E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Active Rheumatoid Arthritis |
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E.1.1.1 | Medical condition in easily understood language |
Rheumatoid Arthritis is a chronic inflammatory disease characterised by joint swelling, joint tenderness, and destruction of synovial joints, leading to severe disability and premature mortality. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039073 |
E.1.2 | Term | Rheumatoid arthritis |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 |
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E.2.2 | Secondary objectives of the trial |
• 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 • To examine the pharmacokinetic and pharmacodynamic effects of AMT-101 • To examine the immunogenicity of AMT-101
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Female and male patients aged ≥18 years old, 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 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).
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E.4 | Principal 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
• Proportion of patients with treatment-emergent adverse events (TEAEs), SAEs, and discontinuation due to TEAEs • Assessment of physical examinations, laboratory parameters, vital signs, and ECGs |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Efficacy: Change over time in: - DAS-28(CRP), SDAI and CDAI, ACR 20, 50,70 - Proportion of patients with DAS-28(CRP) less than 2.6 - Proportion of patients with DAS-28(CRP) less than 3.2 - Proportion of patients with Boolean Remission - Change in acute phase reactants (CRP, ESR) • Pharmacokinetics: Change in AMT-101 and Serum IL-10 levels • Pharmacodynamics: Change in Rheumatoid Factor, anti-citrullinated Cyclic Peptide antibody levels • Immunogenicity: Incidence of anti-AMT-101 antibodies |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Efficacy: at treatment completion and 4 weeks post completion • Pharmacokinetics: baseline, Day 1- at 8 and 24 hrs. and at weeks 2, 4, 8, and 12 • Pharmacodynamics: baseline and at week 12 and 16 • Immunogenicity: baseline and weeks 12 and 16 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | |