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Pilot Study of the Safety and Efficacy of Apremilast in Subjects With Moderate to Severe Alopecia Areata

Primary Purpose

Alopecia Areata

Status
Unknown status
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Apremilast
Placebo
Sponsored by
Icahn School of Medicine at Mount Sinai
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alopecia Areata focused on measuring Alopecia areata

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Males or females, 18 years or older at the time of signing the informed consent document.

Understand and voluntarily sign an informed consent document prior to any study-related assessments/procedures are conducted.

Able to adhere to the study visit schedule and other protocol requirements. Subject with a diagnosis of patchy scalp alopecia areata present for at least 6 months, and up to a maximum of 10 years.

Patients with ≥50% and <95% total scalp hair loss at Baseline as measured using the SALT score to qualify as moderate to severe AA; and 95%-100% scalp hair loss to qualify as AA totalis/universalis.

Must meet the following laboratory criteria White blood cell count ≥ 3000/mm3 (≥ 3.0 x 109/L) and < 14,000/mm3 (< 14 x 109/L). Platelet count ≥ 100,000/μL (≥ 100 x 109/L). Serum creatinine ≤ 1.5 mg/dL (≤ 132.6 μmol/L). AST (SGOT) and ALT (SGPT) ≤ 2 x upper limit of normal (ULN). If the initial test shows ALT or AST > 2 times the ULN, one repeat test is allowed during the Screening Phase.

Total bilirubin ≤ 2 mg/dL (34 μmol/L). If the initial test shows total bilirubin > 2 mg/dL (34 μmol/L), one repeat test is allowed during the Screening Phase.

Hemoglobin ≥ 10 g/dL (≥ 6.2 mmol/L).

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 (IP), 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 spermicide PLUS one additional barrier method: (a) diaphragm with spermicide; (b) cervical cap with spermicide; or (c) contraceptive sponge with spermicide.

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 nonlatex condom NOT made out of natural [animal] membrane [for example, polyurethane]) while on IP and for at least 28 days after the last dose of IP.

No evidence of hair regrowth present at Baseline.

EXCLUSION CRITERIA:

The presence of any of the following will exclude a subject from enrollment:

Clinically significant (as determined by the investigator) cardiac, endocrine, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, or immunologic disease, or other major uncontrolled diseases that will affect the health of the subject during the study or interfere with the interpretation of study results.

Hepatitis B surface antigen positive at Screening (Visit 1). Hepatitis C antibody positive at Screening (Visit 1). History of positive human immunodeficiency virus (HIV), or congenital or acquired immunodeficiency (eg, Common Variable Immunodeficiency [CVID]). Subjects deemed at risk by the study investigator, may also undergo testing for human immunodeficiency virus (HIV). Subjects deemed at risk include those with a history of injection drug use, homosexual subjects, and subjects with known sexual contact with an HIV positive partner.

Active TB or a history of inadequately treated TB. Active substance abuse or a history of substance abuse within six months prior to Screening.

Pregnant or breast feeding. History of allergy to any component of the IP.

Major surgery within eight weeks prior to Screening (Visit 1) and/or planned surgery during the length of the study.

Malignancy or history of malignancy, except for:

treated (ie, cured) basal cell or squamous cell in situ skin carcinomas; treated (ie, cured) cervical intraepithelial neoplasia (CIN) or carcinoma in situ of the cervix with no evidence of recurrence within 5 years prior to Screening (Visit 1).

Unstable asthma (eg, acute episodes of exacerbation [nocturnal episodes, sudden episodes triggered by unidentifiable factors] despite a stable regimen of anti-asthmatic medications); prior episode(s) of life-threatening asthma; or asthma that requires inhaled budesonide or equivalent at >1200 μg/day or fluticasone propionate at > 880 μg/day along with another anti-asthmatic drug such as a long-acting beta-agonist.

A history of and/or concurrent condition of serious hypersensitivity (eg, anaphylaxis) to drugs, foods, or other allergens without access to emergency rescue medication such as epinephrine.

Persistent or recurring bacterial infection requiring systemic antibiotics, or clinically significant viral or fungal infections, within two weeks of Screening (Visit 1). Any treatment for such infections must have been completed at least two weeks prior to the Screening Visit and no new/recurrent infections should have occurred prior to the Baseline Visit.

