Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid Arthritis
Brief summary
A Phase 2b, open-label extension (OLE) study in rheumatoid arthritis (RA) patients designed to collect long-term safety, tolerability, efficacy, and immunogenicity data of the proposed new adalimumab formulation.
Detailed description
All participants who completed Study NCT01712178 had an opportunity to enroll into the study and to receive the new adalimumab formulation at a dose of 40 mg every other week (eow) for an additional 24 weeks.
Interventions
BIOLOGICALNew formulation adalimumab
New formulation adalimumab 40 mg every other week
Sponsors
AbbVie (prior sponsor, Abbott)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subject has completed the preceding Study M13-390 for rheumatoid arthritis and has not developed any discontinuation criteria from that study. 2. If female, subject is either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy and/or hysterectomy) or is of childbearing potential and is practicing an approved method of birth control throughout the study and for 150 days after last dose of study drug. Examples of approved methods of birth control include the following (see local informed consent for more detail): * Condoms, sponge, foams, jellies, diaphragm or intrauterine device (IUD); * Hormonal contraceptives for 90 days prior to study drug administration; * A vasectomized partner. 3. Subjects must be able and willing to self-administer subcutaneous (SC) injections or have a qualified person available to administer SC injections. 4. Subject is judged to be in good general health as determined by the Principal Investigator based upon the results of medical history, physical examination, laboratory profile performed at Baseline. 5. Subjects must be able and willing to provide written informed consent and to comply with the requirements of this study protocol.
Exclusion criteria
1. Ongoing infections at Week 0 that have NOT been successfully treated. Subjects with ongoing infections undergoing treatment may be enrolled BUT NOT dosed until the infection has been successfully treated. 2. Subject currently uses or plans to use anti-retroviral therapy at any time during the study. 3. Subject plans to use any live vaccine during the study. 4. Positive pregnancy test at Baseline (Week 0). 5. Subject is considered by the investigator, for any reason, to be an unsuitable candidate for the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Disease Activity Score 28 (DAS28) at Weeks 36 and 48 | Baseline (Study NCT01712178 Week 0 Visit), Weeks 36 and 48 | The Disease Activity Score (DAS28) is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, C-reactive protein, and general health are included in the DAS28 score. Scores on the DAS28 range from 0 to 10. A DAS28 score \>5.1 indicates high disease activity, a DAS28 score \<3.2 indicates low disease activity, and a DAS28 score \<2.6 indicates clinical remission. |
| Percentage of Participants With an American College of Rheumatology (ACR) 20 Response at Weeks 36 and 48 | Baseline (Study NCT01712178 Week 0 Visit), Weeks 36 and 48 | American College of Rheumatology 20% (ACR20) response. A participant is a responder if the following 3 criteria for improvement from baseline are met: * ≥ 20% improvement in tender joint count; * ≥ 20% improvement in swollen joint count; and * ≥ 20% improvement in at least 3 of the 5 following parameters: * Physician global assessment of disease activity * Patient global assessment of disease activity * Patient assessment of pain * Disability Index of the Health Assessment * CRP (Acute phase reactant (Erythrocyte sedimentation rate/C-reactive protein)) |
| Percentage of Participants With an American College of Rheumatology (ACR) 50 Response at Weeks 36 and 48 | Baseline (Study NCT01712178 Week 0 Visit), Weeks 36 and 48 | American College of Rheumatology 50% (ACR50) response. A participant is a responder if the following 3 criteria for improvement from baseline are met: * ≥ 50% improvement in tender joint count; * ≥ 50% improvement in swollen joint count; and * ≥ 50% improvement in at least 3 of the 5 following parameters: * Physician global assessment of disease activity * Patient global assessment of disease activity * Patient assessment of pain * Disability Index of the Health Assessment * CRP (Acute phase reactant (Erythrocyte sedimentation rate/C-reactive protein)) |
