Phase 3 study to evaluate safety and effectiveness of oral Apremilast (CC-10004) in patients with Psoriatic Arthritis who have not been previously treated with disease-modifiying antirheumatic drugs

• Register: EUCTR
• Last refreshed on: 2 October 2017
• Main ID: EUCTR2010-020324-22-EE
• Date of registration: 20/04/2012
• Prospective Registration: Yes
• Primary sponsor: Celgene Corporation
• Public title: Phase 3 study to evaluate safety and effectiveness of oral Apremilast (CC-10004) in patients with Psoriatic Arthritis who have not been previously treated with disease-modifiying antirheumatic drugs
• Scientific title: A Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group, efficacy and safety study of two doses of Apremilast (CC-10004) in subjects with active psoriatic arthritis who have not been previously treated with disease-modifying antirheumatic drugs
• Date of first enrolment: 21/05/2012
• Target sample size: 495
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-020324-22
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Bulgaria, Canada, Czech Republic, Denmark, Estonia, France, Germany, Hungary, Italy, Korea, Republic of, Lithuania, New Zealand, Poland, Romania, Russian Federation, South Africa, Spain, Taiwan, United Kingdom, United States

Contacts

• Name: Clinical Trial Disclosure
• Affiliation: Celgene Corporation

• Name: Clinical Trial Disclosure
• Affiliation: Celgene Corporation

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female, aged = 18 years at time of consent.
2. Must 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. Have a documented diagnosis of PsA (by any criteria) of = 3 months’ duration.
5. Meet the CASPAR criteria for PsA at time of screening.
6. Have = 3 swollen AND = 3 tender joints.
7. Have not been previously treated with DMARDS (small molecules or biologics)
8. Be receiving treatment on an outpatient basis.
9. If taking oral corticosteroids, must be on a stable dose of prednisone = 10 mg/day or equivalent for at least 1 month prior to screening.
10. If taking NSAIDs or narcotic analgesics, must be on stable dose for at least 2 weeks prior to screening and until they have completed the Week 16 study visit.
11. Low potency topical corticosteroids (Appendix M or locally-available equivalent) will be allowed as background therapy for treatment of psoriasis on the face, axillae and groin in accordance with the
manufacturers’ suggested usage during the course of the study. Subjects with scalp psoriasis will be permitted to use coal tar shampoo and/or salicylic acid scalp preparations on scalp lesions. A non-medicated skin emollient (eg, Eucerin cream) will also be permitted for body lesions only. Subjects must not use these treatments within
24 hours prior to the clinic visit.
12. Meet the following laboratory criteria:
- White blood cell count = 3000/mm3 (= 3.0 x 10^9/L) and < 14,000/mm3
(< 14 x 10^9/L)
- Platelet count =100,000/mm3 (= 100 x 10^9/L)
- Serum creatinine = 1.5 mg/dL (= 132.6 µmol/L)
- AST (SGOT) and ALT (SGPT) = 2 X upper limit of normal (ULN)
- Total bilirubin = 2 mg/dL (= 34 µmol/L)
- Hemoglobin = 9 g/dL (= 5.6 mmol/L)
- Hemoglobin A1c = 9.0%
13. Male subjects (including those who have had a vasectomy) who engage in activity in which conception is possible must use barrier contraception (male latex condom or any nonlatex condom NOT made out of natural [animal] membrane [for example, polyurethane]) while on investigational product and for at least 28 days after the last dose of investigational product.
14. Females of childbearing potential (FCBP) must have a negative pregnancy test at Screening and Baseline. While on investigational product and for at least 28 days after taking the last dose of investigational product, FCBP who engage in activity in which conception is possible must use one of the approved contraceptive† options described below:
Option 1: Any one of the following highly effective methods: hormonal contraception (oral, injection, implant, transdermal patch, vaginal ring); intrauterine device (IUD); tubal ligation; or partner's vasectomy;
OR
Option 2: Male or female condom (latex condom or nonlatex condom NOT made out of natural [animal] membrane [for example, polyurethane]); PLUS one additional barrier method: (a) diaphragm with spermicide; (b) cervical cap with spermicide; or (c) contraceptive sponge with spermicide.

Note: The protocol language regarding contraception has been revised. As this study is fully enrolled, the updated language regarding contraception is included in Section 6.2 (Contraception Education) of this amendment.

