Rheumatoid Arthritis
Conditions
Keywords
Arthritis, Rheumatoid
Brief summary
This is a Phase 2 study to investigate the safety, tolerability, PK, and PD of ATI-450 plus methotrexate versus methotrexate alone in patients with moderate to severe RA.
Detailed description
This is a Phase 2, randomized, investigator and patient-blind, sponsor-unblinded, parallel group, placebo-controlled study to investigate the safety, tolerability, PK, and PD of ATI-450 plus methotrexate versus methotrexate alone in patients with moderate to severe RA with inadequate response to methotrexate. All subjects will be required to complete a safety follow up visit 30 days post last study medication administration.
Interventions
DRUGATI-450
Oral, small molecule MK2 inhibitor
DRUGPlacebo oral tablet
Placebo tablet manufactured to match ATI-450 in appearance
DRUGMethotrexate
7.5 mg to 25 mg weekly
Sponsors
Aclaris Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The blinded placebo drug is packaged to match the active study drug and will be stored under the same conditions.
Intervention model description
Randomized, investigator and patient-blind, sponsor-unblinded, parallel group.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of adult-onset RA as defined by the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria. * DAS28-CRP ≥3.2 defined as moderate to high disease activity. * Have moderately to severely active RA defined by at least 4/28 tender and 4/28 swollen joints. * hsCRP ≥5 mg/L at screening. * Patients must have definitive intra-articular synovitis or osteitis defined as a score of 1 or greater on a Hand-Wrist MRI as assessed by central imaging reader (using RAMRIS). * On a stable MTX dose and a stable dose of folic or folinic acid prior to the screening visit.
Exclusion criteria
* Patient has a current acute or chronic immunoinflammatory disease other than RA which may impact the course or assessment of RA. * Patient has an uncontrolled non-immunoinflammatory disease that may place the patient at increased risk during the study or impact the interpretation of results. * History or evidence of active or latent tuberculosis. * Active infection requiring treatment with antibiotics. * Blood pressure levels (in supine position after at least 5 minutes rest): \<90 mmHg or \>140 mmHg for systolic blood pressure or \<40 mmHg or \>90 mmHg for diastolic blood pressure. * Are currently receiving corticosteroids at doses greater than 10 mg per day of prednisone (or equivalent) or have been receiving an unstable dosing regimen of corticosteroids within 2 weeks of the screening visit. * Have started treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or have been receiving an unstable dosing regimen of NSAIDs within 2 weeks of the screening visit. * Patients with history of stroke. * Any joint procedure in the past 90 days prior to screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Primary Outcome Measure is the Determination of the Safety and Tolerability of ATI-450 Plus Methotrexate in Patients With Moderate to Severe Rheumatoid Arthritis: Adverse Events (AEs) | Baseline through Day 114 | Safety and tolerability reported as Adverse Events (AEs). AEs will be coded with the Medical Dictionary for Regulatory Activities (MedDRA) version 23.0. AEs will be presented by system organ class and preferred term in frequency tables. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Disease Activity Score | Baseline through Day 114 | The Disease Activity Score using 28 joint count C-reactive protein DAS28 (CRP) consists of a composite score of the following variables: tender joint count, swollen joint count, CRP, and Patient's Global Assessment of Disease Activity score. The following equation will be used to calculate the DAS28 (CRP): DAS28 (CRP) = 0.56 √TJC28 + 0.28√SJC28 + 0.36ln(CRP +1) + 0.014×(Patient's Global Assessment of Disease Activity) + 0.96, where: * TJC28 = number of joints tender out of 28 * SJC28 = number of joints swollen out of 28 * CRP = C-reactive protein * Patient's Global Assessment of Disease Activity on a 100 mm visual analog scale (VAS) recorded by the patient Interpretation of the DAS28 (CRP) disease activity measure is on a scale of 0 to 9.4, where: \<2.6 is considered remission, ≥2.6 to \<3.2 is considered low/minimal, ≥3.2 to ≤5.1 is considered moderate, and \>5.1 is considered high/severe. |
| Number and Percent of Patients Achieving DAS28-CRP <2.6 Over Time | Baseline through Day 114 | Number and Percent of Patients Achieving DAS28-CRP \<2.6 over time |
