Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000117617
Ethics application status
Approved
Date submitted
24/01/2023
Date registered
3/02/2023
Date last updated
12/07/2023
Date data sharing statement initially provided
3/02/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
A Multi-Centre, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Phase 1 Study to Evaluate the Safety, Tolerability and Pharmacokinetics of OLX72021 in Healthy Males with Androgenetic Alopecia.
Scientific title
A Multi-Centre, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Phase 1 Study to Evaluate the Safety, Tolerability and Pharmacokinetics of OLX72021 in Healthy Males with Androgenetic Alopecia.
Secondary ID [1] 308694 0
OLX72021-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Androgenetic Alopecia 328625 0
Condition category
Condition code
Skin 325628 325628 0 0
Dermatological conditions
Skin 325629 325629 0 0
Other skin conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a randomised, double-blind, placebo-controlled, single ascending dose treatment, multi-cohort study. Up to 30 healthy male volunteers with mild to severe androgenetic alopecia (AGA), aged 18 to 75 years of age (inclusive) at the time of screening will be enrolled in a total of 5 cohorts (Cohorts 1 to 5). The study will evaluate 5 dose levels of the investigational product, OLX72021, at the following dose levels:

• Cohort 1: 0.6 mg (0.1 mg/injection)
• Cohort 2: 3.0 mg (0.5 mg/injection)
• Cohort 3: 6.0 mg (1.0 mg/injection)
• Cohort 4: 7.2 mg (1.2 mg/injection)
• Cohort 5: 9.0 mg (1.5 mg/injection)

A single OLX72021 treatment will be administered as 6 intradermal injections to the scalp on study Day 1. Each dose level will be evaluated in a cohort of 6 participants with 4 participants receiving OLX72021 and 2 participants receiving placebo. Dosing in each cohort will start with 2 sentinel participants (1 participant will receive OLX72021 and the other will receive placebo). The safety and tolerability of each sentinel participant will be monitored until Day 2 prior to dosing the remainder of participants in each cohort.

The clinical facility staff will administer the study drug via intradermal injections to participants. Compliance will be monitored by site staff witnessing of dosing and documentation in participant study file. Dosing compliance will be recorded in study-specific patient diaries recording the date, time and dose administered.
Intervention code [1] 325159 0
Treatment: Drugs
Comparator / control treatment
Placebo (commercially available normal saline - 0.9%) will be identical in appearance to the investigational product and will be administered via intradermal injection.
Control group
Placebo

Outcomes
Primary outcome [1] 333477 0
To investigate the safety and tolerability of a single intradermal treatment of OLX72021 in healthy males with AGA.

Safety endpoints include:
Incidence, severity, and relationship of Adverse Events (AEs)/Serious Adverse Events (SAEs) (including withdrawals due to AEs)
Change from baseline in physical examination findings
Change from baseline in vital signs
Change from baseline in electrocardiogram (ECG) parameters
Change from baseline in clinical laboratory parameters (haematology, serum chemistry,
and urinalysis)
Local tolerability (site of intradermal injections)
Timepoint [1] 333477 0
Adverse events graded using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) (Version 5) and assessed continuously as they are reported or observed and reviewed during screening, Day -1, Day 1 through to Day 55 and Day 56 post-dose (End of Study) or Early Termination Visit.

Full physical examinations will include, at a minimum, assessment of the following: general appearance, head, ears, eyes, nose and throat, neck (including thyroid and lymph nodes), respiratory system, cardiovascular system, gastrointestinal system, renal system, neurological condition, musculoskeletal system, skin and any other focused assessments suggested by the presence of specific symptoms and will be conducted at Screening and Day 56 (End of Study) or Early Termination Visit.
Symptom directed Physical examination will be performed if clinically indicated, on Day 1 pre-dose, 2 hrs post-dose, Day 2 24 hrs post-dose, Day 3 48 hours post-dose, and at any time on Day 7, Day 14 and Day 28 post-dose.

Vital Signs (Blood pressure and heart rate is measured using a sphygmomanometer, respiratory rate using manual breath count and temperature by tympanic thermometer) and assessed at Screening, Day 1 pre-dose, 1 hr, 2 hrs, 4 hrs and 6 hrs post-dose, Day 2 24 hrs post-dose, Day 3 48 hrs post-dose, and at any time on Day 7, Day 14, Day 28 and Day 56 post-dose (End of Study) or Early Termination Visit.