Active skin infection requiring systemic antimicrobials at Baseline/Randomization (Visit 2).

Skin lesion(s) due to conditions other than AA that would interfere with the study specified assessments.

Prior treatment with apremilast, or participation in a clinical study involving apremilast.

Use of phototherapy (ie, UVB, UVA) or systemic immunosuppressive drugs (including, but not limited to, cyclosporine, corticosteroids, mycophenolate mofetil, azathioprine, Methotrexate, or tacrolimus), or oral preparations of herbal immunomodulatory medications within four weeks prior to Baseline/Randomization (Visit 2).

Use of interferon-γ within 12 weeks prior to Baseline/Randomization (Visit 2). Use of abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, or tocilizumab within 12 weeks prior to Baseline/Randomization (Visit 2).

Use of oral janus kinase (JAK) inhibitors (e.g. tofacitinib, ruxolitinib) within 12 weeks prior to Baseline/Randomization (Visit 2).

Use of omalizumab, rituximab, ustekinumab, alefacept, briakinumab, or other therapeutic antibody products within 24 weeks prior to Baseline/Randomization (Visit 2).

Use of any investigational drug within four weeks or five PK or PD half lives (whichever is longer) prior to Baseline/Randomization (Visit 2).

Use of topical corticosteroid preparations, topical calcineurin inhibitors, or other topical preparations with immunomodulatory properties within 2 weeks prior to Baseline/Randomization (Visit 2).

Prior history of suicide attempt at any time in the subject's lifetime prior to Baseline (Visit 2) or major psychiatric illness requiring hospitalization within 3 years prior to Baseline (Visit 2).

History of male or female pattern hair loss Ludwig stage III or Hamilton > stage V.

Patients in whom the diagnosis of alopecia areata is in question, or subjects with scarring alopecia.

Sites / Locations

  • Icahn School of Medicine at Mount Sinai

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Apremilast

Placebo

Arm Description

Apremilast 30mg twice daily

Placebo pills twice daily

Outcomes

Primary Outcome Measures

SALT50
Percentage of patients achieving 50% or greater improvement in their Severity of Alopecia Tool (SALT) score (SALT50) at Week 24 compared to Baseline.

Secondary Outcome Measures

aaPGA
2) Proportion of subjects achieving an alopecia areata Physician's Global Assessment (aaPGA) score of 3 or above at Weeks 24 (0, no regrowth; 1, <25% of regrowth; 2, 25%-49% of regrowth; 3, 50%-74% of regrowth; 4, 75%-99% of re- growth; 5, 100% of regrowth).
aaPGA
2) Proportion of subjects achieving an alopecia areata Physician's Global Assessment (aaPGA) score of 3 or above at Weeks 48 (0, no regrowth; 1, <25% of regrowth; 2, 25%-49% of regrowth; 3, 50%-74% of regrowth; 4, 75%-99% of re- growth; 5, 100% of regrowth).
AASIS
Percentage change from Baseline in the Alopecia Areata Symptom Impact Scale (AASIS) at Weeks 24.
AASIS
Percentage change from Baseline in the Alopecia Areata Symptom Impact Scale (AASIS) at Weeks 48.
AA-QoL
Percentage change from baseline in the Alopecia Areata Quality of Life questionnaire (AA-QoL) at Weeks 24.
AA-QoL
Percentage change from baseline in the Alopecia Areata Quality of Life questionnaire (AA-QoL) at Weeks 48.
Semiquantitative score
Semiquantitative score using SALT subclasses (0, no hair loss; 1, <25% hair loss; 2, 25%-49% hair loss; 3, 50%-74% hair loss; 4, 75%-99% hair loss; 5, 100% hair loss) at week 24.
Semiquantitative score
Semiquantitative score using SALT subclasses (0, no hair loss; 1, <25% hair loss; 2, 25%-49% hair loss; 3, 50%-74% hair loss; 4, 75%-99% hair loss; 5, 100% hair loss) at week 48.

