Apremilast as a Direct Treatment for Mild-to-moderate Plaque Psoriasis Versus Placebo: an Analysis of Clinical Safety and Efficacy (ADVANCE)
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT03721172 |
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Recruitment Status :
Completed
First Posted : October 26, 2018
Results First Posted : May 17, 2021
Last Update Posted : May 17, 2021
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This is a Phase 3, multicenter, randomized, placebo-controlled, double-blind study designed to evaluate the efficacy and safety of apremilast (CC-10004) in subjects with mild to moderate plaque psoriasis.
Approximately 574 subjects with mild to moderate plaque psoriasis will be randomized 1:1 to receive either apremilast 30 mg BID or placebo for the first 16 weeks.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Psoriasis | Drug: Apremilast Other: Placebo | Phase 3 |
The study will consist of four phases:
- Screening Phase - up to 35 days
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Double-blind Placebo-controlled Phase - Weeks 0 to 16
- Subjects will be randomly assigned to either apremilast 30 mg tablets orally BID or placebo tablets (identical in appearance to apremilast 30 mg tablets) orally BID.
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Apremilast Extension Phase - Weeks 16 to 32
- All subjects will be switched to (or continue with) apremilast 30 mg BID. All subjects will maintain this dosing through Week 32.
- Observational Follow-up Phase - 4 weeks - Four-week Post-Treatment Observational Follow-up Phase for all subjects who complete the study or discontinue the study early.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 595 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 3, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study of the Efficacy and Safety of Apremilast (CC-10004) in Subjects With Mild to Moderate Plaque Psoriasis |
| Actual Study Start Date : | March 11, 2019 |
| Actual Primary Completion Date : | March 6, 2020 |
| Actual Study Completion Date : | July 24, 2020 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Placebo-controlled Phase:
Participants received placebo as oral tablets twice daily (BID) for up to 16 weeks (Week 0 to Week 16).
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Other: Placebo
Placebo, oral, twice daily |
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Experimental: Placebo-controlled Phase: Apremilast 30 mg
Participants received apremilast 30 mg as oral tablets BID for up to 16 weeks (Week 0 to Week 16).
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Drug: Apremilast
Apremilast, oral, twice daily |
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Experimental: Extension Phase: Apremilast 30 mg
Eligible participants who completed the placebocontrolled phase entered the extension phase and received apremilast 30 mg as oral tablets BID for up to an additional 16 weeks (Week 16 to Week 32).
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Drug: Apremilast
Apremilast, oral, twice daily |
- Percentage of Participants With a Static Physician Global Assessment (sPGA) Response at Week 16 During the Placebo-Controlled Phase [ Time Frame: Baseline and Week 16 of the placebo-controlled phase ]
The sPGA is a 5-point scale where 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate, and 4 =severe. Scores incorporate an assessment by the Investigator of the severity of the 3 primary signs of the disease: erythema, scaling and plaque elevation.
An sPGA response is defined as sPGA score of clear (0) or almost clear (1) and with at least a 2-point reduction from baseline at Week 16.
- Percentage of Participants With a ≥ 75 Percent (%) Improvement From Baseline in Affected Body Surface Area (BSA) at Week 16 [ Time Frame: Baseline and Week 16 of the placebo-controlled phase ]The BSA is a measurement of involved skin over the whole body. The overall BSA affected by psoriasis is estimated based on the palm area of the participant's hand. The surface area of the whole body is made up of approximately 100 palms or "handprints" (each entire palmar surface or "handprint" equates to approximately 1% of total body surface area).
- Change From Baseline in Percentage of Affected BSA at Week 16 [ Time Frame: Baseline and Week 16 of the placebo-controlled phase ]
The BSA is a measurement of involved skin over the whole body. The overall BSA affected by psoriasis is estimated based on the palm area of the participant's hand. The surface area of the whole body is made up of approximately 100 palms or "handprints" (each entire palmar surface or "handprint" equates to approximately 1% of total body surface area).
A negative change from baseline indicates a reduction of affected BSA.
- Change From Baseline in Total Psoriasis Area Severity Index (PASI) Score at Week 16 [ Time Frame: Baseline and Week 16 of the placebo-controlled phase ]
The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) is multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. These values for each anatomic region are summed to yield the PASI score.
PASI scores range from 0 to 72, with higher scores reflecting greater disease severity.
A negative change from baseline indicates an improvement of disease symptoms.
- Percentage of Participants Who Achieved BSA ≤ 3% for Participants With Baseline Affected BSA > 3% at Week 16 [ Time Frame: Baseline and Week 16 of the placebo-controlled phase ]The BSA is a measurement of involved skin over the whole body. The overall BSA affected by psoriasis is estimated based on the palm area of the participant's hand. The surface area of the whole body is made up of approximately 100 palms or "handprints" (each entire palmar surface or "handprint" equates to approximately 1% of total body surface area).
