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

• Sponsor: Acerta Pharma BV (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02387762
• Collaborator: (none)
• Enrollment: 31
• Locations: 17
• Arms: 2
• Duration (Months): 14
• Patients Per Site: 1.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: acalabrutinib; Drug: Placebo	Phase 2

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2a, 4-Week, Double-Blind, Proof-of-Concept Efficacy and Safety Study of ACP-196 Versus Placebo in Subjects With Active Rheumatoid Arthritis on Background Methotrexate
• Study Start Date: Apr 1, 2015
• Actual Primary Completion Date: May 1, 2016
• Actual Study Completion Date: Jun 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ACP-196 + Methotrexate Oral acalabrutinib 15 mg QD plus a stable dose of methotrexate (MTX) between 7.5 mg and 25 mg per week	Drug: acalabrutinib; Other Names: methotrexate
Placebo Comparator: Placebo + Methotrexate Oral placebo QD plus a stable dose of MTX between 7.5 mg and 25 mg per week	Drug: Placebo; Other Names: methotrexate

Outcome Measures

Primary Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pinnacle Research Group	Anniston	Alabama	United States	36207
2	Achieve Clinical Research	Birmingham	Alabama	United States	35216
3	Advanced Arthritis Care and Research	Scottsdale	Arizona	United States	85258
4	TriWest Research Associates, LLC	El Cajon	California	United States	92020
5	Neuropsychiatric Research Center of Orange County	Orange	California	United States	92868
6	Pacific Arthritis Center Medical Group	Santa Monica	California	United States	93454
7	Inland Rheumatology and Osteoporosis Medical Group, Inc	Upland	California	United States	91786
8	San Marcus Research Clinic, Inc.	Hialeah	Florida	United States	33015
9	Suncoast Clinical Research, Inc.	New Port Richey	Florida	United States	34652
10	Suncoast Clinical Research	New Port Richey	Florida	United States	34652
11	The Arthritis Center	Palm Harbor	Florida	United States	34684-3176
12	Office of George Timothy Kelly, MD	Las Vegas	Nevada	United States	89128
13	PMG Research of Salisbury	Salisbury	North Carolina	United States	28144
14	Health Research of Oklahoma	Oklahoma City	Oklahoma	United States	73103-2433
15	Altoona Center for Clinical Research	Duncansville	Pennsylvania	United States	16635
16	Ramesh C. Gupta, MD	Memphis	Tennessee	United States	38119
17	Clear Lake Regional Medical Center	Webster	Texas	United States	77598

Sponsors and Collaborators

• Acerta Pharma BV

Investigators

• Study Director: Acerta Clinical Trials, Acerta Pharma, LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Acerta Pharma BV
• ClinicalTrials.gov Identifier: NCT02387762
• Other Study ID Numbers: ACE-RA-001
• First Posted: Mar 13, 2015
• Last Update Posted: Apr 2, 2019
• Last Verified: Mar 1, 2019

• Keywords provided by Acerta Pharma BV: Acalabrutinib
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Methotrexate; Acalabrutinib

Study Results

Participant Flow

Arm/Group Title	ACP-196 + Methotrexate	Placebo + Methotrexate
Arm/Group Description	Oral acalabrutinib 15 mg QD plus a stable dose of methotrexate (MTX) between 7.5 mg and 25 mg per week	Oral placebo QD plus a stable dose of MTX between 7.5 mg and 25 mg per week
Period Title: Overall Study
STARTED	16	15
COMPLETED	15	15
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	ACP-196 + Methotrexate	Placebo + Methotrexate	Total
Arm/Group Description	Oral acalabrutinib 15 mg QD plus a stable dose of methotrexate (MTX) between 7.5 mg and 25 mg per week	Oral placebo QD plus a stable dose of MTX between 7.5 mg and 25 mg per week	Total of all reporting groups
Overall Participants	16	15	31
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	10 62.5%	12 80%	22 71%
>=65 years	6 37.5%	3 20%	9 29%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.3 (7.21)	56.8 (7.92)	59.1 (7.78)
Sex: Female, Male (Count of Participants)
Female	14 87.5%	13 86.7%	27 87.1%
Male	2 12.5%	2 13.3%	4 12.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 6.7%	1 3.2%
Native Hawaiian or Other Pacific Islander	0 0%	1 6.7%	1 3.2%
Black or African American	2 12.5%	3 20%	5 16.1%
White	14 87.5%	10 66.7%	24 77.4%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	16 100%	15 100%	31 100%
DAS28-CRP at baseline (Scores on Scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Scores on Scale]	6.29 (1.242)	6.29 (1.220)	6.29 (1.211)
Duration of rheumatoid arthritis since initial diagnosis (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	10.3 (7.52)	7.8 (8.12)	9.1 (7.78)
Methotrexate dosing at baseline (mg/week) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/week]	16.9 (6.49)	17.7 (5.22)	17.3 (5.82)

