Primary Objective- To evaluate the clinical efficacy and safety of oral apremilast (APR) 30 mg twice a day (BID) compared with placebo, in subjects with moderate to severe plaque psoriasis at Week 16.Secondary Objectives- To evaluate the clinical…
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Proportion of subjects with either apremilast 30 mg BID or placebo who achieve
at least a 75% reduction in PASI (PASI-75) at Week 16 from baseline.
Secondary outcome
- Proportion of subjects with an sPGA score of clear (0) or almost clear (1)
with at least 2 points reduction at Week 16
- Percent change from baseline in the affected body surface area (BSA %) at
Week 16
- Proportion of subjects who achieve PASI-50 at Week 16
- Change from baseline in DLQI total score at Week 16
- Change from baseline in Mental Component Summary (MCS) score of SF-36 at Week
16
- Proportion of subjects with an LS-PGA score of clear (0) or almost clear (1)
at Week 16
Background summary
Psoriasis is a chronic disease that requires long-term treatment, ideally with
effective agents that offer convenient dosing and a low incidence of adverse
events. Currently available systemic therapies are limited by risks of hepatic,
renal and neurological toxicities, teratogenicity, as well
as an increased risk of infections and malignancies. Etanercept is the most
widely used biologic for psoriasis (Decision Resources- Psoriasis, 2011). Like
other biologics, etanercept is administered parenterally. Given the limitations
of current systemic psoriasis treatments, there is an unmet medical need for an
effective oral agent that is well tolerated and less immunosuppressive than the
current oral agents and parenteral biologics.
Apremilast (CC-10004) is a specific phosphodiesterase type 4 (PDE4) inhibitor
under development for use in the treatment of inflammatory conditions. PDE4 is
one of the major phosphodiesterases expressed in leukocytes. Inhibitors of PDE4
cause accumulation of
intracellular cyclic adenosine monophosphate (cAMP), resulting in inhibition of
proinflammatory cytokine transcription and other cellular responses, such as
neutrophil degranulation and chemotaxis.
In completed Phase 2 studies in subjects with psoriasis and psoriatic
arthritis, apremilast has demonstrated broad anti-inflammatory and
immunomodulatory activity, as well as efficacy in psoriasis and psoriatic
arthritis. Based on preclinical and clinical data to date, apremilast is
expected to have a more favorable safety profile than the currently available
systemic psoriasis treatments, while delivering efficacy with convenient oral
dosing.
Study objective
Primary Objective
- To evaluate the clinical efficacy and safety of oral apremilast (APR) 30 mg
twice a day (BID) compared with placebo, in subjects with moderate to severe
plaque psoriasis at Week 16.
Secondary Objectives
- To evaluate the clinical efficacy and safety of etanercept 50 mg subcutaneous
(SC) once weekly (QW) compared with placebo, in subjects with moderate to
severe plaque psoriasis at Week 16.
- To evaluate the relative safety of a crossover from etanercept 50 mg
subcutaneous (SC) once weekly to apremilast 30 mg BID, as compared with
apremilast dosed since Week 0 in subjects with moderate to severe plaque
psoriasis after Week 16.
- Explore relative safety/tolerability of subjects starting apremilast therapy
without the 7 day dose titration.
Study design
This is a phase 3b, multicenter, randomized, placebo-controlled, double-blind,
double-dummy study of the efficacy and safety of apremilast (CC-10004),
etanercept, and placebo in subjects with moderate to severe plaque psoriasis.
Approximately 240 subjects will be randomized 1:1:1 to the three treatment
groups. Subject randomization for treatment assignments will be stratified
according to their calculated body mass index (BMI) categories at Screening
(BMI < 30 or BMI * 30). All subjects will receive both tablets and injections
through Week 16:
- Subjects randomized to the apremilast treatment group will receive apremilast
30 mg tablets orally twice daily and evaluator/subject-blinded SC saline
(placebo) injections once weekly for 16 weeks
- Subjects randomized to the etanercept treatment group will receive placebo
tablets (identical in appearance to apremilast 30 mg tablets) orally twice
daily and etanercept as two SC 25 mg injections (50 mg total dose) once weekly
for 16 weeks
- Subjects randomized to the placebo treatment group will receive placebo
tablets (identical in appearance to apremilast 30 mg tablets) orally twice
daily and evaluator/subject-blinded SC saline (placebo) injections once weekly
for 16 weeks
The study will consist of four phases:
*Screening Phase * up to 35 days
* Double-blind Placebo-controlled Phase * Weeks 0-16
Subjects will receive treatment with one of the following:
- apremilast 30 mg tablets orally BID plus once weekly saline (placebo)
injections (1 mL x 2 injections SC), or
- etanercept 50 mg SC QW plus placebo tablets orally BID, or
- placebo tablets and evaluator/subject-blinded SC saline (placebo) injections.
Subjects will take oral tablets (either 30 mg APR or placebo) BID and receive
two SC injections (either etanercept 25 mg each dose or saline placebo) QW.
* Apremilast Extension Phase * Weeks 16-104
- All subjects will be switched to (or continue with) 30 mg BID apremilast at
Week 16. All subjects will maintain this dosing through Week 104.
- Starting at Week 32, all non-responders (< PASI-50) will have the option of
adding topical therapies (including, but not limited to, topical
corticosteroids, retinoids or vitamin D analog preparations) and/or
phototherapy (excluding oral PUVA) to their treatment regimen.
* Post-treatment Observational Follow-up Phase
- Four-week Post-treatment Observational Follow-up Phase for all subjects who
complete the study or discontinue from the study early.
Study burden and risks
In completed Phase 2 studies in subjects with psoriasis and psoriatic
arthritis, apremilast has demonstrated broad anti-inflammatory and
immunomodulatory activity, as well as efficacy in psoriasis and psoriatic
arthritis. Based on preclinical and clinical data to date, apremilast is
expected to have a more favorable safety profile than the currently available
systemic psoriasis treatments, while delivering efficacy with convenient oral
dosing.
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Age
Inclusion criteria
1. Males or females, * 18 years of age at the time of signing the informed consent document.
2. Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted.
3. Able to adhere to the study visit schedule and other protocol requirements.
4. Diagnosis of chronic plaque psoriasis for at least 12 months prior to Screening.
5. Have moderate to severe plaque psoriasis at Screening and Baseline as defined by
a. PASI score * 12 and
b. BSA * 10%, and
c. sPGA * 3 (moderate)
Exclusion criteria
1.Other than psoriasis, history of any clinically significant cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, immunologic disease, or other major uncontrolled disease.
2.Any condition, including the presence of laboratory abnormalities, which would place the subject at unacceptable risk if he/she were to participate in the study.
3.Any condition, including other inflammatory diseases or dermatologic conditions, that confound the ability to interpret data from the study.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2012-000859-14-NL |
| ClinicalTrials.gov | NCT01690299 |
| CCMO | NL42206.091.12 |