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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04306965

Enrollment

Registered

2020-03-13

Start date

2020-08-01

Completion date

2022-08-18

Last updated

2024-04-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Atopic Dermatitis

Brief summary

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.

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).

Interventions

DRUGApremilast

30 mg twice daily (BID)

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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)

Design outcomes

Primary

Measure	Time frame	Description
Proportion of Patients Who Achieve an Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 16.	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.

Secondary

Measure	Time frame	Description
Percentage of Subjects Achieving Body Surface Area Less Than 3% at Week 16	Week 16	—
Body Surface Area (BSA) Involvement	Baseline to Week 16	—
Numerical Rating Scale (NRS) Pruritus Scale	Baseline - Week 16	zero (0) to ten (10) numerical rating scale, zero equals no itch and ten equals worst itch imaginable.
Eczema Area and Severity Index (EASI) Score	Baseline to Week 16	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.
Dermatology Life Quality Index (DLQI) Score	baseline to Week 16	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.

Other

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

Countries

United States

Participant flow

Participants by arm

Arm	Count
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. Apremilast: 30 mg BID	10
Total	10

Baseline characteristics

Characteristic	Apremilast
Age, Continuous	42 years STANDARD_DEVIATION 21.7
baseline Body Surface Area (BSA), %	9.99 % percentage of body surface area STANDARD_DEVIATION 6.3
Baseline Dermatology Life Quality Index (DLQI)	7.6 score on a scale STANDARD_DEVIATION 5.4
Baseline Eczema Area and Severity Index (EASI)	7.4 score on a scale STANDARD_DEVIATION 3.2
Baseline Numerical Rating Scale (NRS) pruritus	5.0 score on a scale STANDARD_DEVIATION 2.4
concomitant topical steroid use	4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Investigator Global Assessment Score IGA score 2 (Mild)	3 Participants
Investigator Global Assessment Score IGA score 3 (Moderate)	7 Participants
mean duration of atopic dermatitis	18.6 years STANDARD_DEVIATION 10.2
% patients with allergic rhinitis	8 Participants
% patients with asthma	8 Participants
% patients with food allergy	6 Participants
prior atopic dermatitis treatments , % immunosuppressants	7 Participants
prior atopic dermatitis treatments , % phototherapy	1 Participants
prior atopic dermatitis treatments , % prednisone	6 Participants
prior atopic dermatitis treatments , % topical calcineurin inhibitor	7 Participants
prior atopic dermatitis treatments , % topical corticosteroids	10 Participants
prior atopic dermatitis treatments , % topical phosphodiesterase-4 inhibitor	5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	4 Participants
Race (NIH/OMB) Black or African American	1 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	5 Participants
Sex: Female, Male Female	2 Participants
Sex: Female, Male Male	8 Participants
time on dupilumab therapy	20.3 months STANDARD_DEVIATION 14.3
weight in kg	86.38 kilograms STANDARD_DEVIATION 19

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 10
other Total, other adverse events	8 / 10
serious Total, serious adverse events	0 / 10

Outcome results

Primary

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.

Time frame: week 16