12-Lead ECG: ECG recordings will be obtained in triplicate at Screening, Day -1, Day 1 pre-dose, 2 hrs and 6hrs post-dose.

Clinical Laboratory Evaluations (haematology, serum chemistry, coagulation and urinalysis) blood and urine samples collected at Screening, Day -1, Day 2 24 hrs post-dose, and at any time on Day 7, Day 14, Day 28 and Day 56 post-dose (End of Study) or Early Termination Visit.

Local tolerability: Tolerability at the treatment site will be assessed by an Investigator with dermatological expertise and assessed on Day 1 0.25 Hrs, 0.5 hrs, 1 hrs post-dose, and at any time on Day 2, Day 3, Day 7, Day 14, Day 28 and Day 56 post-dose (End of Study) or Early Termination Visit.
Secondary outcome [1] 417225 0
To measure the pharmacokinetics (PK) of OLX72021 in plasma following a single intradermal treatment in healthy males with AGA.

Plasma PK endpoints include (but are not limited to):
Maximum observed concentration (Cmax)
Time to Cmax (Tmax)
Area under the concentration-time curve from 0 to time of last quantifiable concentration (AUC0-t)
Area under the concentration-time curve from 0 to infinity (AUC0-inf)
Apparent terminal elimination half-life (t1/2)
Terminal elimination rate constant (Lambda z)
Total apparent body clearance (CL/F)
Apparent volume of distribution (Vz/F)
Timepoint [1] 417225 0
Plasma PK samples collected at the following timepoints: within 15 mins pre-dose Day 1, 1 hr, 3hrs, 6 hrs post-dose, Day 2 24 hrs post-dose, Day 3 48 hrs post-dose.
Secondary outcome [2] 417226 0
Exploratory Objective: To measure the pharmacodynamic effects of OLX72021 following a single intradermal treatment in healthy males with AGA.

Pharmacodynamic endpoint:
Protein levels of Androgen Receptor in punch biopsy samples.
Timepoint [2] 417226 0
Punch biopsy samples will be collected during screening following confirmation of study eligibility at least 14 days prior to OLX72021 administration and on Day 28 post-dose.
Secondary outcome [3] 417227 0
Exploratory Objective: To investigate the potential effects of a single OLX72021 intradermal treatment on sexual function.

Endpoints include Sexual disfunction effects (international index of erectile function (IIEF-5) questionnaire).
Timepoint [3] 417227 0
International index of erectile function (IIEF-5) questionnaire to be completed pre-dose Day 1, Day 28 and Day 56 post-dose (End of Study) or Early Termination Visit.