Outcome Measures

1. Primary Outcome

Title	Disease Activity Score 28-CRP (DAS28-CRP) at Week 4
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	ACP 196 + Methotrexate	Placebo + Methotrexate
Arm/Group Description	Oral acalabrutinib 15 mg QD plus a stable dose of methotrexate (MTX) between 7.5 mg and 25 mg per week	Oral placebo QD plus a stable dose of MTX between 7.5 mg and 25 mg per week
Measure Participants	15	15
Mean (Standard Deviation) [Scores on scale]	5.40 (1.563)	5.05 (1.639)

Adverse Events

Time Frame	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.
Adverse Event Reporting Description	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.
Arm/Group Title	ACP-196 + Methotrexate		Placebo + Methotrexate
Arm/Group Description	Oral acalabrutinib 15 mg QD plus a stable dose of methotrexate (MTX) between 7.5 mg and 25 mg per week		Oral placebo QD plus a stable dose of MTX between 7.5 mg and 25 mg per week
All Cause Mortality
	ACP-196 + Methotrexate		Placebo + Methotrexate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/15 (0%)
Serious Adverse Events
	ACP-196 + Methotrexate		Placebo + Methotrexate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/15 (0%)
Other (Not Including Serious) Adverse Events
	ACP-196 + Methotrexate		Placebo + Methotrexate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/16 (62.5%)		6/15 (40%)
Blood and lymphatic system disorders
Anaemia	2/16 (12.5%)		0/15 (0%)
Leukopenia	1/16 (6.3%)		0/15 (0%)
Thrombocytosis	1/16 (6.3%)		0/15 (0%)
Leukocytosis	0/16 (0%)		0/15 (0%)
Gastrointestinal disorders
Diarrhea	1/16 (6.3%)		1/15 (6.7%)
Nausea	1/16 (6.3%)		1/15 (6.7%)
Vomiting	1/16 (6.3%)		0/15 (0%)
General disorders
Oedema peripheral	1/16 (6.3%)		1/15 (6.7%)
Injury, poisoning and procedural complications
Contusion	1/16 (6.3%)		0/15 (0%)
Clavicle fracture	0/16 (0%)		1/15 (6.7%)
Fall	0/16 (0%)		1/15 (6.7%)
Hip Fracture	0/16 (0%)		1/15 (6.7%)
Investigations
Full Blood Count decreased	1/16 (6.3%)		0/15 (0%)
Blood uric acid increased	0/16 (0%)		1/15 (6.7%)
Metabolism and nutrition disorders
Hypochloraemia	1/16 (6.3%)		0/15 (0%)
Hyponatraemia	1/16 (6.3%)		0/15 (0%)
Musculoskeletal and connective tissue disorders
Intervertebral disc degeneration	1/16 (6.3%)		0/15 (0%)
Musculoskeletal chest pain	1/16 (6.3%)		0/15 (0%)
Rheumatoid arthritis	0/16 (0%)		1/15 (6.7%)
Nervous system disorders
Dizziness	1/16 (6.3%)		0/15 (0%)
Lethargy	0/16 (0%)		1/15 (6.7%)
Somnolence	0/16 (0%)		1/15 (6.7%)
Renal and urinary disorders
Haematuria	1/16 (6.3%)		0/15 (0%)
Respiratory, thoracic and mediastinal disorders
Pharyngeal erythema	0/16 (0%)		1/15 (6.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.