A Study of SM04554 Applied Topically to the Scalp of Male Subjects With Androgenetic Alopecia Analyzed by Biopsy of the Scalp Prior To and Post Dosing

Study Overview
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Brief Summary
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This study will assess the safety, tolerability, and efficacy of SM04554 at concentrations of 0.15% and 0.25%. Improved knowledge of the changes in hair counts and immunohistochemical analysis associated with androgenetic alopecia (AGA) before and after treatment with SM04554 and compared to placebo may lead to a greater understanding of the underlying mechanisms of action of SM04554.

Official Title
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A Phase 2, Multicenter, Randomized, Double-Blind Study of SM04554 Applied Topically to the Scalp of Male Subjects With Androgenetic Alopecia (AGA) Analyzed by Biopsy of the Scalp Prior To and Post Dosing

Conditions
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Androgenetic Alopecia

Intervention / Treatment
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* Drug: Topical SM04554 solution
* Drug: Topical Vehicle solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of AGA with Norwood-Hamilton Classification score of 4, 5, 5A, 5V, or 6 In good general health, as determined by the Investigator Willing and able to attend all study visits Willing to undergo two punch biopsies of the scalp Willing to inform females, with whom they may interact, that they are using a topical investigational product and direct contact should be avoided as potential harm to a fetus is unknown Willing to not use permanent or semi-permanent hair products (e.g., color, texturizers, relaxers) for the duration of the study; daily styling products will be allowed on non-study visit days (e.g., hair gel, mousse, styling spray) Willing to use sponsor-supplied shampoo and conditioner in place of regular shampoo and conditioner, for the duration of the study; use of sponsor-supplied conditioner is optional for subjects who do not use conditioner Exclusion Criteria: Clinical diagnosis of alopecia areata or other non-AGA forms of alopecia Scalp hair loss on the treatment area, due to disease, injury, or medical therapy Males who are sexually active and have a partner who is capable of becoming pregnant, neither of whom have had surgery to become sterilized, that are not using a highly effective method of birth control and are not willing to use a highly effective method of birth control during the study treatment period until 90 days post last dose of study medication Current skin disease (e.g., psoriasis, atopic dermatitis, eczema, sun damage, seborrheic dermatitis, actinic keratosis), cuts and/or abrasions on the scalp or hands or condition (e.g., sunburn, tattoos) on the treatment area or hands that, in the opinion of the Investigator, might put the subject at risk or interfere with the study conduct or evaluations History of or current skin cancer (e.g., melanoma, basal cell carcinoma, squamous cell carcinoma) located anywhere on the body History of surgical correction of hair loss on the scalp Previous exposure to SM04554 Use of blood thinners (e.g., Coumadin, Plavix, Lovenox, and aspirin >81mg); low dose aspirin (e.g., ≤81 mg) is allowable Use of any products or devices clinically proven to promote scalp hair growth (e.g., finasteride or minoxidil) within 24 weeks prior to study start Use of anti-androgenic therapies (e.g., spironolactone, flutamide, cyproterone acetate, cimetidine) within 12 weeks prior to study start Use of semi-permanent hair products (e.g., color, texturizers, relaxers) within 30 days prior to study start Use of medicated shampoo or conditioner (medicated shampoo and conditioner refer to any prescription shampoo or conditioner as well as any over-the-counter medicated shampoo or conditioner, such as those for treatment of dandruff or promoting hair growth) within 30 days prior to study start History of hair transplants Current use of an occlusive wig, hair extensions, or hair weaves Participation in any other investigational drug or medical device trial which included administration of an investigational study medication or medical device, within 30 days or 5 half-lives of the investigational agent, whichever is longer, prior to study start Poor peripheral venous access Subjects unwilling to refrain from sperm donation during the study treatment period until 90 days post last dose of study medication Subjects with pregnant partners at study start Subjects who are immediate family members (spouse, parent, child, or sibling; biological or legally adopted) of personnel directly affiliated with the study at the investigative site, or are directly affiliated with the study at the investigative site Subjects employed by Samumed, LLC, or any of its affiliates or development partners (that is, an employee, temporary contract worker, or designee) responsible for the conduct of the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Arm 1<br>Topical SM04554 0.15% solution, once daily for approximately 90 days | Drug: Topical SM04554 solution<br> <br> |
| Experimental: Experimental Arm 2<br>Topical SM04554 0.25% solution, once daily for approximately 90 days | Drug: Topical SM04554 solution<br> <br> |
