Effects of Abatacept in Patients With Early Rheumatoid Arthritis (AVERT-2)

• ClinicalTrials.gov Identifier: NCT02504268
• Recruitment Status: Active, not recruiting
• First Posted: July 21, 2015
• Results First Posted: April 8, 2019
• Last Update Posted: November 27, 2019
• Sponsor: Bristol-Myers Squibb
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: July 20, 2015
• First Posted Date: July 21, 2015
• Results First Submitted Date: January 16, 2019
• Results First Posted Date: April 8, 2019
• Last Update Posted Date: November 27, 2019
• Actual Study Start Date: August 31, 2015
• Actual Primary Completion Date: January 16, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 4, 2019)

Percentage of Subjects in Simple Disease Activity Index (SDAI) Remission at Week 24 [ Time Frame: Week 24 ]

Simple Disease Activity Index (SDAI) is calculated using the following formula: TJC + SJC + PGA + MDGA + CRP (TJC = number of painful joints from 28 joints, SJC = number of swollen joints from 28 joints, PGA = patient global assessment on a visual analog scale 0-10 cm, MDGA = physician global assessment on a visual analog scale 0-10 cm, and CRP = c-reactive protein in mg/dL) SDAI Remission is defined as SDAI <= 3.3. Using a logistic regression model that includes treatment arm, randomization stratification factor, and baseline SDAI as continuous variable and point estimate of adjusted ORs, corresponding 95% CI and p-value was provided. SDAI total score range: 0 to 86. SDAI <= 3.3 indicates disease remission and SDAI >26 = high disease activity.

• Original Primary Outcome Measures (submitted: July 20, 2015): Proportion of subjects in Simple Disease Activity Index (SDAI) remission [ Time Frame: Week 24 ]
• Change History: Complete list of historical versions of study NCT02504268 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: April 4, 2019)

• Percentage of Subjects in Disease Activity Score (DAS)28 - C-reactive Protein (CRP) Remission at Week 24 [ Time Frame: Week 24 ]
  DAS28-CRP = Disease Activity Score 28 based on C-reactive protein DAS28-CRP Remission is defined as DAS28-CRP <= 2.6 Using a logistic regression model that includes treatment arm, stratification variable and baseline measure as continuous variable and point estimate of adjusted ORs, corresponding 95% CI and p-value was provided.
• Percentage of Subjects in SDAI Remission at Week 52 [ Time Frame: Week 52 ]
  Simple Disease Activity Index (SDAI) is calculated using the following formula: TJC + SJC + PGA + MDGA + CRP (TJC = number of painful joints from 28 joints, SJC = number of swollen joints from 28 joints, PGA = patient global assessment on a visual analog scale 0-10 cm, MDGA = physician global assessment on a visual analog scale 0-10 cm, and CRP = c-reactive protein in mg/dL) SDAI Remission is defined as SDAI <= 3.3. Using a logistic regression model that includes treatment arm, randomization stratification factor, and baseline SDAI as continuous variable and point estimate of adjusted ORs, corresponding 95% CI and p-value was provided. SDAI total score range: 0 to 86. SDAI <= 3.3 indicates disease remission and SDAI >26 = high disease activity.
• Mean Change From Baseline in Radiographic Progression of Joint Damage as Measured by Modified Sharp/Van Der Heijide Total Sharp Scores (TSS) at Week 52 [ Time Frame: Week 52 ]
  The Modified Total Sharp Score (mTSS) is calculated as the bilateral sum of erosion and Joint Space Narrowing (JSN) scores across all joints of the hands and feet.The score range for mTSS is 0-448. Higher scores indicate more joint damage. The mean change from baseline in TSS using modified Sharp/van der Heijide scores was assessed using a rank-based nonparametric ANCOVA model.
• Percentage of Subjects in Boolean Remission at Week 52 [ Time Frame: Week 52 ]
  Boolean Remission is defined as Tender joint count less than 1, Swollen joint count less than 1, CRP less than 1 mg/dL, patient global assessment less than 1 (on 0 to 10 VAS scale). Logistic regression was used for this endpoint.

