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)

• ClinicalTrials.gov Identifier: NCT04888585
• Recruitment Status: Active, not recruiting
• First Posted: May 17, 2021
• Last Update Posted: November 10, 2022
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Tracking Information

• First Submitted Date: May 13, 2021
• First Posted Date: May 17, 2021
• Last Update Posted Date: November 10, 2022
• Actual Study Start Date: June 2, 2021
• Actual Primary Completion Date: August 25, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 13, 2021)

Percentage of Participants Achieving American College of Rheumatology 50 % (ACR50) Response [ Time Frame: At 12 weeks ]

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 measured on a Numerical Rating Scale of 0 to 10 (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).

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 13, 2021)

• Change in Disease Activity Score (DAS) 28 (CRP) from Baseline [ Time Frame: Up to 12 weeks ]
  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.
• Change in Clinical Disease Activity Index (CDAI) from Baseline [ Time Frame: Up to 12 weeks ]
  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 [ Time Frame: At 12 weeks ]
  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 [ Time Frame: At 12 weeks ]
  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 [ Time Frame: At 12 weeks ]
  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 [ Time Frame: At 12 weeks ]
  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 [ Time Frame: At 12 weeks ]
  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 [ Time Frame: At 12 weeks ]
  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 in the Health Assessment Questionnaire Disability Index (HAQ-DI) From Baseline [ Time Frame: Up to 12 weeks ]
  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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• Official Title: A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of ABBV-154 in Subjects With Moderately to Severely Active Rheumatoid Arthritis With Inadequate Response to Biologic and/or Targeted Synthetic Disease-Modifying Anti-Rheumatic Drugs (b/tsDMARDs)

Brief Summary

Rheumatoid Arthritis (RA) is an inflammatory disease of the joints causing pain, stiffness, swelling and loss of joint function. This study evaluates how safe and effective ABBV-154 is in participants treated for moderately to severely active RA. Adverse events and change in the disease activity will be assessed.

ABBV-154 is an investigational drug being evaluated for the treatment of RA. Study doctors place the participants in 1 of 5 treatment groups or arms, each arm receiving a different treatment. There is a 1 in 5 chance that participants will be assigned to placebo. Participants 18-75 years of age with moderate to severe RA will be enrolled. Around 425 participants will be enrolled in the study in approximately 270 sites worldwide.

The study is compromised 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 will be re-randomized to receive ABBV-154 in 2 different doses SC every other week (eow). Other participants will remain on their previous dose and dosing regimen of ABBV-154.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Rheumatoid Arthritis (RA)

Intervention

• Drug: ABBV-154
  Subcutaneous Injection
• Drug: Placebo
  Subcutaneous Injection

Study Arms

• Experimental: Dose A of 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.
  Intervention: Drug: ABBV-154
• Experimental: Dose B of 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.
  Intervention: Drug: ABBV-154
• Experimental: Dose C of ABBV-154 EOW
  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.
  Intervention: Drug: ABBV-154
• Experimental: Dose C of ABBV-154 E4W
  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.
  Intervention: Drug: ABBV-154
• Experimental: 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.
  Interventions:

  • Drug: ABBV-154
  • Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: June 7, 2022): 473
• Original Estimated Enrollment (submitted: May 13, 2021): 425
• Estimated Study Completion Date: February 5, 2026
• Actual Primary Completion Date: August 25, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• 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).

Exclusion Criteria:

- Participant discontinued prior adalimumab therapy due to intolerability or toxicity.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, Czechia, Germany, Greece, Hungary, Israel, Italy, Japan, Korea, Republic of, Netherlands, New Zealand, Poland, Puerto Rico, Russian Federation, Slovakia, Spain, Taiwan, Turkey, Ukraine, United States
• Removed Location Countries: France, United Kingdom

Administrative Information

• NCT Number: NCT04888585
• Other Study ID Numbers: M20-466; 2020-005303-39 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
• URL: https://vivli.org/ourmember/abbvie/

• Current Responsible Party: AbbVie
• Original Responsible Party: Same as current
• Current Study Sponsor: AbbVie
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: ABBVIE INC.; AbbVie

• PRS Account: AbbVie
• Verification Date: November 2022