Psoriatic Arthritis
Conditions
Keywords
Safety, Efficacy, Methotrexate
Brief summary
This study is a Phase 2 randomized, double-blind, double-dummy, active- and placebo-controlled, parallel-group study designed to assess the safety, tolerability, efficacy, pharmacokinetics and immunogenicity of multiple doses of ABT-122 in participants with active PsA who are inadequately responding to MTX treatment.
Interventions
BIOLOGICALadalimumab
BIOLOGICALABT-122
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* PsA diagnosis of at least 3 months duration prior to the date of first screening with ClASsification of Psoriatic ARthritis (CASPAR) confirmed diagnosis at Screening. * Have active psoriasis defined by at least 1 psoriasis lesion \>= 2 cm diameter in areas other than the axilla or groin. * Have active arthritis defined by minimum disease activity criteria: 1. \>= 3 swollen joints (based on 66 joint counts) at Screening 2. \>= 3 tender joints (based on 68 joint counts) at Screening * On a stable dose of methotrexate (MTX) defined as: 1. Oral or parenteral treatment \>= 3 months 2. On a stable dose with an unchanged mode of application for at least 4 weeks prior to baseline 3. Stable MTX dose of \>= 10 mg/week and \<= the upper limit of the applicable approved local label 4. Can also be on stable doses of nonsteroidal anti-inflammatory drugs, sulfasalazine and/or hydroxychloroquine as long as they are also on methotrexate
Exclusion criteria
* Up to 30% (approximately 66 subjects) with prior exposure to a TNF inhibitor may be enrolled if the TNF inhibitor was not discontinued due to lack of efficacy or safety concerns. Subjects must be washed out for at least 5 half-lives of these drugs prior to the Baseline visit. * Subjects on prior adalimumab may not be enrolled in the study * Prior exposure to other non-TNF inhibitor biological disease-modifying antirheumatic drugs (DMARDs) will be permitted if the subject is washed out at least 5 half-lives of these drugs prior to the baseline visit. * Current treatment with traditional oral/intramuscular DMARDs, including conventional synthetic DMARDs (csDMARDs; except for concomitant treatment with sulfasalazine and/or hydroxychloroquine in addition to MTX). Oral DMARDs must be washed out for at least 5 half-lives of a drug apart from MTX prior to the Baseline visit. a. Subject could have been exposed to prior Janus kinase (JAK) or phosphodiesterase type 4 (PDE4) inhibitors so long as they have been off therapy for at least 5 half-lives. * Stable prescribed dose of oral prednisone or prednisone equivalent \> 10 mg/day within the 30 days of the Baseline visit. * Intra-articular or parenteral administration of corticosteroids in the preceding 4 weeks of the Baseline visit. Inhaled corticosteroids for stable medical conditions are allowed. * Laboratory values of the following at the Screening Visit: 1. Confirmed hemoglobin \< 9 g/dL for males and \< 8.5 g/dL for females 2. Absolute neutrophil count (ANC) \< 1500 mm\^3, (or \< 1200 cells/µL for subjects of African descent who are black) 3. Aspartate aminotransferase or alanine aminotransferase \> 1.5 x the upper limit of normal (ULN) or bilirubin \>= 3 mg/dL 4. Serum creatinine \> 1.5 x the ULN 5. Platelets \< 100,000 cells/\[mm\^3\] (10\^9/L), 6. Clinically significant abnormal screening laboratory results as evaluated by the Investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| American College of Rheumatology (ACR) 20 Response Rate at Week 12: ABT-122 Versus Placebo | Week 12 | Percentage of participants with an ACR20 response, defined as at least 20% improvement (compared to baseline values) in tender and swollen joint counts and at least 20% improvement in 3 of the remaining 5 core set measures (subject global assessment of pain, subject global assessment of disease activity, physician global assessment of disease activity, subject assessment of physical function and acute phase reactant high sensitivity C-reactive protein \[hsCRP\]). Estimates of the 95% confidence interval of the response rates for each treatment group were calculated using the