Back to resultsA Study to Investigate the Safety and Efficacy of ABT-122 Given With Methotrexate in Subjects With Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate
Primary Purpose
Rheumatoid Arthritis
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
adalimumab
ABT-122
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring efficacy, Methotrexate, safety
Eligibility Criteria
Inclusion Criteria:
- Adult male or female, 18 years of age or older.
- Diagnosis of RA based on the 2010 American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) criteria (as defined in the definition of terms).
- Rheumatoid Arthritis (RA) diagnosis at least 3 months from the date of first Screening.
Have active RA defined by minimum disease activity criteria:
- ≥ 6 Swollen joints (based on 66 joint counts) at screening and baseline visits.
- ≥ 6 Tender joints (based on 68 joint counts) at screening and baseline visits.
- hsCRP> ULN OR positive for both Rheumatoid Factor (RF) and Anti-Cyclic Citrullinated Peptide (Anti-CCP) Antibody levels at screening.
- Inadequate response to Methotrexate (MTX) treatment defined as oral or parenteral treatment ≥ 3 months with an unchanged mode of application and stable prescribed MTX dose for at least 4 weeks prior to baseline of ≥ 10mg/week and < the upper limit of the applicable approved local label. Subject can also be on stable doses of sulfasalazine and/or hydroxychloroquine, so long as they are also on methotrexate.
Exclusion Criteria:
- Subject has previous exposure to Humira, other Tumor necrosis factor (TNF) inhibitors or other biological DMARDs.
Current treatment with traditional oral Disease modifying antirheumatic drugs (DMARDs) (except for concomitant treatment with sulfasalazine and/or hydroxychloroquine in addition to MTX). Oral DMARDs must be washed out 5 times the mean terminal elimination half-life of a drug apart from MTX prior to Day 1.
• Subject could have been exposed to prior Janus kinase (JAK) inhibitors so long as they have been off therapy for 5 half-lives.
- Stable prescribed dose of oral prednisone or prednisone equivalent > 10 mg/day within the 30 days of first dose of study drug.
- Intra-articular or parenteral administration of corticosteroids in the preceding 4 weeks of first dose of study drug. Inhaled corticosteroids for stable medical conditions are allowed.
Laboratory values of the following at the Screening Visit:
- Confirmed hemoglobin < 9 g/dL for males and < 8.5 g/dL for females,
- Absolute neutrophil count (ANC) < 1500 mm^3,
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 1.5 × the upper limit of normal (ULN) or bilirubin ≥ 3 mg/dL,
- Serum creatinine > 1.5 × the ULN,
- Platelets < 100,000 cells/[mm3] (10^9/L),
- Clinically significant abnormal screening laboratory results as evaluated by the Investigator.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Active Comparator
Experimental
Experimental
Experimental
Arm Label
Adalimumab 40 mg EOW
ABT-122 60 mg EOW
ABT-122 120 mg EOW
ABT-122 120 mg EW
Arm Description
Adalimumab 40 mg every other week (EOW) for 11 weeks.
ABT-122 60 mg every other week (EOW) for 11 weeks.
ABT-122 120 mg every other week (EOW) for 11 weeks.
ABT-122 120 mg every week (EW) for 11 weeks.
Outcomes
Primary Outcome Measures
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 12
Response defined as at least 20% reduction (improvement) compared with baseline in tender joint count (TJC68), swollen joint count (SJC66), and at least 3 of the 5 remaining ACR core set measures: patient's assessment of pain, patient's global assessment of disease activity (PtGA); physician's global assessment of disease activity (PGA), Health Assessment Questionnaire - Disability Index (HAQ-DI), and high-sensitivity C-reactive protein (hsCRP). Last observation carried forward (LOCF) was used for missing data (only post-baseline values were carried forward).
Secondary Outcome Measures
Change in Disease Activity Score 28 With High Sensitivity C-Reactive Protein (DAS28 [hsCRP])
The DAS28 (hsCRP) is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, hsCRP, and general health are included in the DAS28 (hsCRP) score. Scores range from 0 to 10: a score >5.1 indicates high disease activity, a score <3.2 indicates low disease activity, and a score <2.6 indicates clinical remission. A negative change from baseline represents improvement. n=the number of participants with evaluable data at each time point. LOCF was used (only post-baseline values were carried forward).