| Change From Baseline in RAMRIS Hand-Wrist Assessments (Osteitis Average) | Baseline through Day 84 | Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) uses integer scales to measure the severity of disease at each bone or joint of interest in the hand and wrist, with separate scores given for osteitis and synovitis. Osteitis was scored at 25 bone locations: distal radius and ulna, 8 carpal bones (trapezium, trapezoid, capitate, hamate, pisiform, scaphoid, lunate, and triquetrum, as well as the 5 metacarpal bases), 5 metacarpal heads, and 5 proximal phalangeal bases. Score Definition 0 No osteitis 1. 1-33% involvement of original articular bone 2. 34-67% involvement of original articular bone 3. 68-100% involvement of original articular bone Synovitis was scored at the following 8 joint locations: distal radioulnar joint, radiocarpal joint, intercarpal / carpometacarpal joints 2-5, and 5 metacarpophalangeal (MCP) joints. Score Definition 0 No synovitis 1. 1-33% volume enhancement 2. 34-67% volume enhancement 3. 68-100% volume enhancement |
| Change From Baseline in RAMRIS Hand-Wrist Assessments (Synovitis Average) | Baseline through Day 84 | Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) uses integer scales to measure the severity of disease at each bone or joint of interest in the hand and wrist, with separate scores given for osteitis and synovitis. Osteitis was scored at 25 bone locations: distal radius and ulna, 8 carpal bones (trapezium, trapezoid, capitate, hamate, pisiform, scaphoid, lunate, and triquetrum, as well as the 5 metacarpal bases), 5 metacarpal heads, and 5 proximal phalangeal bases. Score Definition 0 No osteitis 1. 1-33% involvement of original articular bone 2. 34-67% involvement of original articular bone 3. 68-100% involvement of original articular bone Synovitis was scored at the following 8 joint locations: distal radioulnar joint, radiocarpal joint, intercarpal / carpometacarpal joints 2-5, and 5 metacarpophalangeal (MCP) joints. Score Definition 0 No synovitis 1. 1-33% volume enhancement 2. 34-67% volume enhancement 3. 68-100% volume enhancement |
| Percent Change in (hsCRP) Levels Over Time | Baseline through Day 114 | Median percent change from baseline in high sensitivity C-reactive protein (hsCRP) levels over time |
| Number and Percent of Patients Achieving ACR 50 | Baseline through Day 114 | American College of Rheumatology (ACR) 50 will be calculated at each treatment visit and the number and percent of subjects with a 50% improvement will be tabulated at each scheduled visit. |
| Number and Percent of Patients Achieving ACR 70 | Baseline through Day 114 | American College of Rheumatology (ACR) 70 will be calculated at each treatment visit and the number and percent of subjects with a 70% improvement will be tabulated at each scheduled visit. |
| Assessment of ATI-450 Concentration (ng/mL) | Day 1 through Day Day 84 | — |
| Number and Percent of Patients Achieving ACR 20 | Baseline through Day 114 | American College of Rheumatology (ACR) 20 will be calculated at each treatment visit and the number and percent of subjects with a 20% improvement will be tabulated at each scheduled visit. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ATI-450 Plus Methotrexate ATI-450 50mg oral tablet BID with a stable weekly dose of Methotrexate
ATI-450: Oral, small molecule MK2 inhibitor
Methotrexate: 7.5 mg to 25 mg weekly | 16 |
| Placebo Plus Methotrexate Placebo oral tablet BID with a stable weekly dose of Methotrexate
Placebo oral tablet: Placebo tablet manufactured to match ATI-450 in appearance
Methotrexate: 7.5 mg to 25 mg weekly | 3 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | ATI-450 Plus Methotrexate | Placebo Plus Methotrexate | Total |
|---|---|---|---|
| Age, Customized | 55.9 years STANDARD_DEVIATION 9.93 | 55.3 years STANDARD_DEVIATION 6.81 | 55.8 years STANDARD_DEVIATION 9.34 |
| BMI (kg/m2) | 33.37 kg/m2 STANDARD_DEVIATION 8.829 | 36.53 kg/m2 STANDARD_DEVIATION 4.737 | 33.87 kg/m2 STANDARD_DEVIATION 8.298 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 0 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 3 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Height (cm) | 166.94 cm STANDARD_DEVIATION 12.648 | 164.43 cm STANDARD_DEVIATION 3.092 | 166.54 cm STANDARD_DEVIATION 11.63 |
| Region of Enrollment United States | 16 participants | 3 participants | 19 participants |
| Sex: Female, Male Female | 11 Participants | 3 Participants | 14 Participants |
| Sex: Female, Male Male | 5 Participants | 0 Participants | 5 Participants |
| Weight (kg) | 92.74 kg STANDARD_DEVIATION 25.504 | 98.93 kg STANDARD_DEVIATION 14.616 | 93.72 kg STANDARD_DEVIATION 23.899 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 3 |
| other Total, other adverse events | 8 / 16 | 2 / 3 |
| serious Total, serious adverse events | 1 / 16 | 0 / 3 |
Outcome results
Primary
The Primary Outcome Measure is the Determination of the Safety and Tolerability of ATI-450 Plus Methotrexate in Patients With Moderate to Severe Rheumatoid Arthritis: Adverse Events (AEs)
Safety and tolerability reported as Adverse Events (AEs). AEs will be coded with the Medical Dictionary for Regulatory Activities (MedDRA) version 23.0. AEs will be presented by system organ class and preferred term in frequency tables.