Agresti-Coull method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ACR50 Response Rate at Week 12 | Week 12 | Percentage of participants with an ACR50 response, defined as at least 50% improvement (compared to baseline values) in tender and swollen joint counts and at least 50% improvement in 3 of the remaining 5 core set measures (subject global assessment of pain, subject global assessment of disease activity, physician global assessment of disease activity, subject assessment of physical function and acute phase reactant hsCRP. Estimates of the 95% confidence interval of the response rates for each treatment group were calculated using the Agresti-Coull method. |
| ACR70 Response Rate at Week 12 | Week 12 | Percentage of participants with an ACR70 response, defined as at least 70% improvement (compared to baseline values) in tender and swollen joint counts and at least 70% improvement in 3 of the remaining 5 core set measures (subject global assessment of pain, subject global assessment of disease activity, physician global assessment of disease activity, subject assessment of physical function and acute phase reactant hsCRP. Estimates of the 95% confidence interval of the response rates for each treatment group were calculated using the Agresti-Coull method. |
| ACRn at Week 12 | At Week 12 | ACR measures percentage improvements in tender and swollen joint counts, patient assessments of pain, global disease activity and physical function, physician global assessment of disease activity and acute phase reactant. ACRn is a continuous variable based on the ACR criteria. Improvement from baseline in a component of the ACR composite variable was computed as the difference between the baseline value and the value at a given post-baseline visit. A positive value for improvement from baseline for an individual component indicates lesser severity of disease. The 95% confidence interval for mean is constructed using T-statistic with significance level alpha=5%. |
| ACR20 Response Rate at Week 12: ABT-122 Versus Adalimumab | Week 12 | Percentage of participants with an ACR20 response, defined as at least 20% improvement (compared to baseline values) in tender and swollen joint counts and at least 20% improvement in 3 of the remaining 5 core set measures (subject global assessment of pain, subject global assessment of disease activity, physician global assessment of disease activity, subject assessment of physical function and acute phase reactant hsCRP). Estimates of the 95% confidence interval of the response rates for each treatment group were calculated using the Agresti-Coull method. |
| Change From Baseline in Psoriatic Arthritis Disease Activity Score (PASDAS) at Week 12 | Baseline, Week 12 | PASDAS is a continuous compound disease activity state score determined by the combined values of tender or swollen joint counts, participant-reported outcome and hsCRP lab test. The PASDAS is unitless, with a typical score range between 0 and 10. Smaller values on PASDAS indicate a better condition; a negative change from baseline indicates improvement. |
| Change From Baseline in Psoriasis Target Lesion Score at Week 12 | Baseline, Week 12 | Target lesion score for psoriasis in participants with psoriatic arthritis is calculated by adding the scores of plaque erythema, scaling and thickness. Scores range from 0 (no erythema or evidence of plaque thickness) to 10 (severe erythema and evidence of plaque thickness). |
| Change From Baseline in Disease Activity Score 28 (DAS28[hsCRP]) at Week 12 | Baseline, 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, with higher scores indicating more disease activity. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo EW Double-blind placebo administered EW for 12 weeks | 24 |
| Adalimumab 40 mg EOW Double-blind adalimumab 40 mg administered EOW for 12 weeks | 72 |
| ABT-122 120 mg EW Double-blind ABT-122 120 mg administered EW for 12 weeks | 71 |
| ABT-122 240 mg EW Double-blind ABT-122 240 mg administered EW for 12 weeks | 73 |
| Total | 240 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 | 2 | 1 |