- Percentage of Participants With ≥ 4-point Reduction From Baseline in Whole Body Itch Numeric Rating Scale (NRS) Score at Week 16 Who Had Baseline Whole Body Itch NRS ≥ 4 [ Time Frame: Baseline and Week 16 of the placebo-controlled phase ]The whole body itch NRS is a self-reported measure where participants were asked to assess whole body itch and select a number on a scale of 0-10, where 0 represents no itch, and 10 represents the worst imaginable itch. A reduction in score from baseline represents an improvement in symptoms.
- Percentage of Participants With a Scalp Physician Global Assessment (ScPGA) Response at Week 16 Among Participants With Baseline scPGA Score ≥ 2 at Week 16 [ Time Frame: Baseline and Week 16 of the placebo-controlled phase ]
The ScPGA is a 5-point scale ranging from 0 (clear) to 4 (severe), incorporating an Investigator's assessment of the severity of the three primary signs of the disease: erythema, scaling and plaque elevation of the overall scalp.
An ScPGA response is defined as and ScPGA score clear (0) or almost clear (1) with at least a 2-point reduction from baseline among participants with a baseline ScPGA score ≥ 2.
- Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score at Week 16 [ Time Frame: Baseline and Week 16 of the placebo-controlled phase ]
The DLQI is a 10 item questionnaire dealing with the participant's skin. With the exception of Item Number 7, the participant responds on a four-point scale, ranging from 0 (not at all) to 3 (very much). Item Number 7 is a multi-part item, the first part of which ascertains whether the participant's skin prevented them from working or studying (Yes or No), and if "No," then the subject is asked how much of a problem the skin has been at work or study over the past week, with response alternatives being 0 (not at all), 1 (a little) and 2 (a lot).
Total scores have a possible range of 0 to 30, with 30 corresponding to the worst health-related quality of life, and 0 corresponding to the best score.
A negative change from baseline indicates an improvement in health-related quality of life scores.
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) ]
An adverse event (AE) is An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. A TEAE is any AE that occurs following administration of study treatment.
Frequency of TEAEs was assessed as well as severity and treatment relatedness.
A TEAE was considered severe based on the Investigator's assessment. A TEAE could be severe if it was serious or non-serious, had symptoms causing discomfort or pain, requiring medical or surgical attention or intervention, interfered with activities of daily life and if drug therapy was required.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Subjects must satisfy the following criteria to be enrolled in the study:
- Subject must be male or female, ≥18 years of age at the time of signing the informed consent form (ICF).
- Subject must have a diagnosis of chronic plaque psoriasis for at least 6 months prior to signing the ICF.
- Subject must have a diagnosis of mild to moderate plaque psoriasis at both Screening and Baseline.
- Subject must be inadequately controlled with or intolerant of at least one topical therapy at both Screening and Baseline.
- Subject must be in good health (except for psoriasis) as judged by the investigator, based on medical history, physical examination, clinical laboratories, and urinalysis.
- Subject must meet laboratory criteria.
- Subject has not had prior exposure to biologics for the treatment of psoriatic arthritis or psoriasis, or any other condition that could impact the assessment of psoriasis.
Exclusion Criteria:
The presence of any of the following will exclude a subject from enrollment:
- Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
- Subjects has 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.
2. Subject has hepatitis B surface antigen positive at Screening. 3. Subject has active tuberculosis (TB) or a history of incompletely treated TB.
4. Subject has history of positive human immunodeficiency virus (HIV), or has congenital or acquired immunodeficiency (eg, common variable immunodeficiency disease).
5. Subject has hepatitis B surface antigen or anti-hepatitis C antibody positive at Screening.
6. Subject has prior history of suicide attempt at any time in the subject's life time or major psychiatric illness requiring hospitalization within the last 3 years prior to signing the informed consent. 7. Subject has current or planned concurrent use of therapies that may have a possible effect on psoriasis during the course of the treatment phase of the trial.
8. Use of any investigational drug beginning 4 weeks prior to randomization, or 5 pharmacokinetic/pharmacodynamic half-lives, if known (whichever is longer).
9. Subject had prior treatment with apremilast.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03721172
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| Study Director: | MD | Amgen |
Documents provided by Amgen:
| Responsible Party: | Amgen |
| ClinicalTrials.gov Identifier: | NCT03721172 |
| Other Study ID Numbers: |
CC-10004-PSOR-022 U1111-1218-8372 ( Registry Identifier: WHO ) |
| First Posted: | October 26, 2018 Key Record Dates |
| Results First Posted: | May 17, 2021 |
| Last Update Posted: | May 17, 2021 |
| Last Verified: | April 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Informed Consent Form (ICF) Clinical Study Report (CSR) |
| Time Frame: | Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study. |
| Access Criteria: | Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below. |
| URL: | http://www.amgen.com/datasharing |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Phase 3 Double-Blind Efficacy Safety Apremilast Otezla CC-10004 |
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