Time frame: Baseline through Day 114
Population: The Safety population consisted of patients who receive at least 1 dose of study drug. This set was used for the safety data summaries and baseline characteristic summaries. This set was analyzed as treated.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ATI-450 Plus Methotrexate | The Primary Outcome Measure is the Determination of the Safety and Tolerability of ATI-450 Plus Methotrexate in Patients With Moderate to Severe Rheumatoid Arthritis: Adverse Events (AEs) | 8 Participants |
| Placebo Plus Methotrexate | The Primary Outcome Measure is the Determination of the Safety and Tolerability of ATI-450 Plus Methotrexate in Patients With Moderate to Severe Rheumatoid Arthritis: Adverse Events (AEs) | 2 Participants |
Secondary
Assessment of ATI-450 Concentration (ng/mL)
Time frame: Day 1 through Day Day 84
Population: The PK population consisted of all patients who received at least 1 dose of study drug and provided at least 1 plasma concentration value. This set was analyzed as treated.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ATI-450 Plus Methotrexate | Assessment of ATI-450 Concentration (ng/mL) | Day 84 (2 Hours Postdose) | 293.00 ATI-450 concentration (ng/mL) | Standard Deviation 98.643 |
| ATI-450 Plus Methotrexate | Assessment of ATI-450 Concentration (ng/mL) | Day 56 (Predose) | 153.45 ATI-450 concentration (ng/mL) | Standard Deviation 89.092 |
| ATI-450 Plus Methotrexate | Assessment of ATI-450 Concentration (ng/mL) | Day 1 (2 Hours Postdose) | 225.87 ATI-450 concentration (ng/mL) | Standard Deviation 78.603 |
| ATI-450 Plus Methotrexate | Assessment of ATI-450 Concentration (ng/mL) | Day 7 (Predose) | 163.97 ATI-450 concentration (ng/mL) | Standard Deviation 85.538 |
| ATI-450 Plus Methotrexate | Assessment of ATI-450 Concentration (ng/mL) | Day 14 (Predose) | 131.51 ATI-450 concentration (ng/mL) | Standard Deviation 55.175 |
| ATI-450 Plus Methotrexate | Assessment of ATI-450 Concentration (ng/mL) | Day 28 (Predose) | 135.67 ATI-450 concentration (ng/mL) | Standard Deviation 84.454 |
| ATI-450 Plus Methotrexate | Assessment of ATI-450 Concentration (ng/mL) | Day 42 (Predose) | 170.84 ATI-450 concentration (ng/mL) | Standard Deviation 99.863 |
| ATI-450 Plus Methotrexate | Assessment of ATI-450 Concentration (ng/mL) | Day 84 (Predose) | 124.71 ATI-450 concentration (ng/mL) | Standard Deviation 69.437 |
Secondary
Change From Baseline in Disease Activity Score
The Disease Activity Score using 28 joint count C-reactive protein DAS28 (CRP) consists of a composite score of the following variables: tender joint count, swollen joint count, CRP, and Patient's Global Assessment of Disease Activity score. The following equation will be used to calculate the DAS28 (CRP): DAS28 (CRP) = 0.56 √TJC28 + 0.28√SJC28 + 0.36ln(CRP +1) + 0.014×(Patient's Global Assessment of Disease Activity) + 0.96, where: * TJC28 = number of joints tender out of 28 * SJC28 = number of joints swollen out of 28 * CRP = C-reactive protein * Patient's Global Assessment of Disease Activity on a 100 mm visual analog scale (VAS) recorded by the patient Interpretation of the DAS28 (CRP) disease activity measure is on a scale of 0 to 9.4, where: \<2.6 is considered remission, ≥2.6 to \<3.2 is considered low/minimal, ≥3.2 to ≤5.1 is considered moderate, and \>5.1 is considered high/severe.
