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.

Study Overview

• Status: Active, not recruiting
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: FBL-MTX

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• Portugal
  • Aveiro, Portugal, 3814-501
    • Unidade Local de Saúde da Região de Aveiro, EPE
  • Braga, Portugal, 4710-243
    • Unidade Local de Saúde de Braga, EPE, Centro Clínico Académico de Braga (2CA-Braga)
  • Guarda, Portugal, 6300-858
    • Unidade Local de Saúde da Guarda, EPE
  • Guimarães, Portugal, 4835-044
    • Unidade Local de Saúde do Alto Ave, EPE
  • Leiria, Portugal, 2410-197
    • Unidade Local de Saúde da Região de Leiria, EPE
  • Ponte de Lima, Portugal, 4990-041
    • Unidade Local de Saúde do Alto Minho, EPE
  • Porto, Portugal, 4200-319
    • Unidade Local de Saúde de São João, EPE
  • Vila Nova de Gaia, Portugal, 4434-502
    • Unidade Local de Saúde de Gaia e Espinho, EPE

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: FBL-MTX; 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.

Drug: FBL-MTX; Patients will be administered an initial dose of FBL-MTX by subcutaneous route. Subsequent doses will be titrated according to clinical response. Maximum dosage will be 2.5 mg, every 2 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in Disease Activity Score (DAS) for 28-joint count using C-reactive protein (DAS28-CRP) at Week 14	The DAS28-CRP is a combined index for measuring disease activity in Rheumatoid Arthritis. The components of the DAS28-CRP assessment include: 28 tender and swollen joint counts, CRP, and Patient's Global Assessment of Disease Activity, using a visual analogue scale (VAS): DAS28-CRP = 0.56*sqrt(28*Tender Joint Count) + 0.28*sqrt(28*Swollen joint count) + 0.36*ln(C-Reactive protein+1) + 0.014* global visual analogue scale + 0.96; Note: The 28 joints examined and assessed as tender or not tender for TJC and as swollen or not swollen for SJC include 14 joints on each side of the participant's body: 2 shoulders, 2 elbows, 2 wrists, 10 metacarpophalangeal joints, 2 interphalangeal joints of the thumb, 8 proximal interphalangeal joints, and 2 knees. Higher scores mean a worse outcome.	From screening up to week 14.
Change from baseline in DAS28-CRP at Weeks 4, 8, and 12.	The DAS28-CRP is a combined index for measuring disease activity in Rheumatoid Arthritis. The components of the DAS28-CRP assessment include: 28 tender and swollen joint counts, CRP, and Patient's Global Assessment of Disease Activity, using a visual analogue scale (VAS): DAS28-CRP = 0.56*sqrt(28*Tender Joint Count) + 0.28*sqrt(28*Swollen joint count) + 0.36*ln(C-Reactive protein+1) + 0.014* global visual analogue scale + 0.96; Note: The 28 joints examined and assessed as tender or not tender for TJC and as swollen or not swollen for SJC include 14 joints on each side of the participant's body: 2 shoulders, 2 elbows, 2 wrists, 10 metacarpophalangeal joints, 2 interphalangeal joints of the thumb, 8 proximal interphalangeal joints, and 2 knees. Higher scores mean a worse outcome.	From screening up to weeks 4, 8 and 12.
Number of subjects who achieve remission (DAS28-CRP <2.6) at Weeks 4, 8, 12, and 14.	The DAS28-CRP is a combined index for measuring disease activity in Rheumatoid Arthritis. The components of the DAS28-CRP assessment include: 28 tender and swollen joint counts, CRP, and Patient's Global Assessment of Disease Activity, using a visual analogue scale (VAS): DAS28-CRP = 0.56*sqrt(28*Tender Joint Count) + 0.28*sqrt(28*Swollen joint count) + 0.36*ln(C-Reactive protein+1) + 0.014* global visual analogue scale + 0.96; Note: The 28 joints examined and assessed as tender or not tender for TJC and as swollen or not swollen for SJC include 14 joints on each side of the participant's body: 2 shoulders, 2 elbows, 2 wrists, 10 metacarpophalangeal joints, 2 interphalangeal joints of the thumb, 8 proximal interphalangeal joints, and 2 knees. Higher scores mean a worse outcome.	From screening up to weeks 4, 8, 12 and 14.
Number of subjects who achieve low disease activity (DAS28-CRP <3.2) at Weeks 4, 8, 12, and 14.		From screening up to weeks 4, 8, 12 and 14.
Number of subjects who achieve American College of Rheumatology (ACR) 20% (ACR20) response at Weeks 4, 8, 12, and 14.		From screening up to weeks 4, 8, 12 and 14.
Number of subjects who achieve ACR50 response at Weeks 4, 8, 12, and 14.		From screening up to weeks 4, 8, 12 and 14.
Number of subjects who achieve ACR70 response at Weeks 4, 8, 12, and 14.		From screening up to weeks 4, 8, 12 and 14.
Change from baseline in Clinical Disease Activity Index (CDAI) at Weeks 4, 8, 12, and 14.		From screening up to weeks 4, 8, 12 and 14.
Change from baseline in Simplified Disease Activity Index (SDAI) at Weeks 4, 8, 12, and 14.		From screening up to weeks 4, 8, 12 and 14.
Change from baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) score at Weeks 4, 8, 12, and 14.		From screening up to weeks 4, 8, 12 and 14.
Change from baseline in Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) at Week 14.		From screening up to Week 14.

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of TEAEs and SAEs. Clinically relevant abnormalities in vital signs, 12-lead ECG, and laboratory parameters will be reported as AEs.	From date of screening until the date of the last post-study follow-up visit.

Collaborators and Investigators

• Sponsor: SOLFARCOS - Pharmaceutical and Cosmetic Solutions Ltd
• Investigators: Principal Investigator: José Costa, MD, Unidade Local de Saúde do Alto Minho, EPE

Study record dates

Study Major Dates

• Study Start (Actual): July 24, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: August 8, 2024
• First Submitted That Met QC Criteria: August 20, 2024
• First Posted (Actual): August 21, 2024

Study Record Updates

• Last Update Posted (Actual): June 11, 2026
• Last Update Submitted That Met QC Criteria: June 9, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin and Connective Tissue Diseases; Arthritis, Rheumatoid
• Other Study ID Numbers: FBL-MTX-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No