E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with Moderate to Severe Active Rheumatoid Arthritis (RA) who have had an Inadequate Response to MTX Alone |
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E.1.1.1 | Medical condition in easily understood language |
Patients with Moderate to Severe Active Rheumatoid Arthritis (RA) who have had an Inadequate Response to MTX Alone |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
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 efficacy of multiple doses of ATI-450 plus MTX versus placebo plus MTX in Patients with moderate to severe active RA |
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E.2.2 | Secondary objectives of the trial |
1. To assess the efficacy and safety of ATI-450 plus MTX in patients with moderate to severe active RA. 2. To assess the PK of ATI-450 in patients with moderate to severe active RA who are receiving concomitant MTX. 3. To conduct dose response modeling of ATI-450 in patients with moderate to severe RA who are receiving concomitant MTX. 4. Exploratory: To assess the PD of ATI-450 plus MTX in patients with moderate to severe active RA |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Able to comprehend and be willing to sign the Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved patient ICF prior to administration of any study-related procedures. • Diagnosis of adult-onset RA as defined by the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria. • Have active moderate to severe RA at Screening. • A minimum of 12 weeks on MTX with a stable MTX dose. |
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E.4 | Principal exclusion criteria |
• Current acute or chronic immunoinflammatory disease other than RA which may impact the course or assessment of RA. • Uncontrolled non-immunoinflammatory disease that may place the patient at increased risk during the study or impact the interpretation of results (eg, previous malignancy, recurrent infection, previous venous thromboembolism). • Patient has experience with > 2 biologics, > 1 JAK inhibitor, or a combination of 1 biologic experience and 1 JAK inhibitor. • Currently receiving corticosteroids at doses > 10 mg/day of prednisone (or equivalent) or have been receiving an unstable dosing regimen of corticosteroids within 2 weeks of screening |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of patients achieving ACR20 |
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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) |
• Proportion of patients achieving ACR50/70 at Week 12 • Proportion of patients achieving ACR20/50/70 at each scheduled timepoint • Mean change from baseline in DAS28-CRP over time • Proportion of patients achieving DAS28-CRP remission (score < 2.6) at each scheduled timepoint • Proportion of patients achieving DAS28-CRP low disease activity (score ≤ 3.2) at each scheduled timepoint • Mean change from baseline in CDAI over time • Proportion of patients achieving CDAI remission (score ≤ 2.8) at each scheduled timepoint • Percent change from baseline in hsCRP level each scheduled timepoint • HAQ-DI score over time • SF-36v2 score over time • FACIT-Fatigue score over time • AEs, SAEs, vital signs, laboratory values, PEs, and ECGs • Trough ATI-450 and metabolite (CDD-2164) concentrations at clinic visits. On Day 1, 8, and 85, trough and 2-hour post dose will be collected. • Proportion of patients achieving ACR20/50/70 at Week 12 • Change from baseline to Week 12 in DAS28-CRP |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
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 | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 41 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
United States |
Bulgaria |
Czechia |
Poland |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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Date of the last visit or date of last procedure of the last patient in the study |
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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 | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |