Study of Apremilast to Evaluate the Safety and Effectiveness for Patients With Rheumatoid Arthritis

NCT01285310 | Terminated Phase 2 Results DMC

• 2 other identifiers: CC-10004-RA-0022010-019926-15
• Study Type: interventional
• Target: 237
• Locations: 4 countries
• Sites: 50

Brief Summary

The purpose of this study is to determine whether Apremilast is safe and effective in the treatment of patients with rheumatoid arthritis, specifically in improving signs and symptoms of rheumatoid arthritis (tender and swollen joints, pain, physical function and structure) in treated patients who have had an inadequate response to Methotrexate.

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid, Arthritis

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With an American College of Rheumatology 20% Improvement (ACR 20) Response at Week 16

  Percentage of participants with an American College of Rheumatology 20% Improvement (ACR 20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: * ≥ 20% improvement in 68 tender joint count; * ≥ 20% improvement in 66 swollen joint count; and * ≥ 20% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (\[HAQ-DI\]); C-Reactive Protein.

  Baseline and Week 16

Secondary Outcomes (72)

• Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 16

  Baseline and Week 16

• Percentage of Participants With an American College of Rheumatology 20% Improvement (ACR 20) Response at Week 24

  Baseline and Week 24

• Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 24

  Baseline and Week 24

• Change From Baseline in the Medical Outcome Study Short Form 36-item (SF-36) Physical Functioning Domain at Week 16

  Baseline and Week 16

• Change From Baseline in the Clinical Disease Activity Index (CDAI) at Week 16

  Baseline and Week 16

Study Arms (3)

Apremilast 30 mg

EXPERIMENTAL

Drug: Apremilast 30 mg

Apremilast 20 mg

EXPERIMENTAL

Drug: Apremilast 20 mg; Drug: Placebo

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Apremilast 30 mg DRUG

30 mg oral Apremilast tablets administered twice daily (BID) for 24 weeks during the placebo-controlled phase followed by 30mg Apremilast tablets administered BID for up to 1.5 years in the active treatment / active treatment extension phase.

Also known as: CC-10004

Apremilast 30 mg

Apremilast 20 mg DRUG

20 mg oral Apremilast tablets administered twice daily (BID) for 24 weeks during the placebo-controlled phase followed by 20mg Apremilast tablets administered BID for up to 1.5 years in the active treatment / active treatment extension phase.

Apremilast 20 mg

Placebo DRUG

Oral Placebo tablets administered twice daily (BID) for 24 weeks during the placebo-controlled phase followed by 20mg Apremilast tablets administered BID for up to 1.5 years in active treatment / active treatment extension phase. Participants who are nonresponders will advance early to 20 mg Apremilast BID at Week 16.

Apremilast 20 mg; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must have a documented diagnosis of Rheumatoid Arthritis (1987 American College of Rheumatology Criteria) with onset of signs/symptoms of disease ≥ 4 months of duration from randomization.
• Must be receiving treatment on an outpatient basis.
• Must have active disease despite current methotrexate treatment as defined below:
• ≥ 6 swollen joints (66 swollen joint count) AND
• ≥ 6 tender joints (68 tender joint count)
• Must meet at least one of the four lab requirements below:
• High Sensitivity C-Reactive Protein (hsCRP) ≥ 10 mg/L
• Erythrocyte Sedimentation Rate (ESR) \> 28 mm after the first 1 hour
• Positive for Rheumatoid Factor (RF)
• Positive for Anti-cyclic Citrullinated Peptide (anti-CCP) antibodies
• For participants participating in the Magnetic Resonance Imaging (MRI) assessment:
• Must have Rheumatoid Arthritis joint involvement, as assessed by swollen joint counts in: 1) at least two Metacarpophalangeal (MCP) swollen joints on the same hand, or 2) at least one swollen Metacarpophalangeal (MCP) joint and swollen wrist on the same hand.
• Must have been treated with methotrexate for at least 4 months prior to randomization, and must be on stable dose. Participants will be required to maintain their stable dose through Week 52 of the study. Oral folate (folic acid) supplementation is required with a minimum dose of 5 mg/week, or instead leucovorin may be used up to 10 mg/week orally.
• Non-steroidal anti-inflammatory drugs (NSAIDs) and pain medications are allowed, however, must be on stable regimen for at least 7 days prior to randomization and through Week 52 of the study.
• Oral corticosteroids (if taken) are allowed, however, must be on stable dose of prednisone ≤ 10 mg/day or equivalent for at least 28 days prior to randomization and through Week 52 of the study.

