A Placebo controlled trial in adult patients with active rheumatoid arthritis with inadequate (partial) response to anti-TNF therapy

Phase 1

• Conditions: Active Rheumatoid Arthritis; MedDRA version: 23.1Level: PTClassification code 10039073Term: Rheumatoid arthritisSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders; Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: EUCTR2020-003955-14-DE
• Lead Sponsor: Applied Molecular Transport Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-11-04
• Last Update Posted: 28 March 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

• Female and male patients aged =18 and <75 years old, inclusive at the time of informed consent.
• Body weight of = 45 kilograms (kg) and =100 kg and must have a body mass index (BMI) within the range of 18.5 – 34.9 kg/m2.
• Diagnosed with RA under the 1987 American College of Rheumatology (ACR) or 2010 ACR/European League Against Rheumatism (EULAR) criteria for at least 6 months before.
• Patients must be taking anti-TNF biologic treatment under approved dosage and administration for =12 weeks and < 3 years but only had an inadequate response according to Investigator judgement a) DAS28(CRP) > 4.4 and = 5.1 or b) DAS28(CRP) = 3.2 and = 5.1 plus at least 2/28 swollen and tender joints (except joint surgery).
• History of biologics treatment should be limited to anti-TNF agents among adalimumab, infliximab, golimumab, etanercept, certolizumab (including biosimilars).
• Two or more swollen and tender joints in the Screening Phase (out of 28 joints).

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 12
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 8

Exclusion Criteria

• Any history or complication of an inflammatory arthritic disorder other than RA
• Any history of Inflammatory Bowel Disease (Ulcerative Colitis or Crohn’s disease)
• Meets the ACR 1991 Revised Criteria for the Classification of Global Functional Status in RA Class IV.
• Received IV Immunoglobulin (IV Ig) preparations or blood products within 24 weeks before starting the study treatment.
• Received a live vaccine within 12 weeks before starting the study treatment, or is planning to receive a live vaccine during the study
• Current therapy with any non-MTX synthetic small-molecule DMARD (including but not limited to sulfasalazine, azathioprine, hydroxychloroquine, and/or leflunomide) for at least 1 month prior to the Screening Visit or concomitantly during the trial.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Timepoint(s) of evaluation of this end point: 12 weeks;Main Objective: To assess the safety and tolerability of 12 weeks of daily oral AMT-101 in patients with active RA who have an inadequate response to anti-TNF therapy;Secondary Objective: • To assess the biologic activity of 12 weeks of daily oral AMT-101 by changes in the DAS-28 (CRP), SDAI and CDAI, and ACR 20, 50, 70<br>• To examine the pharmacokinetic and pharmacodynamic effects of AMT-101 <br>• To examine the immunogenicity of AMT-101<br>;Primary end point(s): • Proportion of patients with treatment-emergent adverse events (TEAEs), SAEs, and discontinuation due to TEAEs <br>• Assessment of physical examinations, laboratory parameters, vital signs, and ECGs

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): • Efficacy: Change over time in:<br> - DAS-28(CRP), SDAI and CDAI, ACR 20, 50,70<br> - Proportion of patients with DAS-28(CRP) less than 2.6<br> - Proportion of patients with DAS-28(CRP) less than 3.2<br> - Proportion of patients with Boolean Remission<br> - Change in acute phase reactants (CRP, ESR)<br>• Pharmacokinetics: Change in AMT-101 and Serum IL-10 levels <br>• Pharmacodynamics: Change in Rheumatoid Factor, anti-citrullinated Cyclic Peptide antibody levels<br>• Immunogenicity: Incidence of anti-AMT-101 antibodies ;Timepoint(s) of evaluation of this end point: • Efficacy: at treatment completion and 4 weeks post completion<br>• Pharmacokinetics: baseline, Day 1- at 8 and 24 hrs. and at weeks 2, 4, 8, and 12<br>• Pharmacodynamics: baseline and at week 12 and 16<br>• Immunogenicity: baseline and weeks 12 and 16