Apremilast 30 mg Twice Daily (BID) Combined With Dupilumab

Apremilast 30 mg BID Combined With Dupilumab for the Treatment of Recalcitrant Moderate-to-Severe Atopic Dermatitis

Open label phase 2 investigational study of efficacy and safety of apremilast 30 mg twice a day (BID) in chronic atopic dermatitis when added to the FDA approved treatment dupilumab for atopic dermatitis that is not providing adequate clinical responses.

Study Overview

• Status: Completed
• Conditions: Atopic Dermatitis
• Intervention / Treatment: Drug: Apremilast

Detailed Description

The purpose of this study is to determine if apremilast as a combined treatment for atopic dermatitis will provide increased efficacy outcomes in subjects who are currently using the FDA approved therapy of dupilumab but have responded only partially or inadequately to this therapy. Our hypothesis is that adding apremilast will allow patients to go from an inadequate response to dupilumab to an adequate response defined as an Investigator Global Assessment (IGA) of 0 (clear) or 1 (almost clear).

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center, Department of Dermatology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Signed and dated informed consent indicating the subject has been informed of all aspects of the study
2. Subject is willing and able to comply with treatment plan, study drug administration, and study protocol requirements
3. Subject has a documented clinical diagnosis of chronic atopic dermatitis for at least 6 months prior to screening visit and is a candidate for systemic therapy

4. Subjects must fulfill criteria outlined in the following clinical categories:

   • Subjects must be currently using and experiencing an inadequate response to dupilumab which is FDA approved for the treatment of moderate to severe atopic dermatitis. An inadequate response is defined as an IGA of 2 or more.
   • At the time of screening, subject must have a partial or inadequate response to their current treatment regimen. A partial or inadequate response at screening is defined as having both of the following:
   • Not having achieved an Investigator's Global Assessment score of 0 (clear) or 1 (almost clear).
   • Subjects must be on dupilumab for at least 12 weeks and willing to continue on dupilumab on a stable dose (40 mg weekly or every other week) while also receiving the study drug
5. 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
6. 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 non-latex condom NOT made out of natural [animal] membrane [for example, polyurethane]) while on study medication and for at least 28 days after the last dose of study medication
7. If receiving concomitant medications for any reason, must be on a stable regimen and willing to stay on a stable regimen. This includes emollients, which should stay stable throughout the study

Exclusion Criteria:

1. Prior hypersensitivity reaction or exposure to apremilast 2. Untreated or unstable depression or suicidality, including prior history of suicide attempt at any time in the subject's lifetime prior to Baseline Visit or major psychiatric illness requiring hospitalization within 3 years prior to Baseline Visit. Depression and suicidality will be assessed through standard-of-care questioning 3. Other than atopic dermatitis, any clinically significant (as determined by the Investigator) cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, immunologic disease, or other major disease that is currently uncontrolled 4. Any condition, 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 6. Pregnant or lactating females 7. Concomitant therapy with CYP450 enzyme inducers (e.g., rifampin, phenobarbital, carbamazepine, phenytoin), which may cause loss of efficacy of apremilast.

8. Prolonged sun exposure or use of tanning booths, which may confound the ability to interpret data from the study.

9. Active substance abuse or a history of substance abuse within 6 months prior to Screening. Subjects will be asked about any history of substance use using standard of care questioning.

10. Malignancy or history of malignancy, except for:

• treated [i.e., cured] basal cell or squamous cell in situ skin carcinomas;

• treated [i.e., cured] cervical intraepithelial neoplasia (CIN) or carcinoma in situ of cervix with no evidence of recurrence within the previous 5 years.

  11. Use of dupilumab in combination with any other systemic immunosuppressant medication within 4 weeks prior to randomization or 5 pharmacokinetic/pharmacodynamic half lives, whichever is longer.

  12. Use of any investigational drug within 4 weeks prior to randomization, or 5 pharmacokinetic/pharmacodynamic half lives, if known (whichever is longer)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Apremilast; Apremilast will be administered to patients as 30 mg oral tablets taken twice daily for 24 weeks. An initial 5-day titration will be implemented to improve tolerability.	Drug: Apremilast; 30 mg twice daily (BID); Other Names: Otezla

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Patients Who Achieve an Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 16.	Clinical improvement in a patient's eczematous lesions corresponds with a decrease in IGA, and a score of 0 (clear) or 1 (almost clear) is considered a significant clinical response.	week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects Achieving Body Surface Area Less Than 3% at Week 16		Week 16
Body Surface Area (BSA) Involvement		Baseline to Week 16
Dermatology Life Quality Index (DLQI) Score	10-item questionnaire that measures how much the subjects' skin disease has affected their quality of life over the past week. Total score range 0 to 30, a score equal to zero (0) represents no impact and a score equal to thirty (30) represents severe impact on quality of life.	baseline to Week 16
Numerical Rating Scale (NRS) Pruritus Scale	zero (0) to ten (10) numerical rating scale, zero equals no itch and ten equals worst itch imaginable.	Baseline - Week 16
Eczema Area and Severity Index (EASI) Score	score ranges from zero (0) to seventy- two (72), 0 indicates no active eczema / atopic dermatitis, max score 72 indicates severe eczema involvement of all body regions.	Baseline to Week 16

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Analysis	Safety and tolerability will be evaluated by tabulations of adverse events	24 weeks

Collaborators and Investigators

• Sponsor: Tufts Medical Center
• Collaborators: Amgen
• Investigators: Principal Investigator: David Rosmarin, MD, Tufts Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2020
• Primary Completion (Actual): June 23, 2022
• Study Completion (Actual): August 18, 2022

Study Registration Dates

• First Submitted: March 4, 2020
• First Submitted That Met QC Criteria: March 10, 2020
• First Posted (Actual): March 13, 2020

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Eczema; Dermatitis, Atopic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 4 Inhibitors; Apremilast
• Other Study ID Numbers: 13305

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes