Study to Evaluate Adverse Events and Change in Disease Activity in Participants Between 18 to 75 Years of Age Treated With Subcutaneous (SC) Injections of ABBV-154 for Moderately to Severely Active Rheumatoid Arthritis (RA)
- Registration Number
- NCT04888585
- Lead Sponsor
- AbbVie
- Brief Summary
Rheumatoid Arthritis (RA) is an inflammatory disease of the joints causing pain, stiffness, swelling and loss of joint function. This study evaluated how safe and effective ABBV-154 is in participants treated for moderately to severely active RA. Adverse events and change in the disease activity were assessed.
ABBV-154 is an investigational drug being evaluated for the treatment of RA. Study doctors placed the participants in 1 of 5 treatment groups or arms; each arm received a different treatment. There was a 1 in 5 chance that participants were assigned to placebo. Participants 18-75 years of age with moderate to severe RA were enrolled. Around 425 participants were to be enrolled in the study at approximately 270 sites worldwide.
The study was comprised of a 12 week placebo-controlled period, a double-blind long term extension (LTE) period 1 of 66 weeks, a LTE period 2 of 104 weeks and a follow-up visit 70 days after the last dose of the study drug. In the LTE period 1, participants in the placebo group were re-randomized to receive ABBV-154 at 1 of 2 different doses SC every other week (EOW). Other participants remained on their previous dose and dosing regimen of ABBV-154.
There may have been a higher treatment burden for participants in this trial compared to their standard of care. Participants attended regular visits during the study at a hospital or clinic. The effect of the treatment was checked by medical assessments, blood tests, and side effects, and completing questionnaires.
- Detailed Description
Participants were randomly assigned at a ratio of 1:1:1:1:1 to ABBV-154 at either 40 mg, 150 mg, 340 mg, subcutaneously (SC) EOW; 340 mg SC every 4 weeks (E4W); or placebo SC EOW. Randomization was stratified by baseline glucocorticoid (yes/no); number of prior failed biologic and/or targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) (1; 2 or more); and prior anti-TNF failure (yes/no) and if yes, further stratification by prior adalimumab use (yes/no).
After 12 weeks, participants receiving placebo were re-randomized to receive ABBV-154 150 mg SC EOW or 340 mg SC EOW for the long-term extension (LTE) periods. At re-randomization, participants were stratified by baseline glucocorticoid use (yes/no) and prior adalimumab use (yes/no). Participants from the other dose groups were to continue with their respective dose and dosing regimen.
The primary analysis was conducted after all ongoing participants completed Week 12 or withdrew from the study. A final analysis was to be conducted after all participants completed LTE period 2 and a safety follow-up visit or withdrew from the study. The study was terminated before any participants entered LTE Period 2.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 473
- Clinical diagnosis of rheumatoid arthritis(RA) with fulfillment of the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for RA.
- Participant has >= 6 swollen joints (based on 66 joint count) and >=6 tender joints (based on 68 joint count) at baseline.
- Participant must have had an inadequate response to at least one prior biologic and/or targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) treatment for RA.
- Participants must be on stable dose of methotrexate (MTX).
- Participant discontinued prior adalimumab therapy due to intolerability or toxicity.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Participants in this group will receive placebo SC eow for 12 weeks in the placebo-controlled period and will be re-randomized in 1:1 ratio to receive ABBV-154 dose B or C respectively SC eow for 66 weeks in the LTE period 1 and 104 weeks in LTE period 2. Dose A of ABBV-154 ABBV-154 Participants in this group will receive dose A of ABBV-154 subcutaneously (SC) every other week (eow) for 12 weeks in the placebo-controlled period, 66 weeks in the long term extension (LTE) period 1 and 104 weeks in LTE period 2. Dose B of ABBV-154 ABBV-154 Participants in this group will receive dose B of ABBV-154 SC eow for 12 weeks in the placebo-controlled period, 66 weeks in the LTE period 1 and 104 weeks in LTE period 2. Dose C of ABBV-154 EOW ABBV-154 Participants in this group will receive dose C of ABBV-154 SC eow for 12 weeks in the placebo-controlled period, 66 weeks in the LTE period 1 and 104 weeks in LTE period 2. Dose C of ABBV-154 E4W ABBV-154 Participants in this group will receive dose C of ABBV-154 SC every 4 weeks (e4w) for 12 weeks in the placebo-controlled period, 66 weeks in the LTE period 1 and 104 weeks in LTE period 2. Placebo ABBV-154 Participants in this group will receive placebo SC eow for 12 weeks in the placebo-controlled period and will be re-randomized in 1:1 ratio to receive ABBV-154 dose B or C respectively SC eow for 66 weeks in the LTE period 1 and 104 weeks in LTE period 2.
- Primary Outcome Measures
Name Time Method Achievement of 50% Improvement as Measured by American College of Rheumatology Response Criteria (ACR50) at Week 12 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's Global Assessment of Disease Activity (NRS)
* Patient's Global Assessment of Disease Activity (NRS)
* Patient's Assessment of Pain (NRS)
* Health Assessment Questionnaire - Disability Index (HAQ-DI)
* High-sensitivity C-reactive protein (hsCRP).
- Secondary Outcome Measures
Name Time Method Change From Baseline in Disease Activity Score (DAS) 28 (CRP) at Week 12 Baseline to Week 12 The DAS28 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 (NRS), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change from Baseline in DAS28 (CRP) indicates improvement in disease activity.
Change in Clinical Disease Activity Index (CDAI) at Week 12 Baseline to Week 12 CDAI is a composite index for assessing disease activity based on the sum of the total tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (NRS), and Physician's Global Assessment of Disease Activity (NRS). The total CDAI score ranges from 0 to 76 with higher scores indicating higher disease activity.
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 12 Week 12 Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR20 response criteria:
1. ≥ 20% improvement in 68-tender joint count;
2. ≥ 20% improvement in 66-swollen joint count; and
3. ≥ 20% improvement in at least 3 of the 5 following parameters:
* Physician's Global Assessment of Disease Activity (NRS)
* Patient's Global Assessment of Disease Activity (NRS)
* Patient's Assessment of Pain (NRS)
* Health Assessment Questionnaire - Disability Index (HAQ-DI)
* High-sensitivity C-reactive protein (hsCRP).Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response at Week 12 Week 12 Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR70 response criteria:
1. ≥ 70% improvement in 68-tender joint count;
2. ≥ 70% improvement in 66-swollen joint count; and
3. ≥ 70% improvement in at least 3 of the 5 following parameters:
* Physician's Global Assessment of Disease Activity (NRS)
* Patient's Global Assessment of Disease Activity (NRS)
* Patient's Assessment of Pain (NRS)
* Health Assessment Questionnaire - Disability Index (HAQ-DI)
* High-sensitivity C-reactive protein (hsCRP).Percentage of Participants Achieving Low Disease Activity (LDA) Defined by DAS28 (CRP) <= 3.2 at Week 12 Week 12 Low disease activity (LDA) was defined as a DAS28 score less than or equal to 3.2. The DAS28 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 (NRS) and Physician's Global Assessment of Disease Activity (NRS), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity.
Percentage of Participants Achieving LDA Defined by CDAI <= 10 at Week 12 Week 12 Low disease activity based on CDAI is defined as a CDAI score less than or equal to 10. CDAI is a composite index for assessing disease activity based on the sum of the total tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (NRS), and Physician's Global Assessment of Disease Activity (NRS). The total CDAI score ranges from 0 to 76 with higher scores indicating higher disease activity.
Percentage of Participants Achieving Clinical Remission (CR) Defined by DAS28 (CRP) < 2.6 at Week 12 Week 12 Clinical remission was defined as a DAS28 (CRP) score less than 2.6. The DAS28 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 (NRS), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity.
Percentage of Participants Achieving CR Defined by CDAI <= 2.8 at Week 12 Week 12 Clinical Remission was defined by CDAI as a score less than or equal to 2.8. CDAI is a composite index for assessing disease activity based on the summation of the total tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (NRS), and Physician's Global Assessment of Disease Activity (NRS). The total CDAI score ranges from 0 to 76 with higher scores indicating higher disease activity.
Change From Baseline in the Health Assessment Questionnaire Disability Index (HAQ-DI) to Week 12 Baseline to Week 12 The Health Assessment Questionnaire - Disability Index is a participant-reported questionnaire that measures the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores) over the past week. Participants assessed their ability to do each task on a scale from 0 (without any difficulty) to 3 (unable to do). Scores were averaged to provide an overall score ranging from 0 to 3, where 0 represents no disability and 3 represents very severe, high-dependency disability. A negative change from Baseline in the overall score indicates improvement.
Trial Locations
- Locations (220)
Purushotham & Akther Kotha MD, Inc /ID# 228120
🇺🇸La Mesa, California, United States
International Medical Research /ID# 228069
🇺🇸Daytona Beach, Florida, United States
Neoclinical Research /ID# 228753
🇺🇸Hialeah, Florida, United States
Omega Research Group /ID# 229966
🇺🇸Orlando, Florida, United States
Dr Naik-Medical Professional Corporation-Alliance Health /ID# 227823
🇨🇦Saskatoon, Saskatchewan, Canada
Aotearoa Clinical Trials /ID# 229012
🇳🇿Papatoetoe, Auckland, New Zealand
ClinicMed Daniluk, Nowak Sp.k. /ID# 227919
🇵🇱Bialystok, Podlaskie, Poland
MICS Centrum Medyczne Warszawa /ID# 231133
🇵🇱Warsaw, Poland
Hospital Regional Universitario de Malaga /ID# 227418
🇪🇸Malaga, Spain
MNI City Multidisciplinary Hospital #18 Kharkiv City Council /ID# 228961
🇺🇦Kharkiv, Ukraine
Scroll for more (210 remaining)Purushotham & Akther Kotha MD, Inc /ID# 228120🇺🇸La Mesa, California, United States