A Study Evaluating the Hair Regrowth Efficacy and Safety of ALRV5XR in Male Subjects With Hair Loss
Condition: Androgenetic Alopecia; Androgenic Alopecia; Telogen Effluvium; Thinning Hair; Hair Loss/Baldness; Hair Thinning
MeSH terms: Alopecia; Alopecia Areata; Hypotrichosis
Study type: Interventional

Summary: 
      To demonstrate that the ALRV5XR multi-molecular targeting treatment regimen of a daily
      shampoo, conditioner, topical serum and oral supplement is superior to placebo in promoting
      hair growth as assessed by change in hair density and percentage of terminal hair regrowth
      after ALRV5XR therapy.

      This will be a single-centre, double-blind, randomized, placebo-controlled study in male
      subjects randomized to a 1:1 ratio of test article to placebo.

      Subjects will be asked to use the study products on a daily basis for the duration of the
      24-week study. Subjects will take one capsule twice daily (one in the morning and one in the
      evening) and will be asked to use 3-7mL of the shampoo, 3-7mL of the conditioner, and 1mL of
      the topical nutriment daily. Subjects will receive detailed instructions regarding the order
      and duration of application of each product.

      Subjects in the active arm will receive active capsules, shampoo, conditioner and topical
      nutriment. Subjects on placebo will receive placebo capsules, shampoo, conditioner and
      topical nutriment. All subjects will be instructed to take the capsules orally, one in the
      morning and one in the evening, prior to consuming food. Shampoo and conditioner are to be
      used once per day when washing the hair and nutriment applied at the end of the day prior to
      bedtime. To facilitate this, subjects will receive a 3-month supply of each product
      (supplement, shampoo, conditioner, and scalp nutriment). Subjects will continue the daily
      regimen for 24 weeks, visiting the clinic at week 12 for an interim assessment.
    

Detailed description: 
      This is a prospective, randomized, double-blind, placebo-controlled, 2-arm parallel study to
      evaluate the efficacy and safety of a multi-molecular targeting botanical treatment regimen
      on parameters of hair growth, compared to placebo, in healthy male adults with androgenetic
      alopecia, diffuse hair loss or self-reported thinning hair.

      Each study group will include 23 subjects. Subjects will be randomly assigned using computer
      generated randomization scheme to one of the two groups in a 1:1 ratio.

      Subjects will be asked to use the study products on a daily basis for the duration of the
      24-week study. Subjects will take one capsule twice daily (one in the morning and one in the
      evening) and will be instructed to use 3-7mL of the shampoo, 3-7mL of the conditioner, and
      1mL of the topical nutriment serum daily. Subjects will receive detailed instructions
      regarding the order, and duration of application of each product.

      This trial will be conducted at one (1) American (USA) clinical research site. The duration
      of the study will be approximately 28 weeks (7 months), including the screening period. There
      will be a screening period of up to 28 days for eligibility assessment, followed by a
      baseline visit followed by a 24-week experimentation period for assessment of supplement
      effects. There will be a total of seven visits, including a screening visit, over this
      28-week period.

      The study will be conducted as outlined in this protocol and in compliance with the
      principles of the International Conference on Harmonization (ICH) Guidelines on Good Clinical
      Practice (GCP) (E.6), and the Declaration of Helsinki.

      Prior to initiating any study-related procedures, each subject must provide written informed
      consent in accordance with Institutional Research Board (IRB) requirements and applicable
      regulations. Any potential subject will be contacted by a designated member of the research
      team at the study site. Potential subjects may complete a web-based pre-screening
      questionnaire or may be interviewed. During the interview (or web-based questionnaire),
      subjects will answer specific questions, in order to assess their eligibility. If they meet
      pre-screening requirements, they will be invited to schedule a screening visit (Visit 1) with
      a Study Coordinator no more than 30 days prior to the anticipated baseline visit (Visit 2).
      In the event that subjects' screening period exceeds 30 days, the Investigator may repeat
      blood work, biometrics and/or vital signs (as appropriate) to ensure that subjects remain
      eligible.