Baseline characteristics
| Characteristic | Placebo EW | Adalimumab 40 mg EOW | ABT-122 120 mg EW | ABT-122 240 mg EW | Total |
|---|---|---|---|---|---|
| Age, Continuous | 47.7 years STANDARD_DEVIATION 13.67 | 50.5 years STANDARD_DEVIATION 12.03 | 51.0 years STANDARD_DEVIATION 12.39 | 47.4 years STANDARD_DEVIATION 13.77 | 49.4 years STANDARD_DEVIATION 12.87 |
| Sex: Female, Male Female | 12 Participants | 33 Participants | 37 Participants | 37 Participants | 119 Participants |
| Sex: Female, Male Male | 12 Participants | 39 Participants | 34 Participants | 36 Participants | 121 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 10 / 24 | 39 / 72 | 33 / 71 | 33 / 73 |
| serious Total, serious adverse events | 1 / 24 | 0 / 72 | 0 / 71 | 1 / 73 |
Outcome results
Primary
American College of Rheumatology (ACR) 20 Response Rate at Week 12: ABT-122 Versus Placebo
Percentage of participants with an ACR20 response, defined as at least 20% improvement (compared to baseline values) in tender and swollen joint counts and at least 20% improvement in 3 of the remaining 5 core set measures (subject global assessment of pain, subject global assessment of disease activity, physician global assessment of disease activity, subject assessment of physical function and acute phase reactant high sensitivity C-reactive protein \[hsCRP\]). Estimates of the 95% confidence interval of the response rates for each treatment group were calculated using the Agresti-Coull method.
Time frame: Week 12
Population: Full Analysis Set: all randomized participants who received at least 1 dose of study drug. Non-responder imputation (NRI): missing responses are imputed as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo EW | American College of Rheumatology (ACR) 20 Response Rate at Week 12: ABT-122 Versus Placebo | 25.0 percentage of participants |
| ABT-122 120 mg EW | American College of Rheumatology (ACR) 20 Response Rate at Week 12: ABT-122 Versus Placebo | 64.8 percentage of participants |
| ABT-122 240 mg EW | American College of Rheumatology (ACR) 20 Response Rate at Week 12: ABT-122 Versus Placebo | 75.3 percentage of participants |
p-value: <0.00195% CI: [17.2, 57.7]Fisher Exact
p-value: <0.00195% CI: [28.1, 67.4]Fisher Exact
Secondary
ACR20 Response Rate at Week 12: ABT-122 Versus Adalimumab
Percentage of participants with an ACR20 response, defined as at least 20% improvement (compared to baseline values) in tender and swollen joint counts and at least 20% improvement in 3 of the remaining 5 core set measures (subject global assessment of pain, subject global assessment of disease activity, physician global assessment of disease activity, subject assessment of physical function and acute phase reactant hsCRP). Estimates of the 95% confidence interval of the response rates for each treatment group were calculated using the Agresti-Coull method.
Time frame: Week 12
Population: Full Analysis Set: all randomized participants who received at least 1 dose of study drug. NRI: missing responses are imputed as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo EW | ACR20 Response Rate at Week 12: ABT-122 Versus Adalimumab | 68.1 percentage of participants |
| ABT-122 120 mg EW | ACR20 Response Rate at Week 12: ABT-122 Versus Adalimumab | 64.8 percentage of participants |
| ABT-122 240 mg EW | ACR20 Response Rate at Week 12: ABT-122 Versus Adalimumab | 75.3 percentage of participants |
p-value: 0.72395% CI: [-18.5, 12.1]Fisher Exact
p-value: 0.21595% CI: [-7.4, 21.6]Fisher Exact
Secondary
ACR50 Response Rate at Week 12
Percentage of participants with an ACR50 response, defined as at least 50% improvement (compared to baseline values) in tender and swollen joint counts and at least 50% improvement in 3 of the remaining 5 core set measures (subject global assessment of pain, subject global assessment of disease activity, physician global assessment of disease activity, subject assessment of physical function and acute phase reactant hsCRP. Estimates of the 95% confidence interval of the response rates for each treatment group were calculated using the Agresti-Coull method.