| Mean Change From Baseline in Health Assessment Questionnaire (HAQ-DI) at Weeks 36 and 48 | Baseline (Study NCT01712178 Week 0 Visit), Weeks 36 and 48 | The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a patient-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. The minimal clinically important difference (MCID) defined for the HAQ-DI is 0.22. HAQ remission indicating normal physical function is defined by HAQ-DI \< 0.5. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Positive for Anti-adalimumab Antibody | Week 24 through Week 48 | Percentage of participants with anti-adalimumab antibody |
Countries
Belgium, Czechia, Germany, Puerto Rico, Romania, Slovakia, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| New Formulation for 48 Weeks New formulation of adalimumab 40 mg every other week for 24 weeks in Study NCT01712178, followed by 24 weeks of treatment with the new formulation of adalimumab 40 mg every other week | 44 |
| Current Formulation for 24 Weeks, New Formulation for 24 Weeks Current formulation of adalimumab 40 mg every other week for 24 weeks in Study NCT01712178, followed by 24 weeks of treatment with the new formulation of adalimumab 40 mg every other week | 44 |
| Total | 88 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lack of Efficacy | 0 | 2 |
| Overall Study | Withdrew Consent | 0 | 2 |
Baseline characteristics
| Characteristic | New Formulation for 48 Weeks | Current Formulation for 24 Weeks, New Formulation for 24 Weeks | Total |
|---|---|---|---|
| Age, Continuous | 55.7 years STANDARD_DEVIATION 10.8 | 52.0 years STANDARD_DEVIATION 12 | 53.9 years STANDARD_DEVIATION 11.5 |
| Sex: Female, Male Female | 37 Participants | 37 Participants | 74 Participants |
| Sex: Female, Male Male | 7 Participants | 7 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 18 / 44 | 19 / 44 |
| serious Total, serious adverse events | 2 / 44 | 1 / 44 |
Outcome results
Primary
Mean Change From Baseline in Disease Activity Score 28 (DAS28) at Weeks 36 and 48
The Disease Activity Score (DAS28) is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, C-reactive protein, and general health are included in the DAS28 score. Scores on the DAS28 range from 0 to 10. A DAS28 score \>5.1 indicates high disease activity, a DAS28 score \<3.2 indicates low disease activity, and a DAS28 score \<2.6 indicates clinical remission.
Time frame: Baseline (Study NCT01712178 Week 0 Visit), Weeks 36 and 48
Population: All available data were included. If a participant did not have a value for a given time of evaluation, but did have a value at times previous to this after the study drug treatment began, the last available value was used to replace the missing value.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| New Formulation for 48 Weeks | Mean Change From Baseline in Disease Activity Score 28 (DAS28) at Weeks 36 and 48 | Week 36 | -2.4 units on a scale | Standard Deviation 1.17 |
| New Formulation for 48 Weeks | Mean Change From Baseline in Disease Activity Score 28 (DAS28) at Weeks 36 and 48 | Week 48 | -2.4 units on a scale | Standard Deviation 1.29 |
| Current Formulation for 24 Weeks, New Formulation for 24 Weeks | Mean Change From Baseline in Disease Activity Score 28 (DAS28) at Weeks 36 and 48 | Week 36 | -2.2 units on a scale | Standard Deviation 1.05 |
| Current Formulation for 24 Weeks, New Formulation for 24 Weeks | Mean Change From Baseline in Disease Activity Score 28 (DAS28) at Weeks 36 and 48 | Week 48 | -2.2 units on a scale | Standard Deviation 1.28 |
Primary
Mean Change From Baseline in Health Assessment Questionnaire (HAQ-DI) at Weeks 36 and 48
The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a patient-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. The minimal clinically important difference (MCID) defined for the HAQ-DI is 0.22. HAQ remission indicating normal physical function is defined by HAQ-DI \< 0.5.