Eligibility
Key inclusion criteria
1. Must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects.
2. Generally healthy with the exception of those medical conditions allowed as per the inclusion/exclusion criteria
3. Adult males, 18 to 75 years of age (inclusive) at screening, with mild to severe AGA of Norwood-Hamilton Classification score of 3 vertex to 7 with no other aetiology of hair loss (e.g. alopecia areata, scarring alopecia, telogen effluvium)
4. Body mass index greater than or equal to 18.0 and less than or equal to 30.0 kg/m2, with a body weight (to 1 decimal place) greater than or equal to 50 kg at screening.
5. Be non-smokers (including tobacco, e-cigarettes and marijuana) for at least 3 months prior to first study drug administration and have a negative test for cotinine at the screening visit and on the day of treatment (Day 1).
6. Medically healthy without clinically significant abnormalities (in the opinion of the Investigator) at the screening visit and prior to dosing at the timepoints indicated in the Schedules of Assessments including:
a. Physical examination without any clinically significant findings;
b. Systolic blood pressure in the range of 90 to 140 mmHg (inclusive) and diastolic blood pressure in the range of 40 to 90 mmHg (inclusive) after 5 minutes in supine (or semi-supine) position;
c. Heart rate (HR) in the range of 40 to 100 bpm (inclusive) after 5 minutes rest in supine (or semi-supine) position;
d. Body temperature (tympanic or oral) in the range 35.5°C to 37.5°C (inclusive);
e. No clinically significant findings in serum chemistry, haematology, coagulation, and urinalysis tests;
f. Triplicate 12-lead ECG (taken after the volunteer has been supine (or semi-supine) for at least 10 minutes) with a QT interval corrected using the Fridericia method (QTcF) less than or equal to 450 msec and no clinically significant abnormalities.
7. If not surgically sterilised, must agree to:
a. Not donate sperm after signing consent, during the study, and at least 90 days after the last dose of study drug;
b. If engaging in sexual intercourse with a female partner who could become pregnant, use a condom in addition to having the female partner use a highly effective contraceptive method.
8. Have suitable venous access for blood sampling.
9. Be willing and able to comply with all study assessments and adhere to the protocol schedule and restrictions including:
a. Undergo 2 punch biopsies of the scalp during the study
b. Receive a small non-permanent scalp tattoo dot, which may be re-applied throughout the study
c. Maintain the same hair style and length as at the start of the study for the duration of the study
d. Avoid semi-permanent hair products (e.g., colour, texturisers, relaxers) for the duration of the study [NOTE: use of daily styling products (e.g., hair gel, mousse, styling spray) are permitted on non-study visit days]
e. Use non-medicated shampoo and conditioner for the duration of the study (or Sponsor-supplied shampoo and conditioner in place of regular shampoo and conditioner, for the duration of the study). NOTE: use of Sponsor-supplied conditioner is optional for participants who do not use conditioner
Minimum age
18 Years
Maximum age
75 Years
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
1. History or presence of significant cardiovascular, pulmonary, hepatic, renal, haematological, gastrointestinal, endocrine, immunologic, dermatologic or neurological disease, including any acute illness or major surgery within the past 3 months determined by the PI to be clinically significant (participants with resolved childhood asthma may be included in the study).
2. Any of the following clinically significant disease:
a. uncontrolled chronic diseases other than AGA (e.g., diabetes mellitus, hypertension, liver disease)
b. thyroid disease (hyperthyroidism, hypothyroidism) (NOTE: history of controlled thyroid disease > 12 weeks prior to administration of study treatment is not exclusionary)
3. History of clinically significant heart disease (e.g., ischemic heart disease, arrhythmia) within 24 weeks prior to the start of study treatment
4. History of risk factors for torsade de pointes (including a family history of long QT syndrome or sudden cardiac death) or a known arrythmia.
5. Any dermatological disorders of the scalp which might interfere with the application of investigational product (IP) or examination method, such as fungal or bacterial infections, seborrheic dermatitis, psoriasis, eczema, folliculitis or scalp atrophy
6. History or clinical signs of keloids or hypertrophic scars
7. History of active hair loss due to alopecia areata, scarring alopecia, diffuse telogen effluvium or conditions other than AGA
8. History of surgical correction of hair loss on the scalp
9. History of hair transplants
10. Current use of an occlusive wig, hair extensions or hair weaves
11. Use of topical treatments (minoxidil, anti-androgens, platelet rich plasma [PRP] or other agents known to affect hair growth) or devices (e.g., laser light therapy), purposed to promote scalp hair growth, within 12 weeks prior to administration of study treatment (NOTE: use of cosmeceuticals is not exclusionary if used > 2 weeks prior to administration of study treatment)
12. Use of the following medications within 24 weeks prior to the first administration of study treatment:
a. Minoxidil
b. Dutasteride, finasteride
c. Androgenic agent (e.g., anabolic steroid)
d. Anti-androgenic therapies (e.g., spironolactone, flutamide, cyproterone acetate, cimetidine, ketoconazole) (NOTE: topical use is not exclusionary if used > 12 weeks prior to administration of study treatment)