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Week 12
Response defined as at least 50% reduction (improvement) compared with baseline in tender joint count (TJC68), swollen joint count (SJC66), and at least 3 of the 5 remaining ACR core set measures: patient's assessment of pain, PtGA; PGA, HAQ-DI, and hsCRP. LOCF was used (only post-baseline values were carried forward).
Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response at Week 12
Response defined as at least 70% reduction (improvement) compared with baseline in tender joint count (TJC68), swollen joint count (SJC66), and at least 3 of the 5 remaining ACR core set measures: patient's assessment of pain, PtGA; PGA, HAQ-DI, and hsCRP. LOCF was used (only post-baseline values were carried forward).
Percentage of Participants Achieving Low Disease Activity (LDA) or Clinical Remission (CR) Based on DAS28 (hsCRP) at Week 12
The DAS28 (hsCRP) is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, hsCRP, and general health are included in the DAS28 (hsCRP) score. Scores range from 0 to 10: a score >5.1 indicates high disease activity, a score <3.2 indicates low disease activity, and a score <2.6 indicates clinical remission. LDA is defined as a DAS28 (hsCRP) score from 2.6 to < 3.2 at Week 12. CR is defined as a DAS28 (hsCRP) score < 2.6 at Week 12. LOCF was used (only post-baseline values were carried forward).
Percentage of Participants Achieving CR Based on DAS28 (hsCRP) at Week 12
The DAS28 (hsCRP) is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, hsCRP, and general health are included in the DAS28 (hsCRP) score. Scores range from 0 to 10: a score >5.1 indicates high disease activity, a score <3.2 indicates low disease activity, and a score <2.6 indicates clinical remission. CR is defined as a DAS28 (hsCRP) score < 2.6 at Week 12. LOCF was used (only post-baseline values were carried forward).
Percentage of Participants Achieving LDA or CR Based on Clinical Disease Activity Index (CDAI) at Week 12
The clinical disease activity index (CDAI) is a composite index for assessing disease activity based on the summation of the counts of TJC28 and SJC28, patient global assessment of disease activity measured on a VAS from 0 to 10 cm, and physician global assessment of disease activity measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity. LDA is defined as a CDAI score from 2.8 to ≤ 10 at Week 12. CR is defined as a CDAI score ≤ 2.8 at Week 12. LOCF was used (only post-baseline values were carried forward).
Percentage of Participants Achieving CR Based on Clinical Disease Activity Index (CDAI) at Week 12
The clinical disease activity index (CDAI) is a composite index for assessing disease activity based on the summation of the counts of TJC28 and SJC28, patient global assessment of disease activity measured on a VAS from 0 to 10 cm, and physician global assessment of disease activity measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity. CR is defined as a CDAI score ≤ 2.8 at Week 12. LOCF was used (only post-baseline values were carried forward).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02141997
Brief Title
A Study to Investigate the Safety and Efficacy of ABT-122 Given With Methotrexate in Subjects With Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate
Official Title
A Phase 2 Study to Investigate the Safety and Efficacy of ABT-122 Given With Methotrexate in Subjects With Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate
Study Type
Interventional
2. Study Status
Record Verification Date
September 2016
Overall Recruitment Status
Completed
Study Start Date
July 2014 (undefined)
Primary Completion Date
September 2015 (Actual)
Study Completion Date
November 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AbbVie
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study is a Phase 2 randomized, double-blind, double-dummy, parallel-group study designed to assess the safety, tolerability, efficacy, pharmacokinetics and immunogenicity of multiple doses of ABT 122 in subjects with active rheumatoid arthritis (RA) who are inadequately responding to methotrexate (MTX) treatment.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
efficacy, Methotrexate, safety
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
222 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Adalimumab 40 mg EOW
Arm Type
Active Comparator
Arm Description
Adalimumab 40 mg every other week (EOW) for 11 weeks.
Arm Title
ABT-122 60 mg EOW
Arm Type
Experimental
Arm Description
ABT-122 60 mg every other week (EOW) for 11 weeks.