      Visit 1 (Screening Visit):

      At the screening visit (Visit 1), up to 30 days prior to the Baseline Visit (Visit 2), the
      overall details of the study and the procedures to be undertaken will be explained to the
      subject. The following information will be recorded and procedures carried out:

        -  Subject registration

        -  Informed Consent (copy to subject)

        -  Subject education/comprehension questionnaire

        -  Review inclusion & exclusion criteria

        -  Assess Fitzpatrick phototype skin classification

        -  Demographic data (dietary habits, race, ethnicity, age, etc.)

        -  Medical history

        -  Concomitant medications recorded

        -  Measure screening anthropometrics and vital signs: height (cm), weight (kg), temperature
           (°C) respiratory rate (breaths/min), blood pressure (mmHg) and heart rate (bpm).

        -  Calculate BMI (kg/m2)

        -  Scalp examination (including photographs) for each subject will include a screen for
           immediately observable medical issues and any scalp alopecia/scalp disorders;
           photography of hair (top, right side, left side, back) - photographs will be shared with
           the Sponsor for determination of eligibility to participate in the study.

        -  Physical examination (excluding breast, genital and anorectal exam)

        -  Collect fasting (>6h, nothing to eat or drink except water) blood for screening
           laboratory tests

        -  Provide the subject with an instruction handout explaining visit preparation and overall
           study requirements (provide written and verbal instructions).

      Remind subjects to follow inclusion/exclusion criteria of restrictions for both OTC and
      prescription medications, maintain current dietary habits, sleep habits, exercise and sexual
      intercourse habits.

      If the subject is eligible for the study, they will be given a date to attend the Site no
      more than 30 days after the screening visit.

      Visit 2 (Baseline Visit) - Day 0 Inclusion/Exclusion Criteria will be re-assessed to ensure
      eligibility. Concomitant medications and adverse events (AE's) will be reviewed. Eligible
      subjects will be randomized to one of the two treatment arms.

      The following procedures will be completed prior to dosing:

        -  Monitor adverse events (since the previous visit)

        -  Review concomitant medications

        -  Measure anthropometrics and vital signs: weight (kg), temperature (°C) respiratory rate
           (breaths/min), blood pressure (mmHg) and heart rate (bpm)

        -  Calculate BMI (kg/m2)

        -  Review inclusion & exclusion criteria

        -  Scalp examination (including photographs) for each subject will include a screen for
           observable medical issues and any skin/scalp disorders; photography of hair (top, right
           side, left side, back) - photographs will be reviewed and SALT score determined by a
           dermatologist. General photographic instructions are described in APPENDIX III.

        -  Subjects will be asked to complete the Dermatology Quality of Life Index (DQLI)

        -  Use Trichology device to capture images of scalp target area for efficacy assessments

        -  Randomize eligible subjects

        -  Provide subject with the first dose of the oral supplement in clinic

      The following procedures will be completed after dosing:

        -  Monitor subject for any immediate reactions (minimum 15-minute observation post-
           administration)

        -  Dispense 3-month supply of investigational product

        -  Provide subjects with instruction for using kit contents

        -  Remind subjects to follow inclusion/exclusion criteria for restrictions for both OTC and
           prescription medications, maintain current dietary habits, sleep habits, exercise and
           sexual intercourse habits.

        -  Provide subjects with a diary to record product use and any changes to health status or
           medication use

      Visit 3 (Return for anagen/telogen ratio assessment) - day 3 Subjects will return to the
      clinic on day 3 to have the baseline anagen/telogen ratio assessed.

      Visit 4 (Interim Visit) - Day 84 Study subjects will return to the Clinic on Day 84.

      The following procedures will be completed:

        -  Collect daily diaries and review

        -  Collected investigational product containers (used and unused) and assess compliance

        -  Monitor adverse events (since the previous visit)

        -  Review concomitant medications (including changes to medications, changes to dose and
           frequency)

        -  Measure anthropometrics and vital signs: weight (kg), temperature (°C) respiratory rate
           (breaths/min), blood pressure (mmHg) and heart rate (bpm)

        -  Calculate BMI (kg/m2)

        -  Scalp examination (including photographs) for each subject will include a screen for
           observable medical issues and any skin/scalp disorders; photography of hair (top, right
           side, left side, back) - photographs will be reviewed and SALT score determined by a
           dermatologist.