Time frame: Baseline through Day 114
Population: The Per-Protocol (PP) population consisted of all patients who completed their Day 84 visit and had valid hsCRP values for at least 6 of the 7 scheduled collection times. This set was analyzed as treated.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ATI-450 Plus Methotrexate | Change From Baseline in Disease Activity Score | Baseline | 5.72 score on a scale | Standard Deviation 0.97 |
| ATI-450 Plus Methotrexate | Change From Baseline in Disease Activity Score | Week 1 | 4.33 score on a scale | Standard Deviation 1.611 |
| ATI-450 Plus Methotrexate | Change From Baseline in Disease Activity Score | Week 2 | 4.26 score on a scale | Standard Deviation 1.57 |
| ATI-450 Plus Methotrexate | Change From Baseline in Disease Activity Score | Week 4 | 4.11 score on a scale | Standard Deviation 1.351 |
| ATI-450 Plus Methotrexate | Change From Baseline in Disease Activity Score | Week 6 | 4.25 score on a scale | Standard Deviation 1.436 |
| ATI-450 Plus Methotrexate | Change From Baseline in Disease Activity Score | Week 8 | 3.84 score on a scale | Standard Deviation 1.383 |
| ATI-450 Plus Methotrexate | Change From Baseline in Disease Activity Score | Week 12 | 3.70 score on a scale | Standard Deviation 1.574 |
| ATI-450 Plus Methotrexate | Change From Baseline in Disease Activity Score | Follow-up | 4.21 score on a scale | Standard Deviation 1.705 |
| Placebo Plus Methotrexate | Change From Baseline in Disease Activity Score | Follow-up | 4.95 score on a scale | Standard Deviation 0.495 |
| Placebo Plus Methotrexate | Change From Baseline in Disease Activity Score | Baseline | 6.00 score on a scale | Standard Deviation 0.99 |
| Placebo Plus Methotrexate | Change From Baseline in Disease Activity Score | Week 6 | 6.15 score on a scale | Standard Deviation 0.495 |
| Placebo Plus Methotrexate | Change From Baseline in Disease Activity Score | Week 1 | 6.15 score on a scale | Standard Deviation 0.495 |
| Placebo Plus Methotrexate | Change From Baseline in Disease Activity Score | Week 12 | 6.35 score on a scale | Standard Deviation 0.212 |
| Placebo Plus Methotrexate | Change From Baseline in Disease Activity Score | Week 2 | 5.25 score on a scale | Standard Deviation 0.354 |
| Placebo Plus Methotrexate | Change From Baseline in Disease Activity Score | Week 8 | 6.20 score on a scale | Standard Deviation 0.424 |
| Placebo Plus Methotrexate | Change From Baseline in Disease Activity Score | Week 4 | 5.75 score on a scale | Standard Deviation 1.061 |
Secondary
Change From Baseline in RAMRIS Hand-Wrist Assessments (Osteitis Average)
Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) uses integer scales to measure the severity of disease at each bone or joint of interest in the hand and wrist, with separate scores given for osteitis and synovitis. Osteitis was scored at 25 bone locations: distal radius and ulna, 8 carpal bones (trapezium, trapezoid, capitate, hamate, pisiform, scaphoid, lunate, and triquetrum, as well as the 5 metacarpal bases), 5 metacarpal heads, and 5 proximal phalangeal bases. Score Definition 0 No osteitis 1. 1-33% involvement of original articular bone 2. 34-67% involvement of original articular bone 3. 68-100% involvement of original articular bone Synovitis was scored at the following 8 joint locations: distal radioulnar joint, radiocarpal joint, intercarpal / carpometacarpal joints 2-5, and 5 metacarpophalangeal (MCP) joints. Score Definition 0 No synovitis 1. 1-33% volume enhancement 2. 34-67% volume enhancement 3. 68-100% volume enhancement
Time frame: Baseline through Day 84