Arm Title
ABT-122 120 mg EOW
Arm Type
Experimental
Arm Description
ABT-122 120 mg every other week (EOW) for 11 weeks.
Arm Title
ABT-122 120 mg EW
Arm Type
Experimental
Arm Description
ABT-122 120 mg every week (EW) for 11 weeks.
Intervention Type
Biological
Intervention Name(s)
adalimumab
Other Intervention Name(s)
Humira
Intervention Description
adalimumab administered as subcutaneous injection every other week (EOW)
Intervention Type
Biological
Intervention Name(s)
ABT-122
Intervention Description
ABT-122 administered as subcutaneous injection every other week (EOW)
Primary Outcome Measure Information:
Title
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 12
Description
Response defined as at least 20% reduction (improvement) compared with baseline in tender joint count (TJC68), swollen joint count (SJC66), and at least 3 of the 5 remaining ACR core set measures: patient's assessment of pain, patient's global assessment of disease activity (PtGA); physician's global assessment of disease activity (PGA), Health Assessment Questionnaire - Disability Index (HAQ-DI), and high-sensitivity C-reactive protein (hsCRP). Last observation carried forward (LOCF) was used for missing data (only post-baseline values were carried forward).
Time Frame
Baseline (Day 1) and Week 12
Secondary Outcome Measure Information:
Title
Change in Disease Activity Score 28 With High Sensitivity C-Reactive Protein (DAS28 [hsCRP])
Description
The DAS28 (hsCRP) is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, hsCRP, and general health are included in the DAS28 (hsCRP) score. Scores range from 0 to 10: a score >5.1 indicates high disease activity, a score <3.2 indicates low disease activity, and a score <2.6 indicates clinical remission. A negative change from baseline represents improvement. n=the number of participants with evaluable data at each time point. LOCF was used (only post-baseline values were carried forward).
Time Frame
Baseline, Weeks 2, 4, 6, 8, and 12
Title
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Week 12
Description
Response defined as at least 50% reduction (improvement) compared with baseline in tender joint count (TJC68), swollen joint count (SJC66), and at least 3 of the 5 remaining ACR core set measures: patient's assessment of pain, PtGA; PGA, HAQ-DI, and hsCRP. LOCF was used (only post-baseline values were carried forward).
Time Frame
Baseline (Day 1) and Week 12
Title
Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response at Week 12
Description
Response defined as at least 70% reduction (improvement) compared with baseline in tender joint count (TJC68), swollen joint count (SJC66), and at least 3 of the 5 remaining ACR core set measures: patient's assessment of pain, PtGA; PGA, HAQ-DI, and hsCRP. LOCF was used (only post-baseline values were carried forward).
Time Frame
Baseline (Day 1) and Week 12
Title
Percentage of Participants Achieving Low Disease Activity (LDA) or Clinical Remission (CR) Based on DAS28 (hsCRP) at Week 12
Description
The DAS28 (hsCRP) is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, hsCRP, and general health are included in the DAS28 (hsCRP) score. Scores range from 0 to 10: a score >5.1 indicates high disease activity, a score <3.2 indicates low disease activity, and a score <2.6 indicates clinical remission. LDA is defined as a DAS28 (hsCRP) score from 2.6 to < 3.2 at Week 12. CR is defined as a DAS28 (hsCRP) score < 2.6 at Week 12. LOCF was used (only post-baseline values were carried forward).
Time Frame
Week 12
Title
Percentage of Participants Achieving CR Based on DAS28 (hsCRP) at Week 12
Description
The DAS28 (hsCRP) is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, hsCRP, and general health are included in the DAS28 (hsCRP) score. Scores range from 0 to 10: a score >5.1 indicates high disease activity, a score <3.2 indicates low disease activity, and a score <2.6 indicates clinical remission. CR is defined as a DAS28 (hsCRP) score < 2.6 at Week 12. LOCF was used (only post-baseline values were carried forward).
