Phase II Study of Apremilast (CC-10004) in Adults With in Psoriatic Arthritis

Amgen

Status and phase: Completed; Phase 2

Conditions: Psoriatic Arthritis

Treatments: Drug: Apremilast; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT00456092

CC-10004-PSA-001

Details and patient eligibility

About

This study is to look at the preliminary efficacy and safety of 2 dose regimens of apremilast (20 mg twice a day and 40 mg once a day) versus placebo in patients with active psoriatic arthritis.

Full description

Prior to the implementation of Amendment 1/UK3 the study consisted of 3 phases - pre-randomization up to 35 days, up to 84 days placebo-controlled treatment and a 28-day observational follow up. After the implementation of Amendment 1/UK3, the study consisted of 4 phases - pre-randomization up to 35 days, up to 84 days treatment in the placebo controlled treatment phase, up to 84 days treatment in the active treatment extension phase and a 28 day follow up. Participants who completed the treatment phase prior to implementation of amendment 1/UK3 did not have the option of entering the extension phase.

Enrollment: 204 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of psoriatic arthritis (Moll and Wright Criteria), including symmetrical or asymmetrical peripheral joint involvement for at least 6 months

• Active psoriatic arthritis at the time of screening and baseline as defined by: 3 or more swollen joints AND 3 or more tender joints

• Negative rheumatoid factor (RF)

• If using methotrexate, be on methotrexate for at least 168 days (24 weeks) and be on a stable dose for at least 56 days prior to screening and throughout the study

• If using oral corticosteroids, be on a stable dose of prednisone ≤ 10 mg/day or equivalent for at least 28 days prior to screening and throughout the study

• If using nonsteroidal anti-inflammatory drug (NSAID) therapy, be on a stable dose for at least 14 days prior to screening and throughout the study

• Must meet the following laboratory criteria:

  • Hemoglobin ≥ 9 g/dL
  • Hematocrit ≥ 27%
  • White blood cell (WBC) count ≥ 3000/μL (≥ 3.0 X 10^9/L) and < 20,000/μL (< 20 X 10^9/L)
  • Neutrophils ≥ 1500 /μL (≥ 1.5 X 10^9/L)
  • Platelets ≥ 100,000 /μL (≥ 100 X 10^9/L)
  • Serum creatinine ≤ 1.5 mg/dL (≤ 132.6 μmol/L)
  • Total bilirubin ≤ 2.0 mg/dL
  • Aspartate transaminase (AST [serum glutamic oxaloacetic transaminase, SGOT]) and alanine transaminase (ALT [serum glutamate pyruvic transaminase, SGPT]) ≤ 1.5x upper limit of normal (ULN)

• Females of childbearing potential (FCBP) must have a negative urine pregnancy test at screening (Visit 1). In addition, sexually active FCBP must agree to use TWO adequate forms of contraception while on study medication. A FCBP must agree to have pregnancy tests every 28 days while on study medication

• Males (including those who have had a vasectomy) must agree to use barrier contraception (latex condoms) when engaging in reproductive sexual activity with FCBP while on study medication and for at least 84 days after taking the last dose of study medication

Exclusion criteria

History of any clinically significant cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, immunologic, or other major diseases

• Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
• Pregnant or lactating female
• History of active Mycobacterium tuberculosis infection (any subspecies) within 3 years prior to the screening visit. Infections that occurred > 3 years prior to entry must have been effectively treated.
• History of incompletely treated latent Mycobacterium tuberculosis infection (as indicated by a positive Purified Protein Derivative [PPD] skin test or in vitro test [T SPOT®.TB, QuantiFERON Gold®])
• Clinically significant abnormality on the chest x-ray (CXR) at screening
• Current erythrodermic, guttate, or pustular forms of psoriasis
• History of infected joint prosthesis within the past 5 years
• Systemic therapy for psoriasis and/or psoriatic arthritis (except for methotrexate, ≤ 10 mg/day prednisone or equivalent, and NSAIDs) including, but not limited to, sulfasalazine, leflunomide, chloroquine, hydroxychloroquine, gold compounds, parenteral corticosteroids (including intra-articular), penicillamine, cyclosporine, oral retinoids, mycophenolate mofetil, thioguanine, hydroxyurea, sirolimus, tacrolimus, azathioprine, and fumaric acid esters within 28 days of randomization and throughout the study
• Topical therapy for the treatment of psoriasis including, but not limited to topical steroids, topical vitamin A or D analog preparations, tacrolimus, pimecrolimus, or anthralin within 14 days of randomization (Note: Topical background therapy for treatment of psoriasis is allowed, except within 24 hours of a study visit, as follows: mild or moderate potency corticosteroids for treatment of the palms, face, scalp, axillae, plantar surfaces, and groin in accordance with the manufacturer's suggested usage. Nonmedicated emollients [eg, Eucerin®] and tar shampoo are also allowed.)
• Phototherapy (ultraviolet light A [UVA], narrow-band ultraviolet light B [NB-UVB], psoralens and long-wave ultraviolet radiation [PUVA]) within 28 days prior to randomization
• Etanercept use within 56 days prior to randomization
• Adalimumab, efalizumab, or infliximab use within 84 days prior to randomization
• Alefacept use within 168 days (24 weeks) prior to randomization
• Use of intra-articular corticosteroids within 28 days prior to randomization
• Use of any investigational medication within 28 days prior to randomization or 5 half-lives if known (whichever is longer)
• Any clinically significant abnormality on 12-lead electrocardiogram (ECG) at screening
• High-risk factor(s) for, or a history of, human immunodeficiency virus (HIV), hepatitis B, or hepatitis C virus infection
• History of malignancy within previous 5 years (except for treated basal-cell skin carcinoma(s) and/or fewer than 3 treated squamous-cell skin carcinomas)
• Evidence of skin conditions at the time of screening visit that would interfere with evaluations of the effect of study medication on psoriasis

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

204 participants in 3 patient groups, including a placebo group

Apremilast 40 mg QD

Experimental group

Description:

Participants received 40 mg apremilast orally once a day (QD) for 12 weeks in the Treatment Phase. Participants who entered the Extension Phase continued to receive 40 mg apremilast QD for an additional 12 weeks. The dose of apremilast was titrated starting at 10 mg QD during Days 1 to 3 followed by 20 mg QD during Days 4 to 7 and then 40 mg QD thereafter. A single dose reduction to 20 mg per day was allowed for participants who experienced intolerable adverse effects from study medication.

Treatment:

Drug: Apremilast

Apremilast 20 mg BID

Experimental group

Description:

Participants received 20 mg apremilast orally twice a day (BID) for 12 weeks in the Treatment Phase. Participants who entered the Extension Phase continued to receive 20 mg apremilast BID for an additional 12 weeks. The dose of apremilast was titrated starting at 10 mg QD during Days 1 to 3 followed by 20 mg QD during Days 4 to 7 and then 20 mg BID thereafter. A single dose reduction to 20 mg per day was allowed for participants who experienced intolerable adverse effects from study medication.

Treatment:

Drug: Apremilast

Placebo

Placebo Comparator group

Description:

Participants received matching placebo to apremilast orally BID for 12 weeks during the Treatment Phase. Participants who entered the Extension Phase were re-randomized on Day 85 to receive either 40 mg apremilast QD or 20 mg apremilast BID for 12 weeks.

Treatment:

Drug: Placebo