Safety and efficacy of ALRV5XR in men with androgenetic alopecia: A randomised, double-blinded, placebo-controlled clinical trial

Peter R Feldman, Klaus M Fiebig, Charles Piwko, Boris M Mints, Dennis Brown, Deborah J Cahan, Jaime Guevara-Aguirre, Peter R Feldman, Klaus M Fiebig, Charles Piwko, Boris M Mints, Dennis Brown, Deborah J Cahan, Jaime Guevara-Aguirre

Abstract

Background: Androgenetic alopecia (AGA) is the most common hair loss disorder seen in men. It can have an early onset but has also been associated with ageing and senescence. It often induces pronounced psychological impact. ALRV5XR, a new hair loss treatment herein evaluated, was designed to target multiple molecular pathways involved in hair growth and hair follicle stem cell biology. The main objectives of the study were the assessment of safety and efficacy profiles of ALRV5XR in men.

Methods: This 24-week, parallel randomised, placebo-controlled, double-blinded clinical trial was performed in a USA community clinic. Healthy men (age 22-65) with AGA and belonging to the Hamilton-Norwood (HN) classification I-VII and Fitzpatrick skin type (FST) I-VI, were randomly allocated in a 1:1 ratio into ALRV5XR or placebo treatment groups. Dermatologist assessment, phototrichograms, and blood samples were obtained in a blinded fashion at baseline, 12 and 24 weeks. Subjects were given a masked treatment consisting of oral capsules, shampoo, conditioner, and follicle serum, which was intended for daily use. Efficacy was assessed via absolute and per cent changes in terminal hair (TH) density, and response rates. The trial was registered with clinicaltrials.gov (NCT04450589) and is completed.

Findings: Forty-six subjects were enroled in the study, 23 allocated to the ALRV5XR treatment and 23 to the placebo group. Enrolment occurred from April 11 to October 23, 2018. Thirty-six subjects completed the trial (17 ALRV5XR, 19 placebo) and 11 subjects in each group were evaluable for TH outcomes. At 24 weeks, the absolute change in TH density improved by 21·0 THs/cm2 (95% CI: 9·2-32·8; p = 0·0014), and the relative density increased by 16·4% (95% CI: 7·4%-25·5%; p = 0·0012). The odds ratio for being a responder (≥ 0 change) was 87·4. TH density increased linearly and was not affected by HN, FST, ethnicity, age, or body mass index. All subjects in the ALRV5XR group responded to treatment while 81·8% of the placebo group decreased TH density. ALRV5XR induced statistically significant changes in both decrease in vellus hair (VH) density as well as in concomitant increase of the TH/VH ratio when compared to placebo. ALRV5XR was well tolerated, and no adverse events were observed.

Interpretation: ALRV5XR treatment resulted in clinically significant TH regrowth in men with AGA. Furthermore, it appeared to reverse the characteristic hair miniaturisation seen in this condition. When compared to results of published trials of standard therapy, ALRV5XR showed a multi-fold increase both in efficacy and in response rates. In addition, the continuance of TH regrowth from 12 to 24 weeks suggests that the normal structure and function of non-productive telogen follicles is restored and that a normal hair phenotype may be attained by extended ALRV5XR treatment.

Funding: Arbor Life Labs.

Keywords: ALRV5XR; Ageing; Alopecia; Androgenetic alopecia; Botanical; Clinical trial; Finasteride; Hair regeneration; Hair restoration; Male pattern hair loss; Minoxidil; PRP; Regenerative medicine; Senescence; Stem cell; Supplement; Terminal hair; Terminal vellus ratio; Vellus like hair; Vitamin; Wnt/beta-catenin.

Conflict of interest statement

PRF is the director of Arbor Life Labs (ALL), PRF, DJC and DB are coinventors of patent pending PCT/US2020/067585 titled Botanicals as Wnt/β-Catenin Activators, Molecular Pathway Regulators, Tissue Regenerators and Health Biomarker Regulators, filed for ALRV5XR and have a share in ALL. PRF, KMF, CP, BMM, DJC and JG, received honoraria from ALL and proposed submission for publication. DJC is an employee of ALL All authors had full access to the data in the study.

© 2021 The Author(s).

Figures

Fig. 1
Fig. 1
Profile of Randomised Controlled Trial. 79 subjects were assessed for eligibility which resulted in 19 subjects in the placebo group and 17 subjects in the ALRV5XR (treatment) group completing the trial and were included in the safety analysis. Evaluable subjects for primary efficacy analysis at 24 weeks resulted in 11 from the placebo group and 11 from the ALRV5XR group.
Fig. 2
Fig. 2
Sample Global Photographs and Corresponding Phototrichoscopy Computer Image Analysis at baseline, week 12 and week 24. Phototrichoscopy images for Subject: M013 were analysed with the TrichoSciencePro software (version 1.6): a: Baseline (BL) Global Frontal; b: BL Global Top; c: BL Global Vertex; d: BL Phototrichoscopy (PT); e: BL PT Processed (PR); f: BL PT PR & Tagged (TG); g: Week 12 (W12) PT Raw; h: W12 PT PR; i: W12 PT PR & TG; j: Week 24 (W24) PT Raw; k: W24 PT PRD; l: W24 PT PR & TG. This analysis resulted in the following sample measurements: Subject: M013; Sex: Male; Age: 34; Ethnicity: Hispanic; Ethnic Hair Type: Latin/Indian/Semitic; Fitzpatrick Skin Type: IV; Diagnosis: Androgenetic Alopecia; Hamilton-Norwood Class: IIIV; Trichoscopy Area of View: 42·19 mm2; Trichoscopy Magnification: 40x.
Fig. 3
Fig. 3
Changes in Terminal Hair Density from Baseline Over 24 Weeks. Treatment group ALRV5XR was statistically significantly superior to the placebo group for both (a) Absolute Change in Terminal Hairs: 21·0 THs/cm2 with an Odds Ratio (OR) of 87·4 [95% CI: 9·2–32·8; (p = 0·0014)] and (b) Per Cent Change in Terminal Hairs: 16·4% with an OR of 87·4 [95% CI: 7·4% – 25·5%; (p = 0·0012)]. Linear regressions are shown as lines with 95% confidence intervals shown in grey.
Fig. 4
Fig. 4
Changes in Vellus Hair Density from Baseline Over 24 Weeks. Treatment group ALRV5XR decreased statistically significantly to placebo group for both (a) Absolute Change in Vellus Hairs: −10·5 VHs/cm2 with OR 0·1 [95% CI: −1·9–−19·1; (p = 0·0196)] and (b) Per Cent Change in Terminal Hairs: −12·0% with OR 0·1 [95% CI: −2·5%–21·5%; (p = 0·0158)]. Linear regressions are shown as lines with 95% confidence intervals shown in grey.
Fig. 5
Fig. 5
Changes in Terminal to Vellus Hair Ratio from Baseline Over 24 Weeks. Treatment group ALRV5XR increased statistically significantly to the placebo group for both (a) Absolute Change in Terminal to Vellus Hair Ratio: 0·5 compared to placebo with OR of 81·0 [95% CI: 0·2–0·9; (p = 0·0097)] and (b) Per Cent Change in Terminal to Vellus Hair Ratio: 33·0% with an OR of 81·0 [95% CI: 12·5%–53·4%; (p = 0·0033)]. Linear regressions are shown as lines with 95% confidence intervals shown in grey.

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