You may not qualify if:

• Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization.
• Rheumatic autoimmune disease other than Rheumatoid Arthritis, including systemic lupus erythematosus, mixed connective tissue disease, scleroderma, polymyositis or significant systemic involvement secondary to Rheumatoid Arthritis (eg, vasculitis, pulmonary fibrosis or Felty syndrome). Sjögren syndrome secondary to Rheumatoid Arthritis is allowable.
• Functional Class IV as defined by the American College of Rheumatology (ACR) Classification of Functional Status in Rheumatoid Arthritis.
• Prior history of, or current, inflammatory joint disease other than Rheumatoid Arthritis (eg, gout, reactive arthritis, psoriatic arthritis, ankylosing spondylitis, Lyme disease).
• Receiving treatment with Disease-modifying antirheumatic drugs (DMARDs) (other than methotrexate), including biologic Disease-modifying antirheumatic drugs (DMARDs)Previous use is only allowed after adequate washout prior to randomization.
• Inadequate response to treatment with an anti-tumor necrosis factor (anti-TNF) agent. Patients who terminated previous anti-tumor necrosis factor (anti-TNF) treatment due to cost or safety reason, such as discomfort with the subcutaneous injections, may participate in this study after adequate washout.
• Treatment with any investigational agent within four weeks (or five half-lives of the investigational drug, whichever is longer) of screening.
• Previous treatment with any cell depleting therapies, including investigational agents.
• Treatment with intravenous gamma globulin, plasmapheresis or Prosorba® column within 6 months of baseline.
• Intra-articular or parenteral corticosteroids are not allowed within 6 weeks prior to randomization.
• Any previous treatment with alkylating agents such as cyclophosphamide or chlorambucil, or with total lymphoid irradiation.
• Pregnant women or nursing (breast feeding) mothers.
• Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including severe or very severe chronic obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus as defined by Hemoglobin A1c \> 9.0%) or gastrointestinal (GI) disease.
• Uncontrolled disease states, such as asthma, psoriasis or inflammatory bowel disease, where flares are commonly treated with oral or parenteral corticosteroids.
• Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections (including but not limited to tuberculosis and atypical mycobacterial disease, Hepatitis B and C, and herpes zoster, but excluding onychomycosis) or any major episode of infection requiring hospitalization or treatment with IV or oral antibiotics within 4 weeks of screening.

Sponsors & Collaborators

• Amgen: lead

Study Sites (50)

ArthroCare, Arthritis Care Research

Gilbert, Arizona, 85234, United States

Location

Arizona Research Center

Phoenix, Arizona, 85023, United States

Location

TriWest Research Associates

La Mesa, California, 91942, United States

Location

Desert Medical Advances

Palm Desert, California, 92260, United States

Location

Stanford University Medical Center

Palo Alto, California, 94304, United States

Location

Med Investigations/Sierra

Roseville, California, 95661, United States

Location

Inland Rheumatology Clinical Trials, Inc.

Upland, California, 91786, United States

Location

Denver Arthritis Clinic

Denver, Colorado, 80230, United States

Location

In Vivo Clinical Research

Doral, Florida, 33166, United States

Location

San Marcus Research Clinic

Miami, Florida, 33015, United States

Location

Advanced Pharma CR, LLC

Miami, Florida, 33175, United States

Location

Jeffrey Alper, MD Research

Naples, Florida, 34102, United States

Location

Suncoast Clinical Research

New Port Richey, Florida, 34652, United States

Location

Tampa Medical Group, PA

Tampa, Florida, 33614, United States

Location

Alastair Kennedy, MD

Vero Beach, Florida, 32962, United States

Location

LaPorte County Institute for Clinical Research, Inc.

