Rheumatoid ArthritisPhase 2NCT02141997
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
A Phase 2 study testing adalimumab and ABT-122 in people with Rheumatoid Arthritis, run by AbbVie.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- adalimumab and ABT-122
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 222 participants
- Where
- No sites listed yet
- Study dates
- Jul 2014to Nov 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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:
Show all 12Show fewer
- 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.
About this study
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
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.
- Conditions
- Rheumatoid Arthritis
- Being tested
- adalimumab, ABT-122
- Keywords
- efficacy, Methotrexate, safety
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
adalimumabBiological
Also called Humira
adalimumab administered as subcutaneous injection every other week (EOW)
ABT-122Biological
ABT-122 administered as subcutaneous injection every other week (EOW)
| Study group | Role | What they receive |
|---|---|---|
| Adalimumab 40 mg EOW | Active comparator | Adalimumab 40 mg every other week (EOW) for 11 weeks. Receives: Biological: adalimumab |
| ABT-122 60 mg EOW | Experimental | ABT-122 60 mg every other week (EOW) for 11 weeks. Receives: Biological: ABT-122 |
| ABT-122 120 mg EOW | Experimental | ABT-122 120 mg every other week (EOW) for 11 weeks. Receives: Biological: ABT-122 |
| ABT-122 120 mg EW | Experimental | ABT-122 120 mg every week (EW) for 11 weeks. Receives: Biological: ABT-122 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Baseline (Day 1) and Week 12
Secondary outcomes (7)
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).
Measured: Baseline, Weeks 2, 4, 6, 8, and 12
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).
Measured: Baseline (Day 1) and Week 12
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).
Measured: Baseline (Day 1) and Week 12
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).
Measured: Week 12
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).
Measured: Week 12
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).
Measured: Week 12
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).
Measured: Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2014 (estimated)
- Study startJul 2014
- Primary completionSep 2015
- Study completionNov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by AbbVieThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 222 participants (actual)
Sponsor and investigators
- Lead sponsor
- AbbVie
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Heikki Mansikka, MD, Study director, AbbVie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02141997
- Sponsor's protocol ID
- M12-963
- Other IDs
- 2013-004019-37
- Status last verified
- Sep 2016
- First submitted
- 16 May 2014
- Last updated
- 11 Nov 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 29855172
Study at a glance
From the registry record, last updated by the sponsor on 11 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02141997
- Acronym / sponsor ID
- M12-963
- Conditions
- Rheumatoid Arthritis
- Keywords
- efficacy, Methotrexate, safety
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 222 participants (actual)
- Lead sponsor
- AbbVieIndustry (pharma, biotech, devices)
- Study start
- Jul 2014
- Primary completion
- Sep 2015 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 20 May 2014 (estimated)
- Results
- Posted 11 Nov 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Adalimumab 40 mg EOW | Active comparator | Biological: adalimumabAdalimumab 40 mg every other week (EOW) for 11 weeks. |
| ABT-122 60 mg EOW | Experimental | Biological: ABT-122ABT-122 60 mg every other week (EOW) for 11 weeks. |
| ABT-122 120 mg EOW | Experimental | Biological: ABT-122ABT-122 120 mg every other week (EOW) for 11 weeks. |
| ABT-122 120 mg EW | Experimental | Biological: ABT-122ABT-122 120 mg every week (EW) for 11 weeks. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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:
- 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.
Key exclusion criteria (12 listed)
- 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.
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| adalimumabAlso: Humiraadalimumab administered as subcutaneous injection every other week (EOW) | Biological | Adalimumab 40 mg EOW |
| ABT-122ABT-122 administered as subcutaneous injection every other week (EOW) | Biological | ABT-122 120 mg EOW, ABT-122 120 mg EW, ABT-122 60 mg EOW |
Primary outcome
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 12
Time frame: Baseline (Day 1) and 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).
7 secondary outcomes
Change in Disease Activity Score 28 With High Sensitivity C-Reactive Protein (DAS28 [hsCRP])
Time frame: Baseline, Weeks 2, 4, 6, 8, and 12
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Week 12
Time frame: Baseline (Day 1) and Week 12
Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response at Week 12
Time frame: Baseline (Day 1) and Week 12
Percentage of Participants Achieving Low Disease Activity (LDA) or Clinical Remission (CR) Based on DAS28 (hsCRP) at Week 12
Time frame: Week 12
Percentage of Participants Achieving CR Based on DAS28 (hsCRP) at Week 12
Time frame: Week 12
Percentage of Participants Achieving LDA or CR Based on Clinical Disease Activity Index (CDAI) at Week 12
Time frame: Week 12
Percentage of Participants Achieving CR Based on Clinical Disease Activity Index (CDAI) at Week 12
Time frame: Week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Nov 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29855172Genovese 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.
- Humira Prescribing infoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Heikki Mansikka, MD study director
AbbVie
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing adalimumab and ABT-122 in people with Rheumatoid Arthritis, run by AbbVie.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Nov 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 12 (time frame: Baseline (Day 1) and Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02141997, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Nov 2016.