† The female subject’s chosen form of contraception must be effective by the time the female subject is randomized into the study (for example, hormonal contraception should be in
Exclusion criteria:
1. History of clinically significant (as determined by the Investigator) cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, immunologic disease, or other major uncontrolled disease.
2. Any condition, including the presence of laboratory abnormalities that 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.
3. Clinically significant abnormality on 12-lead ECG at Screening.
4. Pregnant or breast feeding.
5. History of allergy to any component of the investigational product (IP).
6. Hepatitis B surface antigen positive at screening.
7. Hepatitis C antibody positive at screening.
8. AST (SGOT) and/or ALT (SGPT) > 1.5X ULN and total bilirubin > ULN or albumin < lower limit of normal (LLN).
9. History of positive Human Immunodeficiency Virus (HIV), or congenital or acquired immunodeficiency (eg, Common Variable Immunodeficiency Disease).
10. Active tuberculosis or a history of incompletely treated tuberculosis.
11. Clinically significant abnormality based upon chest radiograph with at least PA view (radiograph must be taken within 12 weeks prior to Screening or during the Screening visit). An additional lateral view is strongly recommended but not required.
12. Active substance abuse or a history of substance abuse within 6 months prior to Screening.
13. Bacterial infections requiring treatment with oral or injectable antibiotics, or significant viral or fungal infections, within 4 weeks of Screening. Any treatment for such infections must have been completed at least 4 weeks prior to Screening.
14. 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).
15. Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization.
16. Erythrodermic, guttate, or generalized pustular psoriasis.
17. Topical therapy for psoriasis, except as noted in the Inclusion Criteria, within 2 weeks of randomization (including but not limited to topical corticosteroids, topical retinoids or vitamin D analog preparations, tacrolimus, pimecrolimus, or anthralin).
18. Rheumatic autoimmune disease other than PsA, including systemic lupus erythematosis (SLE), mixed connective tissue disease (MCTD), scleroderma, polymyositis or fibromyalgia.
19. Functional Class IV as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis (Appendix Q).
20. Prior history of or current inflammatory joint disease other than PsA (eg, gout, reactive arthritis, RA, ankylosing spondylitis, Lyme disease).
21. Prior use of disease-modifying antirheumatic drugs (DMARDS; small molecules or biologics)
22. Use of the following systemic therapy(ies) within 4 weeks of randomization, including but not limited to corticosteroids (except as noted in inclusion criteria), oral retinoids and fumaric acid esters.
23. Use of phototherapy within 4 weeks of randomization (ie, UVB, PUVA).
24. Previous treatment with any cell depleting therapies, including investigational agents (eg, rituximab, CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19, and anti-CD20).
25. Treatment with intravenous gamma globulin, plasmapheresis, or Prosorba® column within 6 months of baseline.
26. Any previous treatment with alk

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Psoriatic arthritis, an inflammatory arthritis that occurs in 6-39% of psoriasis patients
MedDRA version: 20.0 Level: LLT Classification code 10037160 Term: Psoriatic arthritis System Organ Class: 100000004859

Intervention(s)

Product Name: Apremilast
Product Code: CC-10004
Pharmaceutical Form: Tablet
INN or Proposed INN: Apremilast
CAS Number: 608141-41-9
Current Sponsor code: CC-10004
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: Apremilast
Product Code: CC-10004
Pharmaceutical Form: Tablet
INN or Proposed INN: Apremilast
CAS Number: 608141-41-9
Current Sponsor code: CC-10004
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: Apremilast
Product Code: CC-10004
Pharmaceutical Form: Tablet
INN or Proposed INN: Apremilast
CAS Number: 608141-41-9
Current Sponsor code: CC-10004
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 30-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: To evaluate the following in subjects with active PsA who are treated with apremilast or placebo for up to 24
weeks:
- safety and tolerability
- efficacy
- physical function
- fatigue
- clinical disease activity

To evaluate the following in subjects with active PsA who are treated with apremilast for up to 52 weeks:
- safety and tolerability
- efficacy
- physical function
- fatigue
- clinical disease activity

To evaluate the efficacy, safety, and tolerability of 2 doses of apremilast for up to 5 years' administration to
subjects with active PsA

Timepoint(s) of evaluation of this end point: 16 weeks' treatment

Main Objective: The primary objective of the study is to evaluate the clinical efficacy of 2 doses of apremilast (20 mg or 30 mg orally BID) compared with placebo, on the signs and symptoms of psoriatic arthritis (PsA) after 16 weeks'
administration

