Trial Outcomes & Findings for ACP-196 Versus Placebo in Subjects With Rheumatoid Arthritis on Background Methotrexate (NCT NCT02387762)

Last Updated: 2019-04-02

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

31 participants

Primary outcome timeframe

4 weeks

Results posted on

2019-04-02

Participant Flow

Participant milestones

Participant milestones
Measure	ACP-196 + Methotrexate Oral acalabrutinib 15 mg QD plus a stable dose of methotrexate (MTX) between 7.5 mg and 25 mg per week	Placebo + Methotrexate Oral placebo QD plus a stable dose of MTX between 7.5 mg and 25 mg per week
Overall Study STARTED	16	15
Overall Study COMPLETED	15	15
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	ACP-196 + Methotrexate Oral acalabrutinib 15 mg QD plus a stable dose of methotrexate (MTX) between 7.5 mg and 25 mg per week	Placebo + Methotrexate Oral placebo QD plus a stable dose of MTX between 7.5 mg and 25 mg per week
Overall Study Withdrawal by Subject	1	0

Baseline Characteristics

ACP-196 Versus Placebo in Subjects With Rheumatoid Arthritis on Background Methotrexate

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ACP-196 + Methotrexate n=16 Participants Oral acalabrutinib 15 mg QD plus a stable dose of methotrexate (MTX) between 7.5 mg and 25 mg per week	Placebo + Methotrexate n=15 Participants Oral placebo QD plus a stable dose of MTX between 7.5 mg and 25 mg per week	Total n=31 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	10 Participants n=5 Participants	12 Participants n=7 Participants	22 Participants n=5 Participants
Age, Categorical >=65 years	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Age, Continuous	61.3 years STANDARD_DEVIATION 7.21 • n=5 Participants	56.8 years STANDARD_DEVIATION 7.92 • n=7 Participants	59.1 years STANDARD_DEVIATION 7.78 • n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	13 Participants n=7 Participants	27 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) White	14 Participants n=5 Participants	10 Participants n=7 Participants	24 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	16 participants n=5 Participants	15 participants n=7 Participants	31 participants n=5 Participants
DAS28-CRP at baseline	6.29 Scores on Scale STANDARD_DEVIATION 1.242 • n=5 Participants	6.29 Scores on Scale STANDARD_DEVIATION 1.220 • n=7 Participants	6.29 Scores on Scale STANDARD_DEVIATION 1.211 • n=5 Participants
Duration of rheumatoid arthritis since initial diagnosis	10.3 years STANDARD_DEVIATION 7.52 • n=5 Participants	7.8 years STANDARD_DEVIATION 8.12 • n=7 Participants	9.1 years STANDARD_DEVIATION 7.78 • n=5 Participants
Methotrexate dosing at baseline	16.9 mg/week STANDARD_DEVIATION 6.49 • n=5 Participants	17.7 mg/week STANDARD_DEVIATION 5.22 • n=7 Participants	17.3 mg/week STANDARD_DEVIATION 5.82 • n=5 Participants

PRIMARY outcome

Timeframe: 4 weeks

Population: Intent-to-treat population, which included all randomized subjects

Outcome measures

Outcome measures
Measure	ACP 196 + Methotrexate n=15 Participants Oral acalabrutinib 15 mg QD plus a stable dose of methotrexate (MTX) between 7.5 mg and 25 mg per week	Placebo + Methotrexate n=15 Participants Oral placebo QD plus a stable dose of MTX between 7.5 mg and 25 mg per week
Disease Activity Score 28-CRP (DAS28-CRP) at Week 4	5.40 Scores on scale Standard Deviation 1.563	5.05 Scores on scale Standard Deviation 1.639

Adverse Events

ACP-196 + Methotrexate

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Placebo + Methotrexate

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Ahmed Hamdy, MD, VP of Early Development

Acerta Pharma

Phone: 650-591-2800

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Site and PI can publish/publicly present the results of the study only with prior written consent of Sponsor or otherwise after expiry of 12 months following completion of the study. Site and PI agree to provide 45 days written notice to Sponsor prior to submission for publication or presentation.
Publication restrictions are in place

Restriction type: OTHER

Measure	ACP-196 + Methotrexate n=16 participants at risk Oral acalabrutinib 15 mg QD plus a stable dose of methotrexate (MTX) between 7.5 mg and 25 mg per week	Placebo + Methotrexate n=15 participants at risk Oral placebo QD plus a stable dose of MTX between 7.5 mg and 25 mg per week
Blood and lymphatic system disorders Anaemia	12.5% 2/16 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	0.00% 0/15 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Blood and lymphatic system disorders Leukopenia	6.2% 1/16 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	0.00% 0/15 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Blood and lymphatic system disorders Thrombocytosis	6.2% 1/16 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	0.00% 0/15 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Blood and lymphatic system disorders Leukocytosis	0.00% 0/16 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	0.00% 0/15 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Gastrointestinal disorders Diarrhea	6.2% 1/16 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	6.7% 1/15 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Gastrointestinal disorders Nausea	6.2% 1/16 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	6.7% 1/15 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Gastrointestinal disorders Vomiting	6.2% 1/16 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	0.00% 0/15 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
General disorders Oedema peripheral	6.2% 1/16 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	6.7% 1/15 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Injury, poisoning and procedural complications Contusion	6.2% 1/16 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	0.00% 0/15 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Injury, poisoning and procedural complications Clavicle fracture	0.00% 0/16 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	6.7% 1/15 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Injury, poisoning and procedural complications Fall	0.00% 0/16 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	6.7% 1/15 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Injury, poisoning and procedural complications Hip Fracture	0.00% 0/16 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	6.7% 1/15 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Investigations Full Blood Count decreased	6.2% 1/16 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	0.00% 0/15 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Investigations Blood uric acid increased	0.00% 0/16 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	6.7% 1/15 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Metabolism and nutrition disorders Hypochloraemia	6.2% 1/16 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	0.00% 0/15 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Metabolism and nutrition disorders Hyponatraemia	6.2% 1/16 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	0.00% 0/15 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Musculoskeletal and connective tissue disorders Intervertebral disc degeneration	6.2% 1/16 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	0.00% 0/15 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	6.2% 1/16 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	0.00% 0/15 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	0.00% 0/16 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	6.7% 1/15 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Nervous system disorders Dizziness	6.2% 1/16 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	0.00% 0/15 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Nervous system disorders Lethargy	0.00% 0/16 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	6.7% 1/15 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Nervous system disorders Somnolence	0.00% 0/16 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	6.7% 1/15 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Renal and urinary disorders Haematuria	6.2% 1/16 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	0.00% 0/15 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Respiratory, thoracic and mediastinal disorders Pharyngeal erythema	0.00% 0/16 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	6.7% 1/15 • From the date of the first dose of study drug up to 30 days after the date of the last dose of study drug, up to 6 months. Subjects with multiple events for a given system organ class (SOC) and preferred term (PT) were counted only once for each SOC and PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.