Michigan City, Indiana, 46360, United States

Location

Associated Internal Medicine Specialists, PC

Battle Creek, Michigan, 49015, United States

Location

Saint Paul Rheumatology

Eagan, Minnesota, 55121, United States

Location

Physician's East

Greenville, North Carolina, 27834, United States

Location

David R. Mandel, M.D., Inc.

Mayfield, Ohio, 44143, United States

Location

Health Research of Oklahoma

Oklahoma City, Oklahoma, 73103, United States

Location

Altoona Center for Clinical Research

Duncansville, Pennsylvania, 16635, United States

Location

Austin Regional Clinic

Austin, Texas, 78759, United States

Location

Metroplex Research Center

Dallas, Texas, 75231, United States

Location

Modern Research Associates

Dallas, Texas, 75231, United States

Location

Sun Research Institute

San Antonio, Texas, 78215, United States

Location

Stone Oak Rheumatology

San Antonio, Texas, 78232, United States

Location

Center for Excellence in Aging and Geriatric Health

Williamsburg, Virginia, 23185, United States

Location

Arthritis Northwest, Rheumatology

Spokane, Washington, 99204, United States

Location

Revmatologie s.r.o.

Brno, 638 00, Czechia

Location

L.K.N. Arthrocentrum s.r.o.

Hlučín, 748 01, Czechia

Location

ARTMEDI UPD s.r.o.

Hostivice, 253 01, Czechia

Location

Revmatologicky ustav

Prague, 128 50, Czechia

Location

Revmatologicka ambulance

Prague, 140 00, Czechia

Location

Fakultni Thomayerova nemocnice s poliklinikou

Prague, 140 59, Czechia

Location

PV - MEDICAL, s.r.o.

Zlín, 760 01, Czechia

Location

NZOZ Osteo-Medic s.c. Artur Racewicz, Jerzy Supronik

Bialystok, 15-351, Poland

Location

NZOZ Centrum Osteoporozy i Chorob Kostno-Stawowych

Bialystok, 15-461, Poland

Location

Szpital Uniwersytecki nr 2 im. Dr Jana Biziela w Bydgoszczy

Bydgoszcz, 85-168, Poland

Location

Centrum Kliniczno-Badawcze

Elblag, 82-300, Poland

Location

Centrum Leczenia Chorob Cywilizacyjnych

Gdynia, 81-384, Poland

Location

Centrum Leczenia Chorob Cywilizacyjnych

Katowice, 40-478, Poland

Location

Malopolskie Centrum Medyczne (408)

Krakow, 30-552, Poland

Location

Niepubliczny Zaklad Opieki Zdrowotnej REUMED

Lublin, 20-607, Poland

Location

Prywatna Praktyka Lekarska Pawel Hrycaj

Poznan, 61-397, Poland

Location

Centrum Leczenia Chorob Cywilizacyjnych

Warsaw, 02-777, Poland

Location

Hospital Universitario a Coruña

A Coruña, 15006, Spain

Location

Hospital Universitario de Canarias

San Cristóbal de La Laguna, 38320, Spain

Location

Hospital Clinico Universitario de Santiago

Santiago de Compostela, 15706, Spain

Location

Hospital Sierrallana

Torrelavega, 39300, Spain

Location

Related Publications (1)

• Genovese MC, Jarosova K, Cieslak D, Alper J, Kivitz A, Hough DR, Maes P, Pineda L, Chen M, Zaidi F. Apremilast in Patients With Active Rheumatoid Arthritis: A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study. Arthritis Rheumatol. 2015 Jul;67(7):1703-10. doi: 10.1002/art.39120.

  PMID: 25779750 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

apremilast

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Limitations and Caveats

The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.

Results Point of Contact

• Title: Anne McClain
• Organization: Celgene Corporation

clinicaltrialdisclosure@celgene.com

888-260-1599

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2010
• First Posted: January 28, 2011
• Study Start: December 9, 2010
• Primary Completion: February 21, 2012
• Study Completion: September 10, 2012
• Last Updated: May 8, 2020
• Results First Posted: August 15, 2014

Record last verified: 2020-04

Locations

ES (4); US (29); CZ (7); PL (10)