Primary end point(s): Proportion of subjects in each treatment group who achieve the American College of Rheumatology criteria for a 20% improvement (ACR 20), compared with baseline

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: See E.5.2

Secondary end point(s): Safety of up to 5 years’ administration as defined by:
- Type, frequency, severity, and relationship of adverse events to apremilast
- Number of subjects who prematurely discontinue study medication due to any adverse event
- Frequency of clinically significant changes in physical examination, vital signs, electrocardiogram, and/or laboratory findings

Efficacy at Week 16 (after 16 weeks of treatment):
- Change from baseline in physical function (Health Assessment Questionnaire-Disability Index [HAQ-DI])
- Change from baseline in the physical function domain score of the Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36)
- Proportion of subjects who achieve the modified Psoriatic Arthritis Response Criteria (PsARC)
- Change from baseline in subject’s assessment of pain (VAS)
- Change from baseline in the Maastricht Ankylosing Spondylitis Entheses Score (MASES) in subjects with pre-existing enthesopathy
- Change from baseline in the dactylitis severity score in subjects with pre-existing dactylitis
- Change from baseline in the Clinical Disease Activity Index (CDAI)
- Change from baseline in the Disease Activity Score (DAS28)
- Change from baseline in the Functional Assessment of Chronic Illness Therapy –Fatigue (FACIT-Fatigue) score
- Proportion of subjects with pre-existing enthesopathy whose MASES improves by = 20%
- Proportion of subjects with pre-existing dactylitis whose dactylitis severity score improves by = 1
- Proportion of subjects with a good or moderate European League Against Rheumatism (EULAR) response
- Proportion of subjects who achieve an ACR 50, compared with baseline
- Proportion of subjects who achieve an ACR 70, compared with baseline
- Proportion of subjects with pre-existing enthesopathy whose MASES improves to 0
- Proportion of subjects with pre-existing dactylitis whose dactylitis severity score improves to 0

Efficacy at Week 24 (after 24 weeks of treatment):
- Proportion of subjects who achieve the ACR 20, compared with baseline
- Change from baseline in physical function (HAQ-DI)
- Change from baseline in the physical function domain score of the SF-36
- Proportion of subjects who achieve the modified PsARC
- Change from baseline in subject’s assessment of pain (VAS)
- Change from baseline in the MASES in subjects with pre-existing enthesopathy
- Change from baseline in the dactylitis severity score in subjects with pre-existing dactylitis
- Change from baseline in the CDAI
- Change from baseline in the DAS28
- Change from baseline in the FACIT-Fatigue score
- Proportion of subjects with pre-existing enthesopathy whose MASES improves by = 20%
- Proportion of subjects with pre-existing dactylitis whose dactylitis severity score improves by = 1
- Proportion of subjects with a good or moderate EULAR response
- Proportion of subjects who achieve an ACR 50, compared with baseline
- Proportion of subjects who achieve an ACR 70, compared with baseline
- Proportion of subjects with pre-existing enthesopathy whose MASES improves to 0
- Proportion of subjects with pre-existing dactylitis whose dactylitis severity score improves to 0

Efficacy at Week 52 (after 52 weeks of treatment):
- Proportion of subjects who achieve the ACR 20, compared with baseline
- Change from baseline in physical function (HAQ-DI)
- Change from baseline in the physical function domain score of the SF-36
- Proportion of subjects who achieve the modified PsARC
- Change from baseline in subject’s assessment of pain (VAS)
- Change from baseline in the MASES in subjects with pre-existing enthesopathy
- Change from baseline in the dactylitis severity score subjects with pre-existing dactylitis
- Change from baseline in the CDAI
- Change from baseline in the DAS28
- Change from baseline in the FACIT-Fatigue score
- Proportion of subjects with pre-existing enthesopathy whose MASES improves by = 20%
- Proportion of subjects with pre-existing dactylitis whose dactylitis severity score improves by = 1
- Proportion of subjects with a good or moderate EULAR response
- Proportion of subjects who achieve an ACR 50, compared with baseline
- Proportion of subjects who achieve an ACR 70, compared with baseline
- Proportion of subjects with pre-existing enthesopathy whose MASES improves to 0
- Proportion of subjects with pre-existing dactylitis whose dactylitis severity score improves to 0

Secondary ID(s)

2010-020324-22-GB

CC-10004-PSA-005

Source(s) of Monetary Support

Celgene Corporation