Original Secondary Outcome Measures (submitted: July 20, 2015)

• Proportion of subjects in Disease Activity Index (DAS)28 - c-reactive protein (CRP) remission [ Time Frame: Week 52 ]
• Proportion of subjects in SDAI remission [ Time Frame: Week 52 ]
• Mean change from baseline in radiographic progression of joint damage [ Time Frame: Week 52 ]
• Proportion of subjects in Boolean remission [ Time Frame: Week 52 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Effects of Abatacept in Patients With Early Rheumatoid Arthritis
• Official Title: A Phase 3B, Randomized, Double-Blind Clinical Trial to Evaluate the Efficacy and Safety of Abatacept SC in Combination With Methotrexate Compared to Methotrexate Monotherapy in Achieving Clinical Remission in Adults With Early Rheumatoid Arthritis Who Are Methotrexate Naive
• Brief Summary: The purpose of this study is to determine if abatacept is effective in the treatment of early rheumatoid arthritis.
• Detailed Description: Subcutaneous (SC)
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Rheumatoid Arthritis

Intervention

• Drug: Abatacept
• Drug: Methotrexate
• Other: Abatacept Placebo
• Other: Methotrexate Placebo

Study Arms

• Experimental: Combination Therapy: Abatacept + Methotrexate
  Abatacept 125 mg subcutaneous injection once per week + Methotrexate at least 15mg per week tablet or capsule orally once per week
  Interventions:

  • Drug: Abatacept
  • Drug: Methotrexate
• Active Comparator: Methotrexate treatment
  Methotrexate at least 15mg per week tablet or capsule orally
  Intervention: Drug: Methotrexate
• Placebo Comparator: Abatacept Placebo
  Placebo for Abatacept subcutaneous injection once per week
  Intervention: Other: Abatacept Placebo
• Placebo Comparator: Methotrexate Placebo
  Placebo to match Methotrexate capsule orally once per week
  Intervention: Other: Methotrexate Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: April 4, 2019): 1067
• Original Estimated Enrollment (submitted: July 20, 2015): 1000
• Estimated Study Completion Date: March 20, 2020
• Actual Primary Completion Date: January 16, 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Rheumatoid arthritis (RA) diagnosis less than 6 months
• CRP > 3 mg/L or Erythrocyte Sedimentation Rate (ESR) ≥ 28 mm/h
• At least 3 swollen and 3 tender joints
• Anti-citrullinated protein antibodies (ACPA) positive

Exclusion Criteria:

• At risk for tuberculosis
• Have acute infection
• Have chronic or recurrent bacterial or serious latent viral infection
• History of malignancies in the last 5 years except squamous skin, basal skin or cervical carcinoma
• Previous treatment with any conventional or biologic Disease-modifying anti rheumatic drugs (DMARD)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Austria, Brazil, Canada, Chile, Colombia, Czechia, Finland, France, Germany, Hungary, Israel, Italy, Japan, Korea, Republic of, Mexico, Monaco, Netherlands, Peru, Poland, Qatar, Romania, Russian Federation, Singapore, South Africa, Spain, Sweden, Taiwan, United Kingdom, United States
• Removed Location Countries: Czech Republic, Puerto Rico, Saudi Arabia, United Arab Emirates

Administrative Information

• NCT Number: NCT02504268
• Other Study ID Numbers: IM101-550; 2015-001275-50 ( EudraCT Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Bristol-Myers Squibb
• Study Sponsor: Bristol-Myers Squibb
• Collaborators: Not Provided

Investigators

• Study Director: Bristol Myers Squibb; Bristol-Myers Squibb

• PRS Account: Bristol-Myers Squibb
• Verification Date: November 2019