Time frame: Baseline (Study NCT01712178 Week 0 Visit), Weeks 36 and 48
Population: Data from participants receiving the new formulation of adalimumab in Study NCT01712178 were analyzed for 44 and 43 participants, respectively, at weeks 36 and 48. Data for the participants receiving the current formulation of adalimumab in Study NCT01712178 were analyzed for 43 participants at week 36 and 40 participants at week 48.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| New Formulation for 48 Weeks | Mean Change From Baseline in Health Assessment Questionnaire (HAQ-DI) at Weeks 36 and 48 | Week 36 | -0.5 units on a scale | Standard Deviation 0.6 |
| New Formulation for 48 Weeks | Mean Change From Baseline in Health Assessment Questionnaire (HAQ-DI) at Weeks 36 and 48 | Week 48 | -0.5 units on a scale | Standard Deviation 0.57 |
| Current Formulation for 24 Weeks, New Formulation for 24 Weeks | Mean Change From Baseline in Health Assessment Questionnaire (HAQ-DI) at Weeks 36 and 48 | Week 36 | -0.5 units on a scale | Standard Deviation 0.69 |
| Current Formulation for 24 Weeks, New Formulation for 24 Weeks | Mean Change From Baseline in Health Assessment Questionnaire (HAQ-DI) at Weeks 36 and 48 | Week 48 | -0.5 units on a scale | Standard Deviation 0.58 |
Primary
Percentage of Participants With an American College of Rheumatology (ACR) 20 Response at Weeks 36 and 48
American College of Rheumatology 20% (ACR20) response. A participant is a responder if the following 3 criteria for improvement from baseline are met: * ≥ 20% improvement in tender joint count; * ≥ 20% improvement in swollen joint count; and * ≥ 20% improvement in at least 3 of the 5 following parameters: * Physician global assessment of disease activity * Patient global assessment of disease activity * Patient assessment of pain * Disability Index of the Health Assessment * CRP (Acute phase reactant (Erythrocyte sedimentation rate/C-reactive protein))
Time frame: Baseline (Study NCT01712178 Week 0 Visit), Weeks 36 and 48
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| New Formulation for 48 Weeks | Percentage of Participants With an American College of Rheumatology (ACR) 20 Response at Weeks 36 and 48 | Week 36 | 72.7 percentage of participants |
| New Formulation for 48 Weeks | Percentage of Participants With an American College of Rheumatology (ACR) 20 Response at Weeks 36 and 48 | Week 48 | 74.4 percentage of participants |
| Current Formulation for 24 Weeks, New Formulation for 24 Weeks | Percentage of Participants With an American College of Rheumatology (ACR) 20 Response at Weeks 36 and 48 | Week 36 | 76.7 percentage of participants |
| Current Formulation for 24 Weeks, New Formulation for 24 Weeks | Percentage of Participants With an American College of Rheumatology (ACR) 20 Response at Weeks 36 and 48 | Week 48 | 80.0 percentage of participants |
Primary
Percentage of Participants With an American College of Rheumatology (ACR) 50 Response at Weeks 36 and 48
American College of Rheumatology 50% (ACR50) response. A participant is a responder if the following 3 criteria for improvement from baseline are met: * ≥ 50% improvement in tender joint count; * ≥ 50% improvement in swollen joint count; and * ≥ 50% improvement in at least 3 of the 5 following parameters: * Physician global assessment of disease activity * Patient global assessment of disease activity * Patient assessment of pain * Disability Index of the Health Assessment * CRP (Acute phase reactant (Erythrocyte sedimentation rate/C-reactive protein))
Time frame: Baseline (Study NCT01712178 Week 0 Visit), Weeks 36 and 48
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| New Formulation for 48 Weeks | Percentage of Participants With an American College of Rheumatology (ACR) 50 Response at Weeks 36 and 48 | Week 36 | 50.0 percentage of participants |
| New Formulation for 48 Weeks | Percentage of Participants With an American College of Rheumatology (ACR) 50 Response at Weeks 36 and 48 | Week 48 | 53.5 percentage of participants |
| Current Formulation for 24 Weeks, New Formulation for 24 Weeks | Percentage of Participants With an American College of Rheumatology (ACR) 50 Response at Weeks 36 and 48 | Week 36 | 51.2 percentage of participants |
| Current Formulation for 24 Weeks, New Formulation for 24 Weeks | Percentage of Participants With an American College of Rheumatology (ACR) 50 Response at Weeks 36 and 48 | Week 48 | 57.5 percentage of participants |
Secondary
Percentage of Participants Positive for Anti-adalimumab Antibody
Percentage of participants with anti-adalimumab antibody
Time frame: Week 24 through Week 48
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| New Formulation for 48 Weeks | Percentage of Participants Positive for Anti-adalimumab Antibody | 13.6 percentage of participants |
| Current Formulation for 24 Weeks, New Formulation for 24 Weeks | Percentage of Participants Positive for Anti-adalimumab Antibody | 18.2 percentage of participants |