        -  Subjects will be asked to complete the Dermatology Quality of Life Index (DQLI)

        -  Use Trichology device to capture images of scalp target area for efficacy assessments

        -  Collect blood for safety laboratory tests

        -  Dispense 3-month supply of investigational product

        -  Provide subjects with instruction for using kit contents

        -  Remind subjects to follow inclusion/exclusion criteria for restrictions for both OTC and
           prescription medications, maintain current dietary habits, sleep habits, exercise and
           sexual intercourse habits

        -  Provide subjects with a diary to record product use and any changes to health status or
           medication use

        -  Subjects will be booked for their next appointment

      Visit 5 (Return for anagen/telogen ratio assessment) - day 87 Subjects will return to the
      clinic to have the anagen/telogen ratio assessed.

      Visit 6 - Day 168 Study subjects will return to the Clinic on Day 168.

      The following procedures will be completed:

        -  Collect daily diaries and review

        -  Collected investigational product containers (used and unused) and assess compliance

        -  Monitor adverse events (since the previous visit)

        -  Review concomitant medications (including changes to medications, changes to dose and
           frequency)

        -  Measure anthropometrics and vital signs: weight (kg), temperature (°C) respiratory rate
           (breaths/min), blood pressure (mmHg) and heart rate (bpm)

        -  Calculate BMI (kg/m2)

        -  Scalp examination (including photographs) for each subject will include a screen for
           observable medical issues and any skin/scalp disorders; photography of hair (top, right
           side, left side, back) - photographs will be reviewed and SALT score determined by a
           dermatologist.

        -  Subjects will be asked to complete the Dermatology Quality of Life Index (DQLI)

        -  Use Trichology device to capture images of scalp target area for efficacy assessments

        -  Collect blood for safety laboratory tests

      Visit 7 (Return for anagen/telogen ratio assessment and end of study assessment) - day 171
      Subjects will return to the clinic on day 3 to have the baseline anagen/telogen ratio
      assessed.

      Early Termination/Discontinuation Visit

      Subjects may elect to independently withdraw from participation in the study at any time. At
      a termination visit, subjects will be encouraged to undergo the procedures specified in the
      final study visit. Reasons for early termination/ discontinuation may include the subject
      developing any condition which contravenes the original criteria, or, at the discretion of
      the Principal Investigator (PI), the subject is considered to be unsuitable to continue the
      study. Individual subjects may have administration temporarily interrupted at the discretion
      of the PI, e.g. for AEs that are subsequently resolved. Subjects MUST have permanent
      discontinuation in the following situations:

        -  The subject had a Grade 3 (severe) or an investigational product-related SAE as
           determined by the PI

        -  Subject withdraws consent or refuses further assessment during the study

        -  Participation in another clinical trial

        -  Subject lost to follow-up

        -  Death

        -  Protocol violation

      Unscheduled Visits Any study participant who contacts the investigation site about possible
      adverse events that are more than minor and/or that persist will be asked to visit the
      research centre for an assessment as appropriate.

      Safety Tests Blood will be collected at V1, V4 and V6 for analysis of safety parameters.
      Anthropometrics and vital signs are being recorded at study visits number 1, 4, and 6 as
      measures of safety. Additionally, safety will be assessed by means of reported AEs.

      Stopping Rules/Discontinuation The Investigator may withdraw any subject from this research
      if circumstances arise that warrant doing so. If a subject is withdrawn from the study for
      any reason, they will be asked to complete an early termination visit.

      Permitted/Concomitant Medication(s) Subjects will be questioned about their medication
      history. The details of any medication taken will be recorded in the case notes and
      electronic Case Report Form (eCRF). Prescription and over-the-counter (OTC) medications
      (including supplements) not known to affect study endpoints are permitted.

