Study to Investigate the Efficacy, Safety, and Tolerability of FBL-MTX in Patients With Rheumatoid Arthritis

Phase IIa Proof-of-Concept Study, With Dose-Titration Based on Treat-to-Target Strategy, to Investigate the Efficacy, Safety, and Tolerability of Subcutaneous Injection of Folate-based Liposomes Encapsulating Methotrexate (FBL-MTX) in Disease-modifying Antirheumatic Drugs (DMARD)-naïve Patients With Moderate-to-Severe Active Rheumatoid Arthritis and in Patients With an Inadequate Response or Intolerance to Oral MTX.

The goal of this clinical trial is to evaluate the efficacy of FBL-MTX administered by subcutaneous route in Rheumatoid Arthritis patients.

Participants will be screened within 28 days prior to treatment period, to confirm that they meet the selection criteria for the study.

Treatment period: The treatment period will consist of eight sequential study visits, separated by a 2-week interval.

• DMARD-naïve Patients: Patients will be administered an initial dose of FBL-MTX of 1 mg, by SC route. Subsequent doses will be titrated according to clinical response at intervals of 4 weeks, for 12 weeks. Maximum dosage will be 2.5 mg, every 2 weeks.
• Patients with an Inadequate Response or Intolerance to Oral MTX: Patients will be administered an initial dose of FBL-MTX 2.5 mg, by SC route. Subsequent doses will be titrated according to clinical response at intervals of 4 weeks, for 12 weeks. Maximum dosage will be 2.5 mg, every two weeks.

The Sponsor is developing folate-based liposomes encapsulating methotrexate (FBL-MTX) as a putative therapy for RA, by intravenous (IV) or subcutaneous (SC) administration.

Considering the presented non-clinical and clinical data for FBL-MTX and that SC administration is the most adequate route for patient self-administration, the Sponsor intends to proceed the clinical development of FBL-MTX with the objective of providing a more patient-friendly product with at least the same efficacy.

This proof-of-concept study intends to demonstrate the plausibility of FBL-MTX SC administration in patients through the exploratory evaluation of SC FBL-MTX efficacy in patients with moderate-to-severe active RA, and collection data on its safety and tolerability.

Inclusion Criteria:

• Male or non-pregnant female subjects with moderate-to-severe active RA, age ≥ 18 years, Body Mass Index > 35 kg/m2.
• Diagnosis of RA according to the 2010 classification criteria of the American College of Rheumatology/ European Alliance of Associations for Rheumatology, formerly known as European League Against Rheumatism, (ACR/EULAR), with a Total Score ≥ 6/10.
• At least moderately active disease, as defined by DAS28-CRP >3.2 at Screening and Baseline, including:
• Tender joint count (TJC) ≥ 4
• Swollen joint count (SJC) ≥ 4
• C Reactive protein (CRP) ≥ 5 mg/L
• Documented history of positive RA factor and/or cyclic citrullinated peptide antibody test.
• Chest X-ray performed in the previous 3 months not suggestive of tuberculosis.
• If under nonsteroidal anti-inflammatory drugs (NSAIDs), must be able to be on a stable regimen from at least 2 weeks before baseline up to end-of-study.
• If under an oral corticosteroid (≤ 10 mg per day of prednisone or equivalent), must be able to be on a stable regimen from at least 4 weeks before baseline up to EoS.
• Eligible to start treatment with an immunomodulator.
• No evidence of clinically significant active infection.

Exclusion Criteria:

• Positive Interferon-Gamma Release Assay (IGRA) test result.
• Creatinine clearance < 60 mL/min.