect to placebo, plus MTX, on change from baseline to week 12 in Disease Activity Score 28-C-reactive Protein (DAS-28-CRP) and response to ACR50 in the treatment of RA
2. To evaluate the safety and tolerability of SAR441566
3. To assess pharmacokinetics (PK) of SAR441566 in participants with RA

Conditions and MedDRA coding

Rheumatoid arthritis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. 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
2. Moderate-to-severely active RA, defined as: • persistently active disease >= 6 tender and >= 6 swollen joints • high sensitivity C-reactive protein ≥4 mg/L
3. 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).
4. Inadequate clinical response to MTX at a dose of 10-25 mg/week after proper dose escalation according to local standards .
5. BMI within the range [18 – 35] kg/m2 (inclusive)

Exclusion criteria 19

1. 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.
2. Planned surgery during the treatment period.
3. 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).
4. 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
5. Any non-live vaccine (eg, COVID-19) within 14 days prior to randomization or plan to receive one during the trial.
6. Participant with personal or family history of long QT syndrome.
7. 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.
8. Previous or current use of biologic therapy or targeted synthetic disease modifying anti-rheumatic drugs (tsDMARD - such as JAK inhibitors) for RA.
9. 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.
10. Use of parenteral glucocorticoids or intra-articular glucocorticoids within 4 weeks prior to screening.
11. Initiation or change in dose for nonsteroidal anti-inflammatory drugs (NSAIDs) within 1 week prior to screening.
12. Any condition (other than RA) requiring oral, intravenous, IM, or intra-articular glucocorticoid therapy.
13. Uncontrolled polymyalgia rheumatica or fibromyalgia.
14. 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.
15. 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.
16. 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.
17. History of solid organ transplant.
18. History of alcohol or drug abuse within the past 2 years.
19. 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).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of participants achieving at least 20% improvement from baseline in the American College of Rheumatology (ACR) score at week 12

Secondary endpoints 5

1. Change from baseline in Disease activity score – C-reactive protein (DAS-28 CRP) at week 12
2. Proportion of participants achieving at least 50% improvement from baseline in the ACR score at week 12
3. Number of participants with Treatment-Emergent Adverse Events (TEAEs), serious AEs (SAEs), and AEs of special interest (AESIs)
4. Plasma pre-dose concentrations of SAR441566
5. Plasma post-dose concentrations of SAR441566

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sanofi-Aventis Recherche & Developpement

Sponsor organisation

Sanofi-Aventis Recherche & Developpement

Address

82 Avenue Raspail

City

Gentilly

Postcode

94250

Country

France

Scientific contact point

Organisation

Sanofi-Aventis Research & Development

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Sanofi-Aventis Research & Development

Contact name

Clinical Sciences and Operations

Third parties 12

Locations

6 EU/EEA countries · 30 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 103 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications