ATI-450 Plus Methotrexate (MTX) Versus Placebo Plus MTX in Participants With Moderate to Severe Active Rheumatoid Arthritis (RA)

Percentage of Participants Achieving ACR20 at Week 12

Timeframe: Week 12

Participants achieving American College of Rheumatology (ACR) 20 (responders) were defined as having ≥20% improvement in both the number of swollen and tender joints (66/68 joint counts) and ≥20% improvement in ≥3 of the following 5 measures: Patient's Global Assessment of Disease Activity (VAS), Patient's Assessment of Arthritis Pain (VAS), Health Assessment Questionnaire-Disability Index (HAQ-DI), Physician's Global Assessment of Disease Activity (VAS), and acute phase reactant as measured by hsCRP. Model-based estimates and 95% confidence intervals (CIs) were produced.

Percentage of Participants Achieving ACR50 at Week 12

Timeframe: Week 12

Participant achieving ACR50 (responders) were defined as having ≥50% improvement in both the number of swollen and tender joints (66/68 joint counts) and ≥50% improvement in ≥3 of the following 5 measures: Patient's Global Assessment of Disease Activity (VAS), Patient's Assessment of Arthritis Pain (VAS), HAQ-DI, Physician's Global Assessment of Disease Activity (VAS), Acute phase reactant as measured by hsCRP. Model-based estimates and 95% CIs were produced.

Percentage of Participants Achieving ACR70 at Week 12

Timeframe: Week 12

Participants achieving ACR70 (responders) were defined as having ≥70% improvement in both the number of swollen and tender joints (66/68 joint counts) and ≥70% improvement in ≥3 of the following 5 measures: Patient's Global Assessment of Disease Activity (VAS), Patient's Assessment of Arthritis Pain (VAS), HAQ-DI, Physician's Global Assessment of Disease Activity (VAS), Acute phase reactant as measured by hsCRP. Model-based estimates and 95% CIs were produced.

Change From Baseline in DAS28-CRP at Week 12

Timeframe: Baseline, Week 12

The DAS28-CRP consists of a composite score of the following variables: TJC28, SJC28, CRP (hsCRP was used for the purposes of this study), and Patient's Global Assessment of Disease Activity. Interpretation of the DAS28-CRP is on a scale of 0 to 9.4, where \<2.6 is considered remission, ≥2.6 to \<3.2 is considered low/minimal disease activity, ≥3.2 to ≤5.1 is considered moderate disease activity, and \>5.1 is considered high/severe disease activity. The least square (LS) mean change from baseline in DAS28-CRP at Week 12 was estimated from the Mixed Model Repeated Measures (MMRM) model.

Percentage of Participants Achieving DAS28-CRP Remission (Score <2.6) at Week 12

Timeframe: Week 12

The Disease Activity Score using 28 Joint Count-C-reactive protein (DAS28-CRP) consists of a composite score of the following variables: TJC28, SJC28, CRP (hsCRP is used for the purposes of this study), and Patient's Global Assessment of Disease Activity. Interpretation of the DAS28-CRP is on a scale of 0 to 9.4, where \<2.6 is considered remission, ≥2.6 to \<3.2 is considered low/minimal disease activity, ≥3.2 to ≤5.1 is considered moderate disease activity, and \>5.1 is considered high/severe disease activity. Model-based estimates and 95% CIs were produced.

Percentage of Participants Achieving DAS28-CRP Low Disease Activity (Score ≤ 3.2) at Week 12

Timeframe: Week 12

The DAS28-CRP consists of a composite score of the following variables: TJC28, SJC28, CRP (hsCRP is used for the purposes of this study), and Patient's Global Assessment of Disease Activity. Interpretation of the DAS28-CRP is on a scale of 0 to 9.4, where \<2.6 is considered remission, ≥2.6 to \<3.2 is considered low/minimal disease activity, ≥3.2 to ≤5.1 is considered moderate disease activity, and \>5.1 is considered high/severe disease activity. Model-based estimates and 95% CIs were produced.

Change From Baseline in HAQ-DI Score at Week12

Timeframe: Baseline, Week 12

The HAQ-DI (standard disability method calculation) was utilized to assess the participant's physical function or disability according to the participant. The HAQ-DI is a 20-item, validated questionnaire used to assess the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities \[errands and chores\]). Responses in each functional area are scored from 0 (no difficulty) to 3 (inability to perform a ask in that area). Overall score was computed as the sum of category scores and divided by the number of categories answered, ranging from 0 to 3. A lower score demonstrated less disability. LS mean change from baseline in HAQ-DI score at Week 12 was estimated from the MMRM model.

Change From Baseline in CDAI Score at Week 12

Timeframe: Baseline, Week 12

The Clinical Disease Activity Index (CDAI) was the sum of 4 outcome parameters: * Tender joint count out of 28 joints (TJC28) * Swollen joint count out of 28 joints (SJC28) * Patient's Global Assessment of Disease Activity; and * Physician's Global Assessment of Disease Activity. Interpretation of the CDAI disease activity was measured on a scale of 0 to 76, where ≤2.8 was considered remission, \>2.8 to ≤10 was considered low/minimal disease activity, \>10 to ≤22 was considered moderate disease activity, and \>22.0 was considered high/severe disease activity. LS mean change from baseline in CDAI score at Week 12 was estimated from the MMRM model.

Percentage of Participants Achieving CDAI Remission (Score ≤ 2.8)

Timeframe: Week 12

The CDAI was the sum of 4 outcome parameters: * Tender joint count out of 28 joints (TJC28) * Swollen joint count out of 28 joints (SJC28) * Patient's Global Assessment of Disease Activity; and * Physician's Global Assessment of Disease Activity. Interpretation of the CDAI disease activity was measured on a scale of 0 to 76, where ≤2.8 was considered remission, \>2.8 to ≤10 was considered low/minimal disease activity, \>10 to ≤22 was considered moderate disease activity, and \>22.0 was considered high/severe disease activity. Model-based estimates and 95% CIs were produced.

Percent Change From Baseline in hsCRP Level at Week 12

Timeframe: Baseline, Week 12

Blood samples were evaluated to measure levels of hsCRP.

Change From Baseline in Short Form Health Survey SF-36 Physical Component Summary (PCS) Score at Week 12

Timeframe: Baseline, Week 12

The PCS is composed of 4 scales of the Short Form-36 Health Status Survey Questionnaire (SF-36) version 2 assessing physical function, role limitations caused by physical problems, bodily pain, and general health. The range of the SF-36 PCS is between 0 and 100, where higher scores represent better physical functioning. A 2.5 to 5-point change from baseline is established as the minimum clinically-important difference for the PCS in RA participants. LS mean change from baseline in SF-36 PCS score at Week 12 was estimated from the MMRM model.

Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-Fatigue) Score at Week 12

Timeframe: Baseline, Week 12

The FACIT-Fatigue is a 13-item questionnaire that measures an individual's level of fatigue during their usual daily activities over the past week. The level of fatigue is measured on a 4 point Likert scale (4 = not at all fatigued to 0 = very much fatigued). The total score range is from 0 to 52. The higher the score, the lower the fatigue level. LS mean change from baseline in FACIT-Fatigue score at Week 12 was estimated from the MMRM model.

ATI-450 and Metabolite (CDD-2164) Concentrations

Timeframe: 2 hours postdose on Days 1, 8, and 85