Population: The Per-Protocol (PP) population consisted of all patients who completed their Day 84 visit and had valid hsCRP values for at least 6 of the 7 scheduled collection times. This set was analyzed as treated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ATI-450 Plus Methotrexate | Change From Baseline in RAMRIS Hand-Wrist Assessments (Osteitis Average) | 0.97 Change in Osteitis average | Standard Deviation 1.943 |
| Placebo Plus Methotrexate | Change From Baseline in RAMRIS Hand-Wrist Assessments (Osteitis Average) | 0.88 Change in Osteitis average | Standard Deviation 1.237 |
Secondary
Change From Baseline in RAMRIS Hand-Wrist Assessments (Synovitis Average)
Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) uses integer scales to measure the severity of disease at each bone or joint of interest in the hand and wrist, with separate scores given for osteitis and synovitis. Osteitis was scored at 25 bone locations: distal radius and ulna, 8 carpal bones (trapezium, trapezoid, capitate, hamate, pisiform, scaphoid, lunate, and triquetrum, as well as the 5 metacarpal bases), 5 metacarpal heads, and 5 proximal phalangeal bases. Score Definition 0 No osteitis 1. 1-33% involvement of original articular bone 2. 34-67% involvement of original articular bone 3. 68-100% involvement of original articular bone Synovitis was scored at the following 8 joint locations: distal radioulnar joint, radiocarpal joint, intercarpal / carpometacarpal joints 2-5, and 5 metacarpophalangeal (MCP) joints. Score Definition 0 No synovitis 1. 1-33% volume enhancement 2. 34-67% volume enhancement 3. 68-100% volume enhancement
Time frame: Baseline through Day 84
Population: The Per-Protocol (PP) population consisted of all patients who completed their Day 84 visit and had valid hsCRP values for at least 6 of the 7 scheduled collection times. This set was analyzed as treated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ATI-450 Plus Methotrexate | Change From Baseline in RAMRIS Hand-Wrist Assessments (Synovitis Average) | 0.08 Change in Synovitis average | Standard Deviation 1.894 |
| Placebo Plus Methotrexate | Change From Baseline in RAMRIS Hand-Wrist Assessments (Synovitis Average) | 1.50 Change in Synovitis average | Standard Deviation 2.121 |
Secondary
Number and Percent of Patients Achieving ACR 20
American College of Rheumatology (ACR) 20 will be calculated at each treatment visit and the number and percent of subjects with a 20% improvement will be tabulated at each scheduled visit.
Time frame: Baseline through Day 114
Population: The Per-Protocol (PP) population consisted of all patients who completed their Day 84 visit and had valid hsCRP values for at least 6 of the 7 scheduled collection times. This set was analyzed as treated.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ATI-450 Plus Methotrexate | Number and Percent of Patients Achieving ACR 20 | Week 4 | 8 Participants |
| ATI-450 Plus Methotrexate | Number and Percent of Patients Achieving ACR 20 | Week 8 | 8 Participants |
| ATI-450 Plus Methotrexate | Number and Percent of Patients Achieving ACR 20 | Week 12 | 9 Participants |
| ATI-450 Plus Methotrexate | Number and Percent of Patients Achieving ACR 20 | Follow-up | 6 Participants |
| Placebo Plus Methotrexate | Number and Percent of Patients Achieving ACR 20 | Follow-up | 1 Participants |
| Placebo Plus Methotrexate | Number and Percent of Patients Achieving ACR 20 | Week 4 | 0 Participants |
| Placebo Plus Methotrexate | Number and Percent of Patients Achieving ACR 20 | Week 12 | 0 Participants |
| Placebo Plus Methotrexate | Number and Percent of Patients Achieving ACR 20 | Week 8 | 0 Participants |
Secondary
Number and Percent of Patients Achieving ACR 50
American College of Rheumatology (ACR) 50 will be calculated at each treatment visit and the number and percent of subjects with a 50% improvement will be tabulated at each scheduled visit.
