A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of ABBV-3373 in Participants With Moderate to Severe Rheumatoid Arthritis (RA)
- Conditions
- Rheumatoid Arthritis (RA)
- Interventions
- Registration Number
- NCT03823391
- Lead Sponsor
- AbbVie
- Brief Summary
This study will assess the safety, tolerability, and efficacy of ABBV-3373 in participants with moderately to severely active rheumatoid arthritis (RA) on background methotrexate (MTX) compared with adalimumab.
- Detailed Description
This study consists of a 12-week double-blind active-controlled phase and a 12 week double-blind extension period.
In the active-controlled period of the first 12 weeks of treatment, participants are randomized to receive either ABBV-3373 100 mg intravenously (IV) every other week (EOW) or adalimumab 80 mg subcutaneously (SC) EOW according to a 2:1 ratio.
At Week 12, the administration of ABBV-3373 was to stop to assess the durability of the observed clinical effects up to 24 weeks. Participants randomized to ABBV-3373 were to receive placebo injections, whereas participants randomized into the adalimumab arm were to continue their 80 mg dosing.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 48
- Participant has the clinical diagnosis of RA for > 3 months based on the 1987 American College of Rheumatology (ACR) classification criteria or 2010 ACR/European League against Rheumatism (EULAR) criteria.
- Participant meets the following disease activity criteria: >= 4 swollen joints (based on 28 joint count) and >= 4 tender joints (based on 28 joint count) at Screening and Baseline visits and disease activity score (28 joints) (DAS28) C-reactive protein (CRP) >= 3.2 at Screening.
- Participant has an incomplete response to methotrexate. Participants must have been on oral or parental MTX therapy >= 3 months and on a stable prescription of 15 to 25 mg/week (or >= 10 mg/week in participants intolerant of MTX at doses >= 15 mg/week) for >= 4 weeks prior to the first dose of study drug. Participant must be expected to be able to continue on stable dose of MTX for the duration of study participation.
- Participants previously exposed to adalimumab or other anti-tumor necrosis factor (TNF) biologics.
- Participants previously exposed to non-anti-TNF biologics or targeted synthetic disease-modifying antirheumatic drugs (DMARDs) for RA, with exception of participants exposed for less than 3 months and terminated not due to lack of efficacy or intolerability.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Adalimumab Placebo for ABBV-3373 Participants will be administered with placebo to ABBV-3373 by intravenous infusion and 80 mg adalimumab by subcutaneous injection every other week for 12 weeks. After 12 weeks, participants will receive 80 mg adalimumab subcutaneously every other week until Week 22. Adalimumab Adalimumab Participants will be administered with placebo to ABBV-3373 by intravenous infusion and 80 mg adalimumab by subcutaneous injection every other week for 12 weeks. After 12 weeks, participants will receive 80 mg adalimumab subcutaneously every other week until Week 22. ABBV-3373 Followed by Placebo ABBV-3373 Participants will be administered with 100 mg ABBV-3373 by intravenous infusion and placebo to adalimumab by subcutaneous injection every other week for 12 weeks. After 12 weeks, participants will receive placebo to adalimumab every other week until Week 22. ABBV-3373 Followed by Placebo Placebo for adalimumab Participants will be administered with 100 mg ABBV-3373 by intravenous infusion and placebo to adalimumab by subcutaneous injection every other week for 12 weeks. After 12 weeks, participants will receive placebo to adalimumab every other week until Week 22.
- Primary Outcome Measures
Name Time Method Change From Baseline to Week 12 in Disease Activity Score (DAS) 28 (C-reactive Protein [CRP]) Baseline and Week 12 The DAS28 (CRP) is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (measured on a visual analog scale \[VAS\] from 0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 (CRP) range from 0.96 to approximately 10, where higher scores indicate more disease activity. A negative change from Baseline in DAS28 (CRP) indicates improvement in disease activity.
- Secondary Outcome Measures
Name Time Method Change From Baseline to Week 12 in Clinical Disease Activity Index (CDAI) Baseline and Week 12 The clinical disease activity index (CDAI) is a composite index for assessing disease activity based on the summation of the counts of tender joint count (out of 28 evaluated joints) and swollen joint count (out of 28 evaluated joints), Patient Global Assessment of Disease Activity and Physician Global Assessment of Disease Activity both measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 76 with higher scores indicating higher disease activity. A negative change from Baseline indicates improvement in disease activity.
