A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of ABBV-3373 in Participants With Moderate to Severe Rheumatoid Arthritis (RA)

A Randomized, Double-Blind, Double-Dummy, Active Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of ABBV-3373 in Subjects With Moderate to Severe Rheumatoid Arthritis

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.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis (RA)
• Intervention / Treatment: Drug: ABBV-3373; Drug: Placebo for adalimumab; Drug: Placebo for ABBV-3373; Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Charite Research Organisation GmbH /ID# 210216
• Hungary
  • Budapest, Hungary, 1023
    • Budai Irgalmasrendi Korhaz /ID# 208877
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem Klinikai Kozpont /ID# 210164
  • Borsod-Abauj-Zemplen
    • Miskolc, Borsod-Abauj-Zemplen, Hungary, 3529
      • CRU Hungary Egeszsegugyi és Szolgaltato Kft. /ID# 210055
  • Veszprem
    • Balatonfüred, Veszprem, Hungary, 8230
      • DRC Gyogyszervizsgalo Kozpont Kft. /ID# 210159
• Israel
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus /ID# 212747
  • Ramat Gan, Israel, 5239424
    • Sheba Medical Center /ID# 211339
• Netherlands
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1105 AZ
      • Academisch Medical center Amsterdam /ID# 209303
• Poland
  • Stalowa Wola, Poland, 37-450
    • SANUS Szpital Specjalistyczny /ID# 209022
  • Warsaw, Poland, 02-691
    • Reumatika - Centrum Reumatologii NZOZ /ID# 209220
• Puerto Rico
  • San Juan, Puerto Rico, 00909
    • GCM Medical Group, PSC /ID# 208154
  • San Juan, Puerto Rico, 00918-3756
    • Mindful Medical Research /ID# 208403
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • Rheum Assoc of North Alabama /ID# 213626
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • AZ Arthritis and Rheum Researc /ID# 208515
  • California
    • Hemet, California, United States, 92543
      • C.V. Mehta MD, Med Corporation /ID# 213068
    • Tustin, California, United States, 92780
      • Robin K. Dore MD, Inc /ID# 213045
    • Upland, California, United States, 91786
      • Inland Rheum & Osteo Med Grp /ID# 213044
  • Florida
    • New Port Richey, Florida, United States, 34652
      • Suncoast Clinical Research /ID# 213973
    • Palm Harbor, Florida, United States, 34684
      • Arthritis Center, Inc. /ID# 213972
    • Tamarac, Florida, United States, 33321
      • W. Broward Rheum Assoc Inc. /ID# 211017
    • Tampa, Florida, United States, 33614-7101
      • BayCare Medical Group, Inc. /ID# 213935
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Institute of Arthritis Researc /ID# 213043
  • Kansas
    • Wichita, Kansas, United States, 67205
      • PRN Professional Research Network of Kansas, LLC /ID# 213046
  • Missouri
    • Springfield, Missouri, United States, 65810-2607
      • Clinvest Research LLC /ID# 215451
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Early Phase Research Unit (DCRI) /ID# 213212
  • Ohio
    • Middleburg Heights, Ohio, United States, 44130
      • Paramount Medical Research Con /ID# 209042
    • Vandalia, Ohio, United States, 45377-9464
      • STAT Research, Inc. /ID# 213933
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • West Tennessee Research Inst /ID# 208838
  • Texas
    • Colleyville, Texas, United States, 76034
      • PCCR Solution /ID# 215457
    • Plano, Texas, United States, 75024-5283
      • Trinity Universal Research Association /ID# 209167

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ABBV-3373 Followed by Placebo; 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.	Drug: ABBV-3373; ABBV-3373 is administered as intravenous (IV) infusion; Drug: Placebo for adalimumab; Placebo for adalimumab is administered as subcutaneous (SC) injection
Experimental: 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.	Drug: Placebo for ABBV-3373; Placebo for ABBV-3373 is administered as IV infusion; Drug: Adalimumab; Adalimumab is administered as subcutaneous (SC) injection; Other Names: Humira

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 12 in Disease Activity Score (DAS) 28 (C-reactive Protein [CRP])	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.	Baseline and Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 12 in Clinical Disease Activity Index (CDAI)	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.	Baseline and Week 12
Change From Baseline in Simplified Disease Activity Index (SDAI)	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.	Baseline and Week 12
Change From Baseline to Week 12 in DAS28 (Erythrocyte Sedimentation Rate [ESR])	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.	Baseline and Week 12
Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28 (CRP) at 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.	Week 12
Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12	Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR50 response criteria: ≥ 50% improvement in 68-tender joint count;; ≥ 50% improvement in 66-swollen joint count; and; ≥ 50% improvement in at least 3 of the 5 following parameters:Physician global assessment of disease activityPatient global assessment of disease activityPatient assessment of painHealth Assessment Questionnaire - Disability Index (HAQ-DI)High-sensitivity C-reactive protein (hsCRP).	Baseline and Week 12

Collaborators and Investigators

• Sponsor: AbbVie

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2019
• Primary Completion (Actual): April 8, 2020
• Study Completion (Actual): August 26, 2020

Study Registration Dates

• First Submitted: January 29, 2019
• First Submitted That Met QC Criteria: January 29, 2019
• First Posted (Actual): January 30, 2019

Study Record Updates

• Last Update Posted (Actual): July 19, 2021
• Last Update Submitted That Met QC Criteria: June 29, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Adalimumab; Rheumatoid Arthritis (RA); ABBV-3373
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Anti-Inflammatory Agents; Antirheumatic Agents; Adalimumab
• Other Study ID Numbers: M16-560; 2018-003053-21 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD 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 and 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.
• IPD Sharing Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
• IPD Sharing 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 (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• 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.: Yes