e. Medications that potentially cause hypotrichosis (e.g., depotestosterone, haloperidol, methotrexate, methylprednisolone, prednisone, testosterone, divalproex sodium, heparin, coumarin, carbamazepine, valproic acid, lithium)
f. Medications that potentially cause hypertrichosis (e.g., cyclosporine, diazoxide, phenytoin, psoralens, phenothiazines)
13. Anti-cancer agents, including cytotoxic agents, that can potentially have effects on alopecia within 12 months prior to the first administration of study treatment
14. Scalp hair loss on the treatment area, due to disease, injury or medical therapy
15. Current infection that requires systemically absorbed antibiotic, antifungal, antiparasitic or antiviral medications.
16. Any history of malignant disease in the last 5 years (excludes surgically resected skin squamous cell or basal cell carcinoma).
17. Presence of clinically relevant immunosuppression from, but not limited to, immunodeficiency conditions such as common variable hypogammaglobulinemia.
18. Use of or plans to use systemic immunosuppressive (e.g., corticosteroids, methotrexate, azathioprine, cyclosporine) or immunomodulating medications (e.g., interferon) during the study or within 3 months prior to the first study drug administration (prior use of nasal sprays for hayfever may be permitted at the discretion of the PI; use of inhaled steroids for asthma is not exclusionary).
19. Liver function test results elevated more than 1.5-fold above the upper limit of normal (ULN) for gamma glutamyl transferase (GGT), bilirubin (total, conjugated and unconjugated), alkaline phosphatase (ALP), aspartate aminotransferase (AST) or alanine aminotransferase (ALT). Volunteers with ALP and/or ALT/AST above the limits specified may be included, at the discretion of the Investigator, if the levels are unaccompanied by clinical signs and are determined to be normal variants.
20. Estimated creatinine clearance (CrCl) < 60 mL/min/1.73m squared or serum creatinine more than 1.5-fold above the ULN.
21. Positive test results for active human immunodeficiency virus (HIV-1 or HIV-2), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies at the screening visit.
22. History of substance abuse or alcohol abuse within 12 weeks prior to the screening visit (defined as more than an average of 14 standard drinks per week or regular consumption of more than 4 standard drinks on any one day; where 1 standard drink is 10 g of pure alcohol and is equivalent to 285 mL beer [4.9% Alc./Vol], 100 mL wine [12% Alc./Vol], 30 mL spirit [40% Alc./Vol]).
23. Positive drugs of abuse or alcohol breath test results at the screening visit or on the day of treatment (Day 1).
24. Use of any prescription or over-the-counter medication (including herbal products, and hormone supplements) within 10 days or 5 half-lives of the medication (whichever is longer) prior to the first study drug administration – exceptions include occasional use of paracetamol (doses of 500 mg up to every 6 hours or 2 g per day maximum for no more than 3 consecutive days), ibuprofen (doses of 400 mg up to every 6 hours or 1.2 g per day maximum for no more than 3 consecutive days), topical ointments, and vitamins or dietary supplements.
25. Demonstrated clinically significant (required intervention, e.g., emergency room visit, epinephrine administration) allergic reactions (e.g., food, drug, or atopic reactions, asthmatic episodes) which, in the opinion of the Investigator, would interfere with the volunteer’s ability to participate in the trial
26. Use of any vaccinations within 14 days prior to the first study drug administration.
27. Male participants with female partners of childbearing potential who are planning to become pregnant or do not agree to use one or more of the clinically appropriate methods of contraception from the first day of study participation until 90 days following the last administration of study treatment.
28. Donation of blood or plasma within 30 days prior to first study drug administration, or loss of whole blood of more than 500 mL within 30 days prior to first study drug administration, or receipt of a blood transfusion within 1 year of first study drug administration.
29. Treatment with an investigational drug in another clinical trial within 60 days or 5 half-lives of the other investigational drug (whichever is longer) prior to the first administration of study drug in this trial.
30. Any other condition or prior therapy that in the opinion of the Investigator would make the volunteer unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
All study participants who sign an informed consent form at screening will receive a unique
sequential number (i.e., a Screening Number). Participants who meet the study eligibility criteria will be assigned a randomisation number pre-dose on Day 1, which corresponds to a study treatment (OLX72021 or placebo).
As the study is double-blinded, sealed participant-specific code break envelopes will be produced by the unblinded study statistician(s) and will be retained at the clinical facility in a secure, accessible location.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The allocation to OLX72021 or placebo will be performed using a block randomisation algorithm and will be documented in the study randomisation schedule.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Other
Other design features
The study will evaluate 5 dose levels of the investigational product, OLX72021, in 5 cohorts of 6 participants per cohort. In each cohort, 4 participants will receive the investigational product and 2 participants will receive placebo. Evaluation of dose levels will be conducted in a sequential fashion with lower dose levels evaluated first in the sequence.

