Rheumatoid Arthritis
Conditions
Keywords
Acalabrutinib
Brief summary
This study is evaluating the safety, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy of ACP-196 in subjects with Rheumatoid Arthritis on background Methotrexate.
Detailed description
A multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial. The on-treatment period is 4 weeks with weekly visits to the clinic, followed by a 4-week safety follow-up period after the last dose of ACP-196/placebo. The study was to evaluate the safety, PK, PD, and efficacy of ACP-196 in subjects with Rheumatoid Arthritis on background Methotrexate
Interventions
DRUGacalabrutinib
DRUGPlacebo
Sponsors
Acerta Pharma BV
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 75 Years
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: * Diagnosis of RA according to the 2010 ACR/EULAR Classification Criteria . * Must be on a stable MTX dose (7.5 to 25 mg/week) * Subjects must be able to read and understand the consent form, complete the study-related procedures, and communicate with the study staff. * Are willing and able to adhere to the study visit schedule, and understand and comply with other protocol requirements. Main
Exclusion criteria
* Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease free for ≥ 5 years. * A life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of ACP-196, or put the study outcomes at undue risk. * Subjects who have taken any investigational drug within the previous 30 days before randomization. * Use of all other synthetic disease-modifying antirheumatic drugs (DMARDS) such as but not limited to leflunomide, azathioprine, cyclosporine, penicillamine or gold salts within 8 weeks of randomization. * Use of etanercept, anakinra, tofacitinib within 4 weeks of randomization. * Use of abatacept, humira, infliximab, or tocilizumab within 8 weeks of randomization.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease Activity Score 28-CRP (DAS28-CRP) at Week 4 | 4 weeks | Disease activity score 28 - C-reactive protein (DAS28-CRP) is a score to measure disease activity in patients with rheumatoid arthritis by aggregating data of 28 joints, and is calculated by the scores on scale using the following variables: The number of swollen and tender joints, CRP level, and patient's global assessment of disease activity. The total score of the DAS28 values may range from 2.0 to 10.0 while higher values mean a higher disease activity. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ACP-196 + Methotrexate Oral acalabrutinib 15 mg QD plus a stable dose of methotrexate (MTX) between 7.5 mg and 25 mg per week | 16 |
| Placebo + Methotrexate Oral placebo QD plus a stable dose of MTX between 7.5 mg and 25 mg per week | 15 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo + Methotrexate | ACP-196 + Methotrexate | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 6 Participants | 9 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 10 Participants | 22 Participants |
| Age, Continuous | 56.8 years STANDARD_DEVIATION 7.92 | 61.3 years STANDARD_DEVIATION 7.21 | 59.1 years STANDARD_DEVIATION 7.78 |
| DAS28-CRP at baseline | 6.29 Scores on Scale STANDARD_DEVIATION 1.22 | 6.29 Scores on Scale STANDARD_DEVIATION 1.242 | 6.29 Scores on Scale STANDARD_DEVIATION 1.211 |
| Duration of rheumatoid arthritis since initial diagnosis | 7.8 years STANDARD_DEVIATION 8.12 | 10.3 years STANDARD_DEVIATION 7.52 | 9.1 years STANDARD_DEVIATION 7.78 |
| Methotrexate dosing at baseline | 17.7 mg/week STANDARD_DEVIATION 5.22 | 16.9 mg/week STANDARD_DEVIATION 6.49 | 17.3 mg/week STANDARD_DEVIATION 5.82 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 14 Participants | 24 Participants |
| Region of Enrollment United States | 15 participants | 16 participants | 31 participants |
| Sex: Female, Male Female | 13 Participants | 14 Participants | 27 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 15 |
| other Total, other adverse events | 10 / 16 | 6 / 15 |
| serious Total, serious adverse events | 0 / 16 | 0 / 15 |
Outcome results
Primary
Disease Activity Score 28-CRP (DAS28-CRP) at Week 4
Disease activity score 28 - C-reactive protein (DAS28-CRP) is a score to measure disease activity in patients with rheumatoid arthritis by aggregating data of 28 joints, and is calculated by the scores on scale using the following variables: The number of swollen and tender joints, CRP level, and patient's global assessment of disease activity. The total score of the DAS28 values may range from 2.0 to 10.0 while higher values mean a higher disease activity.
Time frame: 4 weeks
Population: Intent-to-treat population, which included all randomized subjects
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ACP 196 + Methotrexate | Disease Activity Score 28-CRP (DAS28-CRP) at Week 4 | 5.40 Scores on scale | Standard Deviation 1.563 |
| Placebo + Methotrexate | Disease Activity Score 28-CRP (DAS28-CRP) at Week 4 | 5.05 Scores on scale | Standard Deviation 1.639 |