Full Information

First Posted
February 11, 2016
Last Updated
January 16, 2018
Sponsor
Icahn School of Medicine at Mount Sinai
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1. Study Identification

Unique Protocol Identification Number
NCT02684123
Brief Title
Pilot Study of the Safety and Efficacy of Apremilast in Subjects With Moderate to Severe Alopecia Areata
Official Title
A Randomized Placebo-controlled Single Center Pilot Study of the Safety and Efficacy of Apremilast in Subjects With Moderate to Severe Alopecia Areata
Study Type
Interventional

2. Study Status

Record Verification Date
January 2018
Overall Recruitment Status
Unknown status
Study Start Date
February 2016 (undefined)
Primary Completion Date
December 2018 (Anticipated)
Study Completion Date
December 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Icahn School of Medicine at Mount Sinai

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Alopecia areata is a medical condition, in which the hair falls out in patches. The hair can fall out on the scalp or elsewhere on the face and body. Alopecia areata is an autoimmune skin disease, which means that the immune system is recognizing the hair follicles as foreign and attacking them, causing round patches of hair loss. It can progress to total scalp hair loss (alopecia totalis) or complete body hair loss (alopecia universalis). The scalp is the most commonly affected area, but the beard or any hair-bearing site can be affected alone or together with the scalp. Alopecia areata occurs in males and females of all ages, and is a highly unpredictable condition that tends to recur. Alopecia areata can cause significant distress to both patients and their families. In this study, the aim to assess the effects of a new treatment called apremilast in patients with alopecia areata. A total of 30 patients will be included in the study, which will run for a total of 52 weeks.
Detailed Description
This is a randomized, double-blind, placebo-controlled pilot study consisting of two phases. A total of 30 subjects with moderate to severe alopecia areata (including universalis and totalis) involving 50-100% of the scalp will be enrolled. A possible maximum of 15 patients (approximately 7 patients each) with current episodes of AA totalis / universalis may be included in this study. In Phase 1, subjects will be randomized (2:1) to either receive apremilast or placebo for 24 weeks. In Phase 2, eligible subjects will receive apremilast from Week 24 through Week 48. The following subjects will be eligible to enter into Phase 2: Subjects who received placebo in Phase 1 of the study Subjects who received apremilast in Phase 1 of the study, and who achieved a minimum of 50% regrowth (SALT50) at Week 24, compared to Baseline.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alopecia Areata
Keywords
Alopecia areata

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Apremilast
Arm Type
Active Comparator
Arm Description
Apremilast 30mg twice daily
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo pills twice daily
Intervention Type
Drug
Intervention Name(s)
Apremilast
Other Intervention Name(s)
Otezla
Intervention Description
Subjects will get drug or placebo
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
SALT50
Description
Percentage of patients achieving 50% or greater improvement in their Severity of Alopecia Tool (SALT) score (SALT50) at Week 24 compared to Baseline.
Time Frame
Baseline and Week 24
Secondary Outcome Measure Information:
Title
aaPGA
Description
2) Proportion of subjects achieving an alopecia areata Physician's Global Assessment (aaPGA) score of 3 or above at Weeks 24 (0, no regrowth; 1, <25% of regrowth; 2, 25%-49% of regrowth; 3, 50%-74% of regrowth; 4, 75%-99% of re- growth; 5, 100% of regrowth).
Time Frame
Week 24
Title
aaPGA
Description
2) Proportion of subjects achieving an alopecia areata Physician's Global Assessment (aaPGA) score of 3 or above at Weeks 48 (0, no regrowth; 1, <25% of regrowth; 2, 25%-49% of regrowth; 3, 50%-74% of regrowth; 4, 75%-99% of re- growth; 5, 100% of regrowth).
Time Frame
Week 48
Title
AASIS
Description
Percentage change from Baseline in the Alopecia Areata Symptom Impact Scale (AASIS) at Weeks 24.
Time Frame
Baseline and Weeks 24
Title
AASIS
Description
Percentage change from Baseline in the Alopecia Areata Symptom Impact Scale (AASIS) at Weeks 48.
Time Frame
Baseline and Weeks 48
Title
AA-QoL
Description
Percentage change from baseline in the Alopecia Areata Quality of Life questionnaire (AA-QoL) at Weeks 24.
Time Frame
Baseline and Weeks 24
Title
AA-QoL
Description
Percentage change from baseline in the Alopecia Areata Quality of Life questionnaire (AA-QoL) at Weeks 48.
Time Frame
Baseline and Weeks 48
Title
Semiquantitative score
Description
Semiquantitative score using SALT subclasses (0, no hair loss; 1, <25% hair loss; 2, 25%-49% hair loss; 3, 50%-74% hair loss; 4, 75%-99% hair loss; 5, 100% hair loss) at week 24.
Time Frame
Baseline and Weeks 24
Title
Semiquantitative score
Description
Semiquantitative score using SALT subclasses (0, no hair loss; 1, <25% hair loss; 2, 25%-49% hair loss; 3, 50%-74% hair loss; 4, 75%-99% hair loss; 5, 100% hair loss) at week 48.
Time Frame
Baseline and Weeks 48