      Thyroid medications will be permitted where dosage has been stable for 6 months prior to the
      screening visit (V1) and subjects are not expected to have a dosage change during the study
      period.

      Prohibited Medication(s)

      Medications that are prohibited include:

        -  Anabolic steroids in prior 6 months and during the clinical study period

        -  5-alpha reductase inhibitors in prior 6 months and during the clinical study period

        -  Products (including natural health products) and/or devices to promote scalp hair growth
           (e.g. finasteride, minoxidil, etc.) in 30 days prior to baseline (V2) and during the
           clinical study period

        -  Medications that are known to potentially cause hair loss or affect growth as determined
           by PI in 30 days prior to baseline (V2) and during the clinical study period

        -  Use of coagulation inhibiting medications (including natural health products) during the
           clinical study period

        -  Use of blood pressure lowering medications during the clinical study period

        -  Use of anti-inflammatory medications, corticosteroids or immunosuppressive drugs taken
           for more than 2 consecutive weeks in the 3 months prior to baseline (V2) and during the
           clinical study period

      Rescue Medication(s) As this study is investigating the effects of a product in a healthy
      population, there are no rescue medications in this study.

      SELECTION AND WITHDRAWAL OF SUBJECTS NUMBER OF STUDY PARTICIPANTS It is estimated that up to
      70 subjects will be screened, in order to identify 46 suitable subjects.

      WITHDRAWAL CRITERIA Subjects may withdraw from participation in a study at any time without
      consequence. If a subject withdraws from the study, the PI will make a reasonable effort to
      determine the reason for withdrawal from the study, which will be recorded on the eCRF, as
      will any AEs experienced by the subject.

      Personal reasons (Subject-initiated): Participation in the study is optional, and a subject
      can withdraw from the study at any time, without consequence or prejudice.

      Clinical judgment of PI: A subject could also be withdrawn from the study if, in the opinion
      of the PI, it is not in the subject's best interest to continue (e.g. AEs, need for
      prohibited medication, illness, etc.). All serious AEs (SAEs) will result in withdrawal from
      the trial.

      Protocol violation: If a subject fails to comply with the protocol they may be removed at the
      discretion of the PI.

      Reasons for withdrawal will be documented as one of the following:

      W.1 Subject requests withdrawal from the study. W.2 Subject withdraws consent. W.3 AE makes
      the continuation of the subject in the study impossible or inadvisable.

      W.4 Subject was incorrectly included in the study (discovered after enrollment not to have
      met the protocol entrance criteria). W.5 Subject is not complying with required study
      procedures.
    