Time frame: Baseline through Day 114
Population: The Per-Protocol (PP) population consisted of all patients who completed their Day 84 visit and had valid hsCRP values for at least 6 of the 7 scheduled collection times. This set was analyzed as treated.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ATI-450 Plus Methotrexate | Number and Percent of Patients Achieving ACR 50 | Week 4 | 2 Participants |
| ATI-450 Plus Methotrexate | Number and Percent of Patients Achieving ACR 50 | Week 8 | 4 Participants |
| ATI-450 Plus Methotrexate | Number and Percent of Patients Achieving ACR 50 | Week 12 | 5 Participants |
| ATI-450 Plus Methotrexate | Number and Percent of Patients Achieving ACR 50 | Follow-up | 3 Participants |
| Placebo Plus Methotrexate | Number and Percent of Patients Achieving ACR 50 | Follow-up | 0 Participants |
| Placebo Plus Methotrexate | Number and Percent of Patients Achieving ACR 50 | Week 4 | 0 Participants |
| Placebo Plus Methotrexate | Number and Percent of Patients Achieving ACR 50 | Week 12 | 0 Participants |
| Placebo Plus Methotrexate | Number and Percent of Patients Achieving ACR 50 | Week 8 | 0 Participants |
Secondary
Number and Percent of Patients Achieving ACR 70
American College of Rheumatology (ACR) 70 will be calculated at each treatment visit and the number and percent of subjects with a 70% improvement will be tabulated at each scheduled visit.
Time frame: Baseline through Day 114
Population: The Per-Protocol (PP) population consisted of all patients who completed their Day 84 visit and had valid hsCRP values for at least 6 of the 7 scheduled collection times. This set was analyzed as treated.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ATI-450 Plus Methotrexate | Number and Percent of Patients Achieving ACR 70 | Week 4 | 0 Participants |
| ATI-450 Plus Methotrexate | Number and Percent of Patients Achieving ACR 70 | Week 8 | 3 Participants |
| ATI-450 Plus Methotrexate | Number and Percent of Patients Achieving ACR 70 | Week 12 | 3 Participants |
| ATI-450 Plus Methotrexate | Number and Percent of Patients Achieving ACR 70 | Follow-up | 0 Participants |
| Placebo Plus Methotrexate | Number and Percent of Patients Achieving ACR 70 | Follow-up | 0 Participants |
| Placebo Plus Methotrexate | Number and Percent of Patients Achieving ACR 70 | Week 4 | 0 Participants |
| Placebo Plus Methotrexate | Number and Percent of Patients Achieving ACR 70 | Week 12 | 0 Participants |
| Placebo Plus Methotrexate | Number and Percent of Patients Achieving ACR 70 | Week 8 | 0 Participants |
Secondary
Number and Percent of Patients Achieving DAS28-CRP <2.6 Over Time
Number and Percent of Patients Achieving DAS28-CRP \<2.6 over time
Time frame: Baseline through Day 114
Population: The Per-Protocol (PP) population consisted of all patients who completed their Day 84 visit and had valid hsCRP values for at least 6 of the 7 scheduled collection times. This set was analyzed as treated.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ATI-450 Plus Methotrexate | Number and Percent of Patients Achieving DAS28-CRP <2.6 Over Time | Baseline | 0 Participants |
| ATI-450 Plus Methotrexate | Number and Percent of Patients Achieving DAS28-CRP <2.6 Over Time | Week 1 | 2 Participants |
| ATI-450 Plus Methotrexate | Number and Percent of Patients Achieving DAS28-CRP <2.6 Over Time | Week 2 | 3 Participants |
| ATI-450 Plus Methotrexate | Number and Percent of Patients Achieving DAS28-CRP <2.6 Over Time | Week 4 | 2 Participants |
| ATI-450 Plus Methotrexate | Number and Percent of Patients Achieving DAS28-CRP <2.6 Over Time | Week 6 | 1 Participants |