Time Frame
Week 12
Title
Percentage of Participants Achieving LDA or CR Based on Clinical Disease Activity Index (CDAI) at Week 12
Description
The clinical disease activity index (CDAI) is a composite index for assessing disease activity based on the summation of the counts of TJC28 and SJC28, patient global assessment of disease activity measured on a VAS from 0 to 10 cm, and physician global assessment of disease activity measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity. LDA is defined as a CDAI score from 2.8 to ≤ 10 at Week 12. CR is defined as a CDAI score ≤ 2.8 at Week 12. LOCF was used (only post-baseline values were carried forward).
Time Frame
Week 12
Title
Percentage of Participants Achieving CR Based on Clinical Disease Activity Index (CDAI) at Week 12
Description
The clinical disease activity index (CDAI) is a composite index for assessing disease activity based on the summation of the counts of TJC28 and SJC28, patient global assessment of disease activity measured on a VAS from 0 to 10 cm, and physician global assessment of disease activity measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity. CR is defined as a CDAI score ≤ 2.8 at Week 12. LOCF was used (only post-baseline values were carried forward).
Time Frame
Week 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adult male or female, 18 years of age or older.
Diagnosis of RA based on the 2010 American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) criteria (as defined in the definition of terms).
Rheumatoid Arthritis (RA) diagnosis at least 3 months from the date of first Screening.
Have active RA defined by minimum disease activity criteria:
≥ 6 Swollen joints (based on 66 joint counts) at screening and baseline visits.
≥ 6 Tender joints (based on 68 joint counts) at screening and baseline visits.
hsCRP> ULN OR positive for both Rheumatoid Factor (RF) and Anti-Cyclic Citrullinated Peptide (Anti-CCP) Antibody levels at screening.
Inadequate response to Methotrexate (MTX) treatment defined as oral or parenteral treatment ≥ 3 months with an unchanged mode of application and stable prescribed MTX dose for at least 4 weeks prior to baseline of ≥ 10mg/week and < the upper limit of the applicable approved local label. Subject can also be on stable doses of sulfasalazine and/or hydroxychloroquine, so long as they are also on methotrexate.
Exclusion Criteria:
Subject has previous exposure to Humira, other Tumor necrosis factor (TNF) inhibitors or other biological DMARDs.
Current treatment with traditional oral Disease modifying antirheumatic drugs (DMARDs) (except for concomitant treatment with sulfasalazine and/or hydroxychloroquine in addition to MTX). Oral DMARDs must be washed out 5 times the mean terminal elimination half-life of a drug apart from MTX prior to Day 1.
• Subject could have been exposed to prior Janus kinase (JAK) inhibitors so long as they have been off therapy for 5 half-lives.
Stable prescribed dose of oral prednisone or prednisone equivalent > 10 mg/day within the 30 days of first dose of study drug.
Intra-articular or parenteral administration of corticosteroids in the preceding 4 weeks of first dose of study drug. Inhaled corticosteroids for stable medical conditions are allowed.
Laboratory values of the following at the Screening Visit:
Confirmed hemoglobin < 9 g/dL for males and < 8.5 g/dL for females,
Absolute neutrophil count (ANC) < 1500 mm^3,
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 1.5 × the upper limit of normal (ULN) or bilirubin ≥ 3 mg/dL,
Serum creatinine > 1.5 × the ULN,
Platelets < 100,000 cells/[mm3] (10^9/L),
Clinically significant abnormal screening laboratory results as evaluated by the Investigator.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Heikki Mansikka, MD
Organizational Affiliation
AbbVie
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
29855172
Citation
Genovese MC, Weinblatt ME, Aelion JA, Mansikka HT, Peloso PM, Chen K, Li Y, Othman AA, Khatri A, Khan NS, Padley RJ. ABT-122, a Bispecific Dual Variable Domain Immunoglobulin Targeting Tumor Necrosis Factor and Interleukin-17A, in Patients With Rheumatoid Arthritis With an Inadequate Response to Methotrexate: A Randomized, Double-Blind Study. Arthritis Rheumatol. 2018 Nov;70(11):1710-1720. doi: 10.1002/art.40580. Epub 2018 Oct 10.
Results Reference
derived
Links:
URL
http://rxabbvie.com
Description
Humira Prescribing info
Learn more about this trial
A Study to Investigate the Safety and Efficacy of ABT-122 Given With Methotrexate in Subjects With Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate
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