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Males or females, 18 years or older at the time of signing the informed consent document. Understand and voluntarily sign an informed consent document prior to any study-related assessments/procedures are conducted. Able to adhere to the study visit schedule and other protocol requirements. Subject with a diagnosis of patchy scalp alopecia areata present for at least 6 months, and up to a maximum of 10 years. Patients with ≥50% and <95% total scalp hair loss at Baseline as measured using the SALT score to qualify as moderate to severe AA; and 95%-100% scalp hair loss to qualify as AA totalis/universalis. Must meet the following laboratory criteria White blood cell count ≥ 3000/mm3 (≥ 3.0 x 109/L) and < 14,000/mm3 (< 14 x 109/L). Platelet count ≥ 100,000/μL (≥ 100 x 109/L). Serum creatinine ≤ 1.5 mg/dL (≤ 132.6 μmol/L). AST (SGOT) and ALT (SGPT) ≤ 2 x upper limit of normal (ULN). If the initial test shows ALT or AST > 2 times the ULN, one repeat test is allowed during the Screening Phase. Total bilirubin ≤ 2 mg/dL (34 μmol/L). If the initial test shows total bilirubin > 2 mg/dL (34 μmol/L), one repeat test is allowed during the Screening Phase. Hemoglobin ≥ 10 g/dL (≥ 6.2 mmol/L). 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 (IP), 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 spermicide PLUS one additional barrier method: (a) diaphragm with spermicide; (b) cervical cap with spermicide; or (c) contraceptive sponge with spermicide. 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 nonlatex condom NOT made out of natural [animal] membrane [for example, polyurethane]) while on IP and for at least 28 days after the last dose of IP. No evidence of hair regrowth present at Baseline. EXCLUSION CRITERIA: The presence of any of the following will exclude a subject from enrollment: Clinically significant (as determined by the investigator) cardiac, endocrine, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, or immunologic disease, or other major uncontrolled diseases that will affect the health of the subject during the study or interfere with the interpretation of study results. Hepatitis B surface antigen positive at Screening (Visit 1). Hepatitis C antibody positive at Screening (Visit 1). History of positive human immunodeficiency virus (HIV), or congenital or acquired immunodeficiency (eg, Common Variable Immunodeficiency [CVID]). Subjects deemed at risk by the study investigator, may also undergo testing for human immunodeficiency virus (HIV). Subjects deemed at risk include those with a history of injection drug use, homosexual subjects, and subjects with known sexual contact with an HIV positive partner. Active TB or a history of inadequately treated TB. Active substance abuse or a history of substance abuse within six months prior to Screening. Pregnant or breast feeding. History of allergy to any component of the IP. Major surgery within eight weeks prior to Screening (Visit 1) and/or planned surgery during the length of the study. Malignancy or history of malignancy, except for: treated (ie, cured) basal cell or squamous cell in situ skin carcinomas; treated (ie, cured) cervical intraepithelial neoplasia (CIN) or carcinoma in situ of the cervix with no evidence of recurrence within 5 years prior to Screening (Visit 1). Unstable asthma (eg, acute episodes of exacerbation [nocturnal episodes, sudden episodes triggered by unidentifiable factors] despite a stable regimen of anti-asthmatic medications); prior episode(s) of life-threatening asthma; or asthma that requires inhaled budesonide or equivalent at >1200 μg/day or fluticasone propionate at > 880 μg/day along with another anti-asthmatic drug such as a long-acting beta-agonist. A history of and/or concurrent condition of serious hypersensitivity (eg, anaphylaxis) to drugs, foods, or other allergens without access to