Intervention name(s): ALRV5XR; ALRV5XR Shampoo; ALRV5XR Conditioner; ALRV5XR Hair Follicle Serum (Nutriment); Placebo; Placebo Shampoo; Placebo Conditioner; Placebo Hair Follicle Serum (Nutriment)
Intervention type(s): Dietary Supplement; Other; Other; Other; Dietary Supplement; Other; Other; Other
Intervention description(s): ALRV5XR oral supplement. Dose/Route/Schedule: 1 capsule/oral twice daily. Take one capsule in the morning and one capsule in the evening. Take 30-60 minutes before food. If stomach upset occurs, subjects will be instructed to take the capsule at the beginning of a meal.
There should be no deviation from the daily nutriment regimen (although in the event a capsule or day is missed, subject should continue with regimen the following day.); ALRV5XR Shampoo. Dose/Route/Schedule: 3-7 ml, topical, daily. The amount of shampoo used will vary by subject, based on length of hair. Short hair will use approximately 3ml of shampoo per wash and long hair as much as 7 ml. For short hair, an amount equivalent to a quarter in the palm of a hand, and for long hair a half-dollar size.
There should be no deviation from the daily nutriment regimen (although in the event a day is missed, subject should continue with regimen the following day; ALRV5XR Conditioner. Dose/Route/Schedule: 3-7 ml, topical, daily. The amount of conditioner used will vary by subject based on length of hair. Short hair will use approximately 3ml of conditioner per wash and long hair as much as 7 ml. For short hair, an amount equivalent to a quarter in the palm of a hand, and for long hair a half-dollar size.
There should be no deviation from the daily nutriment regimen (although in the event a day is missed, subject should continue with regimen the following day; ALRV5XR topical Hair Follicle serum (Nutriment), sealed in an airless pump dispensing bottle, metered at 0.2ml per depression. Dose/Route/Schedule: 1ml, topical, daily, applied at night.
Topical serum (referred to as the Nutriment) dosage is metered as 5 x depressions of plunger per day to cover areas of thinning scalp and adjacent scalp areas. Care should be taken to limit the Nutriment in hair. Each depression is metered at 0.2ml for a daily dose of 1.0 ml. Each container has 30ml of Nutriment. Nutriment will dry within a few minutes and any on the hair will also dry. The dried effect in the hair should not cause oiliness or dryness on scalp or hair. There should be no deviation from the daily nutriment regimen (although in the event a day is missed, subject should continue with regimen the following day.); Placebo oral supplement. Dose/Route/Schedule: 1 capsule/oral twice daily. Take one capsule in the morning and one capsule in the evening. Take 30-60 minutes before food. If stomach upset occurs, subjects will be instructed to take the capsule at the beginning of a meal.
There should be no deviation from the daily nutriment regimen (although in the event a capsule or day is missed, subject should continue with regimen the following day.); Placebo Shampoo. Dose/Route/Schedule: 3-7 ml, topical, daily. The amount of shampoo used will vary by subject, based on length of hair. Short hair will use approximately 3ml of shampoo per wash and long hair as much as 7 ml. For short hair, an amount equivalent to a quarter in the palm of a hand, and for long hair a half-dollar size.
There should be no deviation from the daily nutriment regimen (although in the event a day is missed, subject should continue with regimen the following day; Placebo Conditioner. Dose/Route/Schedule: 3-7 ml, topical, daily. The amount of conditioner used will vary by subject based on length of hair. Short hair will use approximately 3ml of conditioner per wash and long hair as much as 7 ml. For short hair, an amount equivalent to a quarter in the palm of a hand, and for long hair a half-dollar size.
There should be no deviation from the daily nutriment regimen (although in the event a day is missed, subject should continue with regimen the following day; Placebo topical Hair Follicle serum (Nutriment), sealed in an airless pump dispensing bottle, metered at 0.2ml per depression. Dose/Route/Schedule: 1ml, topical, daily, applied at night.
Topical serum (referred to as the Nutriment) dosage is metered as 5 x depressions of plunger per day to cover areas of thinning scalp and adjacent scalp areas. Care should be taken to limit the Nutriment in hair. Each depression is metered at 0.2ml for a daily dose of 1.0 ml. Each container has 30ml of Nutriment. Nutriment will dry within a few minutes and any on the hair will also dry. The dried effect in the hair should not cause oiliness or dryness on scalp or hair. There should be no deviation from the daily nutriment regimen (although in the event a day is missed, subject should continue with regimen the following day.)
Other intervention name(s): Replenology; Replenology Hair; 21 To Grow; Nutrient Replenishment Biology; Replenology Hair Professional; Replenology Professional; Replenology Restore; Replenology; Replenology Hair; Replenology Shampoo; Nutrient Replenishment Biology; 21 To Grow; Replenology Retain; Replenology; Replenology Hair; Replenology Conditioner; Nutrient Replenishment Biology; 21 To Grow; Replenology Reinforce; Replenology; Replenology Follicle Nutriment; Replenology Hair; Nutrient Replenishment Biology; 21 To Grow; Replenology Revitalize; Replenology Scalp Serum
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Subjects will be randomized into 1 of 2 parallel groups. There will be one (1) treatment group and one (1) placebo group. Subjects will receive either the ALRV5XR treatment regimen or placebo regimen.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Androgenetic Alopecia; Androgenic Alopecia; Alopecia; Androgenetic; Androgenic; Telogen; Telogen Effluvium; Hair Loss; Baldness; Male Patterned Balding; Aging; Ageing; Senescence; Wnt; Wnt Beta-catenin Signaling Pathway; Stem Cell