| ATI-450 Plus Methotrexate | Number and Percent of Patients Achieving DAS28-CRP <2.6 Over Time | Week 8 | 2 Participants |
| ATI-450 Plus Methotrexate | Number and Percent of Patients Achieving DAS28-CRP <2.6 Over Time | Week 12 | 3 Participants |
| ATI-450 Plus Methotrexate | Number and Percent of Patients Achieving DAS28-CRP <2.6 Over Time | Follow-up | 4 Participants |
| Placebo Plus Methotrexate | Number and Percent of Patients Achieving DAS28-CRP <2.6 Over Time | Follow-up | 0 Participants |
| Placebo Plus Methotrexate | Number and Percent of Patients Achieving DAS28-CRP <2.6 Over Time | Baseline | 0 Participants |
| Placebo Plus Methotrexate | Number and Percent of Patients Achieving DAS28-CRP <2.6 Over Time | Week 6 | 0 Participants |
| Placebo Plus Methotrexate | Number and Percent of Patients Achieving DAS28-CRP <2.6 Over Time | Week 1 | 0 Participants |
| Placebo Plus Methotrexate | Number and Percent of Patients Achieving DAS28-CRP <2.6 Over Time | Week 12 | 0 Participants |
| Placebo Plus Methotrexate | Number and Percent of Patients Achieving DAS28-CRP <2.6 Over Time | Week 2 | 0 Participants |
| Placebo Plus Methotrexate | Number and Percent of Patients Achieving DAS28-CRP <2.6 Over Time | Week 8 | 0 Participants |
| Placebo Plus Methotrexate | Number and Percent of Patients Achieving DAS28-CRP <2.6 Over Time | Week 4 | 0 Participants |
Secondary
Percent Change in (hsCRP) Levels Over Time
Median percent change from baseline in high sensitivity C-reactive protein (hsCRP) levels over time
Time frame: Baseline through Day 114
Population: The Per-Protocol (PP) population consisted of all patients who completed their Day 84 visit and had valid hsCRP values for at least 6 of the 7 scheduled collection times. This set was analyzed as treated.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| ATI-450 Plus Methotrexate | Percent Change in (hsCRP) Levels Over Time | Week 1 | -75.00 Percent Change from Baseline hsCRP |
| ATI-450 Plus Methotrexate | Percent Change in (hsCRP) Levels Over Time | Week 8 | -74.20 Percent Change from Baseline hsCRP |
| ATI-450 Plus Methotrexate | Percent Change in (hsCRP) Levels Over Time | Week 4 | -51.10 Percent Change from Baseline hsCRP |
| ATI-450 Plus Methotrexate | Percent Change in (hsCRP) Levels Over Time | Week 12 | -42.60 Percent Change from Baseline hsCRP |
| ATI-450 Plus Methotrexate | Percent Change in (hsCRP) Levels Over Time | Week 2 | -72.40 Percent Change from Baseline hsCRP |
| ATI-450 Plus Methotrexate | Percent Change in (hsCRP) Levels Over Time | Follow-up | -15.60 Percent Change from Baseline hsCRP |
| ATI-450 Plus Methotrexate | Percent Change in (hsCRP) Levels Over Time | Week 6 | -57.60 Percent Change from Baseline hsCRP |
| Placebo Plus Methotrexate | Percent Change in (hsCRP) Levels Over Time | Follow-up | -40.65 Percent Change from Baseline hsCRP |
| Placebo Plus Methotrexate | Percent Change in (hsCRP) Levels Over Time | Week 1 | -16.50 Percent Change from Baseline hsCRP |
| Placebo Plus Methotrexate | Percent Change in (hsCRP) Levels Over Time | Week 2 | 15.50 Percent Change from Baseline hsCRP |
| Placebo Plus Methotrexate | Percent Change in (hsCRP) Levels Over Time | Week 4 | -50.20 Percent Change from Baseline hsCRP |
| Placebo Plus Methotrexate | Percent Change in (hsCRP) Levels Over Time | Week 6 | 3.00 Percent Change from Baseline hsCRP |
| Placebo Plus Methotrexate | Percent Change in (hsCRP) Levels Over Time | Week 8 | 78.50 Percent Change from Baseline hsCRP |
| Placebo Plus Methotrexate | Percent Change in (hsCRP) Levels Over Time | Week 12 | 7.30 Percent Change from Baseline hsCRP |