emergency rescue medication such as epinephrine. Persistent or recurring bacterial infection requiring systemic antibiotics, or clinically significant viral or fungal infections, within two weeks of Screening (Visit 1). Any treatment for such infections must have been completed at least two weeks prior to the Screening Visit and no new/recurrent infections should have occurred prior to the Baseline Visit. Active skin infection requiring systemic antimicrobials at Baseline/Randomization (Visit 2). Skin lesion(s) due to conditions other than AA that would interfere with the study specified assessments. Prior treatment with apremilast, or participation in a clinical study involving apremilast. Use of phototherapy (ie, UVB, UVA) or systemic immunosuppressive drugs (including, but not limited to, cyclosporine, corticosteroids, mycophenolate mofetil, azathioprine, Methotrexate, or tacrolimus), or oral preparations of herbal immunomodulatory medications within four weeks prior to Baseline/Randomization (Visit 2). Use of interferon-γ within 12 weeks prior to Baseline/Randomization (Visit 2). Use of abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, or tocilizumab within 12 weeks prior to Baseline/Randomization (Visit 2). Use of oral janus kinase (JAK) inhibitors (e.g. tofacitinib, ruxolitinib) within 12 weeks prior to Baseline/Randomization (Visit 2). Use of omalizumab, rituximab, ustekinumab, alefacept, briakinumab, or other therapeutic antibody products within 24 weeks prior to Baseline/Randomization (Visit 2). Use of any investigational drug within four weeks or five PK or PD half lives (whichever is longer) prior to Baseline/Randomization (Visit 2). Use of topical corticosteroid preparations, topical calcineurin inhibitors, or other topical preparations with immunomodulatory properties within 2 weeks prior to Baseline/Randomization (Visit 2). Prior history of suicide attempt at any time in the subject's lifetime prior to Baseline (Visit 2) or major psychiatric illness requiring hospitalization within 3 years prior to Baseline (Visit 2). History of male or female pattern hair loss Ludwig stage III or Hamilton > stage V. Patients in whom the diagnosis of alopecia areata is in question, or subjects with scarring alopecia.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Emma Guttman, MD, PhD
Organizational Affiliation
ISMMS
Official's Role
Principal Investigator
Facility Information:
Facility Name
Icahn School of Medicine at Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
18209089
Citation
Haider AS, Lowes MA, Suarez-Farinas M, Zaba LC, Cardinale I, Khatcherian A, Novitskaya I, Wittkowski KM, Krueger JG. Identification of cellular pathways of "type 1," Th17 T cells, and TNF- and inducible nitric oxide synthase-producing dendritic cells in autoimmune inflammation through pharmacogenomic study of cyclosporine A in psoriasis. J Immunol. 2008 Feb 1;180(3):1913-20. doi: 10.4049/jimmunol.180.3.1913.
Results Reference
background
PubMed Identifier
23159179
Citation
Alkhalifah A. Alopecia areata update. Dermatol Clin. 2013 Jan;31(1):93-108. doi: 10.1016/j.det.2012.08.010. Epub 2012 Oct 2.
Results Reference
background
PubMed Identifier
22949325
Citation
Croxford AL, Mair F, Becher B. IL-23: one cytokine in control of autoimmunity. Eur J Immunol. 2012 Sep;42(9):2263-73. doi: 10.1002/eji.201242598.
Results Reference
background
PubMed Identifier
25427848
Citation
Vaccaro M, Cannavo SP, Imbesi S, Cristani M, Barbuzza O, Tigano V, Gangemi S. Increased serum levels of interleukin-23 circulating in patients with non-segmental generalized vitiligo. Int J Dermatol. 2015 Jun;54(6):672-4. doi: 10.1111/ijd.12392. Epub 2014 Nov 27.
Results Reference
background

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Pilot Study of the Safety and Efficacy of Apremilast in Subjects With Moderate to Severe Alopecia Areata

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