Time frame: Week 12
Population: Full Analysis Set: all randomized participants who received at least 1 dose of study drug. NRI: missing responses are imputed as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo EW | ACR50 Response Rate at Week 12 | 12.5 percentage of participants |
| ABT-122 120 mg EW | ACR50 Response Rate at Week 12 | 37.5 percentage of participants |
| ABT-122 240 mg EW | ACR50 Response Rate at Week 12 | 36.6 percentage of participants |
| ABT-122 240 mg EW | ACR50 Response Rate at Week 12 | 53.4 percentage of participants |
p-value: 0.02195% CI: [3.9, 39.3]Fisher Exact
p-value: 0.61195% CI: [-16.5, 14.8]Fisher Exact
p-value: <0.00195% CI: [20.1, 55.8]Fisher Exact
p-value: 0.03995% CI: [-0.3, 31.3]Fisher Exact
Secondary
ACR70 Response Rate at Week 12
Percentage of participants with an ACR70 response, defined as at least 70% improvement (compared to baseline values) in tender and swollen joint counts and at least 70% improvement in 3 of the remaining 5 core set measures (subject global assessment of pain, subject global assessment of disease activity, physician global assessment of disease activity, subject assessment of physical function and acute phase reactant hsCRP. Estimates of the 95% confidence interval of the response rates for each treatment group were calculated using the Agresti-Coull method.
Time frame: Week 12
Population: Full Analysis Set: all randomized participants who received at least 1 dose of study drug. NRI: missing responses are imputed as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo EW | ACR70 Response Rate at Week 12 | 4.2 percentage of participants |
| ABT-122 120 mg EW | ACR70 Response Rate at Week 12 | 15.3 percentage of participants |
| ABT-122 240 mg EW | ACR70 Response Rate at Week 12 | 22.5 percentage of participants |
| ABT-122 240 mg EW | ACR70 Response Rate at Week 12 | 31.5 percentage of participants |
p-value: 0.03495% CI: [1.5, 29.7]Fisher Exact
p-value: 0.18595% CI: [-5.8, 19.9]Fisher Exact
p-value: 0.00495% CI: [9.6, 39]Fisher Exact
p-value: 0.01795% CI: [2.3, 29.3]Fisher Exact
Secondary
ACRn at Week 12
ACR measures percentage improvements in tender and swollen joint counts, patient assessments of pain, global disease activity and physical function, physician global assessment of disease activity and acute phase reactant. ACRn is a continuous variable based on the ACR criteria. Improvement from baseline in a component of the ACR composite variable was computed as the difference between the baseline value and the value at a given post-baseline visit. A positive value for improvement from baseline for an individual component indicates lesser severity of disease. The 95% confidence interval for mean is constructed using T-statistic with significance level alpha=5%.
Time frame: At Week 12
Population: Full Analysis Set: all randomized participants who received at least 1 dose of study drug. Last observation carried forward (LOCF): missing responses are imputed by calculation based on the last non-missing post-baseline component values.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo EW | ACRn at Week 12 | -20.3 percentage improvement |
| ABT-122 120 mg EW | ACRn at Week 12 | 38.2 percentage improvement |
| ABT-122 240 mg EW | ACRn at Week 12 | 34.7 percentage improvement |
| ABT-122 240 mg EW | ACRn at Week 12 | 48.6 percentage improvement |
p-value: <0.001Kolmogorov-Smirnov test
p-value: 0.561Kolmogorov-Smirnov test
p-value: <0.001Kolmogorov-Smirnov test
p-value: 0.106Kolmogorov-Smirnov test
Secondary
Change From Baseline in Disease Activity Score 28 (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, with higher scores indicating more disease activity.