Change From Baseline in Simplified Disease Activity Index (SDAI) Baseline and Week 12 The SDAI is the numerical sum of five outcome parameters: tender and swollen joint count (based on a 28-joint assessment), Patient Global Assessment of Disease Activity and Physician Global Assessment of Disease Activity both measured on a VAS from 0-10 cm and level of CRP (in mg/dL; normal \< 1 mg/dL). The SDAI has a range from 0 to 86, with higher scores indicating higher disease activity. A negative change from Baseline indicates improvement in disease activity.
Change From Baseline to Week 12 in DAS28 (Erythrocyte Sedimentation Rate [ESR]) Baseline and Week 12 The DAS28 (ESR) is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (measured on a VAS from 0-100 mm), and ESR (in mm/hr). Scores on the DAS28 (ESR) range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change from Baseline indicates improvement in disease activity.
Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28 (CRP) at Week 12 Week 12 The DAS28 (CRP) is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (measured on a VAS from 0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 (CRP) range from 0.96 to approximately 10, where higher scores indicate more disease activity. A DAS28 (CRP) score less than or equal to 3.2 indicates low disease activity.
Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12 Baseline and Week 12 Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR50 response criteria:
1. ≥ 50% improvement in 68-tender joint count;
2. ≥ 50% improvement in 66-swollen joint count; and
3. ≥ 50% improvement in at least 3 of the 5 following parameters:
* Physician global assessment of disease activity
* Patient global assessment of disease activity
* Patient assessment of pain
* Health Assessment Questionnaire - Disability Index (HAQ-DI)
* High-sensitivity C-reactive protein (hsCRP).
Trial Locations
- Locations (30)
PCCR Solution /ID# 215457
🇺🇸Colleyville, Texas, United States
C.V. Mehta MD, Med Corporation /ID# 213068
🇺🇸Hemet, California, United States
Robin K. Dore MD, Inc /ID# 213045
🇺🇸Tustin, California, United States
Rheum Assoc of North Alabama /ID# 213626
🇺🇸Huntsville, Alabama, United States
AZ Arthritis and Rheum Researc /ID# 208515
🇺🇸Phoenix, Arizona, United States
Inland Rheum & Osteo Med Grp /ID# 213044
🇺🇸Upland, California, United States
W. Broward Rheum Assoc Inc. /ID# 211017
🇺🇸Tamarac, Florida, United States
Institute of Arthritis Researc /ID# 213043
🇺🇸Idaho Falls, Idaho, United States
Arthritis Center, Inc. /ID# 213972
🇺🇸Palm Harbor, Florida, United States
Duke Early Phase Research Unit (DCRI) /ID# 213212
🇺🇸Durham, North Carolina, United States
PRN Professional Research Network of Kansas, LLC /ID# 213046
🇺🇸Wichita, Kansas, United States
West Tennessee Research Inst /ID# 208838
🇺🇸Jackson, Tennessee, United States
Trinity Universal Research Association /ID# 209167
🇺🇸Plano, Texas, United States
Paramount Medical Research Con /ID# 209042
🇺🇸Middleburg Heights, Ohio, United States
Charite Research Organisation GmbH /ID# 210216
🇩🇪Berlin, Germany
Debreceni Egyetem Klinikai Kozpont /ID# 210164
🇭🇺Debrecen, Hungary
Reumatika - Centrum Reumatologii NZOZ /ID# 209220
🇵🇱Warsaw, Poland
Sheba Medical Center /ID# 211339
🇮🇱Ramat Gan, Israel
Academisch Medical center Amsterdam /ID# 209303
🇳🇱Amsterdam, Noord-Holland, Netherlands
Mindful Medical Research /ID# 208403
🇵🇷San Juan, Puerto Rico
SANUS Szpital Specjalistyczny /ID# 209022
🇵🇱Stalowa Wola, Poland
STAT Research, Inc. /ID# 213933
🇺🇸Vandalia, Ohio, United States
BayCare Medical Group, Inc. /ID# 213935
🇺🇸Tampa, Florida, United States
Clinvest Research LLC /ID# 215451
🇺🇸Springfield, Missouri, United States
CRU Hungary Egeszsegugyi és Szolgaltato Kft. /ID# 210055
🇭🇺Miskolc, Borsod-Abauj-Zemplen, Hungary
DRC Gyogyszervizsgalo Kozpont Kft. /ID# 210159
🇭🇺Balatonfüred, Veszprem, Hungary
Budai Irgalmasrendi Korhaz /ID# 208877
🇭🇺Budapest, Hungary
Rambam Health Care Campus /ID# 212747
🇮🇱Haifa, Israel
Suncoast Clinical Research /ID# 213973
🇺🇸New Port Richey, Florida, United States
GCM Medical Group, PSC /ID# 208154
🇵🇷San Juan, Puerto Rico