Study to Evaluate Safety and Effectiveness of Oral Apremilast (CC-10004) in Patients With Moderate to Severe Plaque Psoriasis (ESTEEM 1)

Amgen

Status and phase: Completed; Phase 3

Conditions: Plaque Psoriasis

Treatments: Drug: Topical treatments or phototherapy; Drug: Placebo; Drug: Apremilast

Study type: Interventional

Funder types: Industry

Identifiers

NCT01194219

CC-10004-PSOR-008

Details and patient eligibility

About

This study evaluated the effects of an called apremilast. Apremilast works by lowering some of the chemicals that affect psoriasis and therefore improves the symptoms of psoriasis. The purpose of this study was to test apremilast and compare its effects to placebo (an inactive substance which contains no medicine but is in the same form as the drug). This study was able to test for efficacy (improvement of signs and symptoms) and safety of apremilast in patients with moderate to severe psoriasis.

Enrollment: 844 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Males or females, ≥ 18 years of age at the time of signing the informed consent document

2. Diagnosis of chronic plaque psoriasis for at least 12 months prior to Screening

   a. Have moderate to severe plaque psoriasis at Screening and Baseline

3. Must meet all laboratory criteria

4. Females of childbearing potential (FCBP) must have a negative pregnancy test at Screening and Baseline. FCBP who engage in activity in which conception is possible must use 2 forms of contraception as described by the Study Doctor while on study medication and for at least 28 days after taking the last dose of study medication

5. Male subjects (including those who have had a vasectomy) who engage in activity in which conception is possible must use barrier contraception (latex condom or any nonlatex condom NOT made out of natural [animal] membrane [eg, polyurethane]) while on study medication and for a least 28 days after the last dose of study medication.

Exclusion criteria

1. Other than psoriasis, history of any clinically significant (as determined by the Investigator) or other major uncontrolled disease.

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2. Pregnant or breast feeding

3. History of allergy to any component of the study drug

4. Hepatitis B surface antigen positive at Screening

5. Anti-hepatitis C antibody positive at Screening

6. Active tuberculosis (TB) or a history of incompletely treated TB

7. Clinically significant abnormality on 12-Lead Electrocardiogram (ECG) at Screening

8. Clinically significant abnormal chest x-ray

9. History of positive human immunodeficiency virus (HIV), or have congenital or acquired immunodeficiency

10. Active substance abuse or a history of substance abuse within 6 months prior to Screening

11. Bacterial infections requiring treatment with oral or injectable antibiotics, or significant viral or fungal infections, within 4 weeks of Screening

12. Malignancy or history of malignancy (except for treated [ie, cured] basal cell or squamous cell in situ skin carcinomas and treated [ie, cured] cervical intraepithelial neoplasia [CIN] or carcinoma in situ of the cervix with no evidence of recurrence within the previous 5 years)

13. Psoriasis flare or rebound within 4 weeks prior to Screening

14. Evidence of skin conditions that would interfere with clinical assessments

15. Topical therapy within 2 weeks of randomization

16. Systemic therapy for psoriasis within 4 weeks prior to randomization

17. Use of phototherapy within 4 weeks prior to randomization (ie, Ultraviolet B (UVB), psoralen and ultraviolet A (PUVA)

18. Adalimumab, etanercept, infliximab, or certolizumab pegol within 12 weeks prior to randomization

19. Alefacept, briakinumab, or ustekinumab within 24 weeks prior to randomization

20. Use of any investigational drug within 4 weeks prior to randomization

21. Prolonged sun exposure or use of tanning booths or other ultraviolet (UV) light sources

22. Prior treatment with apremilast

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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844 participants in 3 patient groups, including a placebo group

Apremilast

Active Comparator group

Description:

Subjects initially randomized to apremilast 30 mg twice a day, and who demonstrate a PASI 75 response at Week 32 will be randomized (1 to 1) to either continue to receive apremilast 30 mg ) BID or to receive placebo (until effect is lost). At the time effect is lost, subjects will be treated with apremilast 30 mg twice a day for the duration of their participation in the study.

Treatment:

Drug: Apremilast

Drug: Placebo

Placebo

Placebo Comparator group

Description:

Subjects initially randomized to placebo, are assigned to apremilast 30 mg twice a day beginning at Week 16 for the duration of the subject's participation in the study.

Treatment:

Drug: Apremilast

Drug: Placebo

Apremilast 30 mg

Active Comparator group

Description:

Apremilast 30 mg by mouth (PO) twice a day (BID). Participants initially randomized to apremilast 30 mg BID, and who were able to demonstrate a Psoriasis Area Severity Index (PASI) -75 response at week 32 were randomized (1 to 1) to either apremilast 30 mg BID or oral placebo (until effect is lost). At relapse/loss of response to therapy prior to Week 52 (the time at which 75% improvement in PASI score compared to baseline was lost) or at Week 52, participants were re-treated with apremilast 30 mg BID for the duration of their participation in the study. Non-responders or partial responders (PASI response \<75) received additional topical therapies or phototherapy beginning at Week 32.

Treatment:

Drug: Apremilast

Drug: Topical treatments or phototherapy

Drug: Placebo