Time frame: Baseline, Week 12
Population: Full Analysis Set: all randomized participants who received at least 1 dose of study drug. LOCF: missing responses are imputed by calculation based on the last non-missing post-baseline component values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo EW | Change From Baseline in Disease Activity Score 28 (DAS28[hsCRP]) at Week 12 | -0.89 units on a scale |
| ABT-122 120 mg EW | Change From Baseline in Disease Activity Score 28 (DAS28[hsCRP]) at Week 12 | -1.83 units on a scale |
| ABT-122 240 mg EW | Change From Baseline in Disease Activity Score 28 (DAS28[hsCRP]) at Week 12 | -1.96 units on a scale |
| ABT-122 240 mg EW | Change From Baseline in Disease Activity Score 28 (DAS28[hsCRP]) at Week 12 | -2.28 units on a scale |
p-value: <0.00195% CI: [-1.58, -0.57]ANCOVA
p-value: 0.47995% CI: [-0.48, 0.23]ANCOVA
p-value: <0.00195% CI: [-1.9, -0.89]ANCOVA
p-value: 0.01295% CI: [-0.81, -0.1]ANCOVA
Secondary
Change From Baseline in Psoriasis Target Lesion Score at Week 12
Target lesion score for psoriasis in participants with psoriatic arthritis is calculated by adding the scores of plaque erythema, scaling and thickness. Scores range from 0 (no erythema or evidence of plaque thickness) to 10 (severe erythema and evidence of plaque thickness).
Time frame: Baseline, Week 12
Population: Full Analysis Set: all randomized participants who received at least 1 dose of study drug. LOCF: missing responses are imputed by calculation based on the last non-missing post-baseline component values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo EW | Change From Baseline in Psoriasis Target Lesion Score at Week 12 | -1.81 units on a scale |
| ABT-122 120 mg EW | Change From Baseline in Psoriasis Target Lesion Score at Week 12 | -4.16 units on a scale |
| ABT-122 240 mg EW | Change From Baseline in Psoriasis Target Lesion Score at Week 12 | -4.98 units on a scale |
| ABT-122 240 mg EW | Change From Baseline in Psoriasis Target Lesion Score at Week 12 | -4.53 units on a scale |
p-value: <0.00195% CI: [-4.14, -2.19]ANCOVA
p-value: 0.02195% CI: [-1.51, -0.12]ANCOVA
p-value: <0.00195% CI: [-3.7, -1.75]ANCOVA
p-value: 0.28895% CI: [-1.06, 0.32]ANCOVA
Secondary
Change From Baseline in Psoriatic Arthritis Disease Activity Score (PASDAS) at Week 12
PASDAS is a continuous compound disease activity state score determined by the combined values of tender or swollen joint counts, participant-reported outcome and hsCRP lab test. The PASDAS is unitless, with a typical score range between 0 and 10. Smaller values on PASDAS indicate a better condition; a negative change from baseline indicates improvement.
Time frame: Baseline, Week 12
Population: Full Analysis Set: all randomized participants who received at least 1 dose of study drug. LOCF: missing responses are imputed by calculation based on the last non-missing post-baseline component values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo EW | Change From Baseline in Psoriatic Arthritis Disease Activity Score (PASDAS) at Week 12 | -1.46 units on a scale |
| ABT-122 120 mg EW | Change From Baseline in Psoriatic Arthritis Disease Activity Score (PASDAS) at Week 12 | -2.53 units on a scale |
| ABT-122 240 mg EW | Change From Baseline in Psoriatic Arthritis Disease Activity Score (PASDAS) at Week 12 | -2.62 units on a scale |
| ABT-122 240 mg EW | Change From Baseline in Psoriatic Arthritis Disease Activity Score (PASDAS) at Week 12 | -2.86 units on a scale |
p-value: <0.00195% CI: [-1.81, -0.53]ANCOVA
p-value: 0.69695% CI: [-0.54, 0.36]ANCOVA
p-value: <0.00195% CI: [-2.04, -0.77]ANCOVA
p-value: 0.15195% CI: [-0.77, 0.12]ANCOVA