| Placebo Comparator: Vehicle<br>Topical vehicle solution, once daily for approximately 90 days | Drug: Topical Vehicle solution<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in number of terminal hair follicles | Scalp biopsies obtained prior to initiating therapy and after 90 days of therapy will be compared to determine the change in number of terminal hair follicles over the treatment period. | Baseline and Day 91 | 
| Change in number of anagen hair follicles | Scalp biopsies obtained prior to initiating therapy and after 90 days of therapy will be compared to determine the change in number of anagen hair follicles over the treatment period. | Baseline and Day 91 | 
| Change in number of telogen hair follicles | Scalp biopsies obtained prior to initiating therapy and after 90 days of therapy will be compared to determine the change in number of telogen hair follicles over the treatment period. | Baseline and Day 91 | 
| Change in number of catagen hair follicles | Scalp biopsies obtained prior to initiating therapy and after 90 days of therapy will be compared to determine the change in number of catagen hair follicles over the treatment period. | Baseline and Day 91 | 
| Change in number of vellus (vellus-like) miniaturized hair follicles | Scalp biopsies obtained prior to initiating therapy and after 90 days of therapy will be compared to determine the change in number of vellus (vellus-like) miniaturized hair follicles over the treatment period. | Baseline and Day 91 | 
| Change in number of indeterminate hair follicles | Scalp biopsies obtained prior to initiating therapy and after 90 days of therapy will be compared to determine the change in number of indeterminate hair follicles over the treatment period. | Baseline and Day 91 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in number of terminal hair follicles | Scalp biopsies obtained prior to initiating therapy, after 90 days of therapy, and after an additional 45 days off therapy will be compared to determine the change in the number of terminal hair follicles over the treatment and off-treatment periods. | Baseline, Day 91 and Day 135 | 
| Change in number of anagen hair follicles | Scalp biopsies obtained prior to initiating therapy, after 90 days of therapy, and after an additional 45 days off therapy will be compared to determine the change in the number of anagen hair follicles over the treatment and off-treatment periods. | Baseline, Day 91 and Day 135 | 
| Change in number of telogen hair follicles | Scalp biopsies obtained prior to initiating therapy, after 90 days of therapy, and after an additional 45 days off therapy will be compared to determine the change in the number of telogen hair follicles over the treatment and off-treatment periods. | Baseline, Day 91 and Day 135 | 
| Change in number of catagen hair follicles | Scalp biopsies obtained prior to initiating therapy, after 90 days of therapy, and after an additional 45 days off therapy will be compared to determine the change in the number of catagen hair follicles over the treatment and off-treatment periods. | Baseline, Day 91 and Day 135 | 
| Change in number of vellus (vellus-like) miniaturized hair follicles | Scalp biopsies obtained prior to initiating therapy, after 90 days of therapy, and after an additional 45 days off therapy will be compared to determine the change in the number of vellus (vellus-like) miniaturized hair follicles over the treatment and off-treatment periods. | Baseline, Day 91 and Day 135 | 
| Change in number of indeterminate hair follicles | Scalp biopsies obtained prior to initiating therapy, after 90 days of therapy, and after an additional 45 days off therapy will be compared to determine the change in the number of indeterminate hair follicles over the treatment and off-treatment periods. | Baseline, Day 91 and Day 135 | 
| Change in density of hair follicles | Scalp biopsies obtained prior to initiating therapy, after 90 days of therapy, and after an additional 45 days off therapy will be compared to determine the change in density of hair follicles over the treatment and off-treatment periods. | Baseline, Day 91 and Day 135 | 
| Ratio of terminal to miniaturized hair follicles (indeterminate hair and vellus hair follicles) | Scalp biopsies obtained prior to initiating therapy, after 90 days of therapy, and after an additional 45 days off therapy will be used to determine the ratio of terminal to miniaturized hair follicles during the treatment and off-treatment periods. | Baseline, Day 91 and Day 135 | 
| Change in nuclear expression of beta-catenin | Scalp biopsies obtained prior to initiating therapy, after 90 days of therapy, and after an additional 45 days off therapy will be compared to determine the change in nuclear expression of beta-catenin over the treatment and off-treatment periods. | Baseline, Day 91 and Day 135 | 
| Change in Ki-67 index in epidermis and hair follicles | Scalp biopsies obtained prior to initiating therapy, after 90 days of therapy, and after an additional 45 days off therapy will be compared to determine the change in Ki-67 index in epidermis and hair follicles over the treatment and off-treatment periods. | Baseline, Day 91 and Day 135 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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male pattern baldness, SM04554, AGA