The decision to escalate between dose levels will be based on review of participant safety and PK data available following study assessments on Day 14. Safety and PK data will be assessed by the study Safety Review Committee (SRC) who will make recommendations in relation to study progression.
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
This study is the First in Human (FIH) study with OLX72021 and as such no formal sample size calculation was performed. The chosen sample size is deemed adequate to evaluate all study endpoints.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/06/2023
Actual
5/06/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
30
Accrual to date
1
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,VIC
Recruitment hospital [1] 23772 0
Woden Dermatology - Phillip
Recruitment hospital [2] 24712 0
Emeritus Research - Camberwell
Recruitment hospital [3] 24713 0
Emeritus Research - Botany - Botany
Recruitment hospital [4] 24714 0
Veracity Clinical Research - Woolloongabba
Recruitment postcode(s) [1] 40332 0
2019 - Botany
Recruitment postcode(s) [2] 39217 0
2606 - Phillip
Recruitment postcode(s) [3] 40331 0
3124 - Camberwell
Recruitment postcode(s) [4] 40333 0
4102 - Woolloongabba
Recruitment outside Australia
Country [1] 25372 0
New Zealand
State/province [1] 25372 0
Takapuna, Auckland

Funding & Sponsors
Funding source category [1] 312923 0
Commercial sector/Industry
Name [1] 312923 0
OliX Pharmaceuticals, Inc.
Country [1] 312923 0
Korea, Republic Of
Primary sponsor type
Commercial sector/Industry
Name
OLIX AU PTY LTD
Address
Suite 402/ 15 Blue Street, North Sydney NSW, 2060, Australia
Country
Australia
Secondary sponsor category [1] 314601 0
Commercial sector/Industry
Name [1] 314601 0
Avance Clinical Pty Ltd
Address [1] 314601 0
213 Glynburn Road, Firle SA 5070
Country [1] 314601 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312195 0
Bellberry Limited Human Research Ethics Committee
Ethics committee address [1] 312195 0
123 Glen Osmond Road, Eastwood SA 5063
Ethics committee country [1] 312195 0
Australia
Date submitted for ethics approval [1] 312195 0
21/12/2022
Approval date [1] 312195 0
08/03/2023
Ethics approval number [1] 312195 0
Ethics committee name [2] 312748 0
Health and Disability Ethics Committees (HDEC)
Ethics committee address [2] 312748 0
133 Molesworth Street, Thorndon, Wellington 6011
Ethics committee country [2] 312748 0
New Zealand
Date submitted for ethics approval [2] 312748 0
24/03/2023
Approval date [2] 312748 0
Ethics approval number [2] 312748 0

Summary
Brief summary
This is a randomised, double-blind, placebo-controlled, single ascending dose treatment, multi-cohort study. The study will evaluate 5 dose levels of the investigational product, OLX72021, in 5 cohorts. Dose levels will be evaluated in a sequential manner starting at the lowest dose level.

Healthy male volunteers with mild to severe androgenetic alopecia (AGA), aged 18 to 75 years of age (inclusive) at the time of screening are eligible for recruitment.

The total maximum study duration for participants in this study is 87 days (approx. 12 weeks). This includes a screening period (Day -28 to Day -14) and 56 days (± 3 days) post-treatment follow-up.

Androgenetic alopecia has been linked to an imbalance of androgen hormones. OLX72021 is designed to target the androgen receptor (AR) gene, leading to reduced AR protein expression in the body. Because androgenetic alopecia could be caused by an imbalance of androgens, blocking the AR gene helps to reduce these harmful responses and allow hair growth to return to normal. The information learned from this study may help future participants with androgenetic alopecia.
Trial website
Trial related presentations / publications
Public notes
Exclusion Criteria:
28. Use of any vaccinations within 14 days prior to the first study drug administration (vaccination for Covid-19 is permitted at any time prior to first study drug administration).

Contacts
Principal investigator
Name 123810 0
Dr Diana Marie Rubel
Address 123810 0
Paratus Clinical Research Woden
Level 1, 1 Bowes Place, Phillip,
Australian Capital Territory
Australia 2606
Country 123810 0
Australia
Phone 123810 0
+61 2 6282 8410
Fax 123810 0
Email 123810 0
diana@wodendermatology.com.au
Contact person for public queries
Name 123811 0
Mr Hayden Ellis
Address 123811 0
Paratus Clinical Research Woden
Level 1, 1 Bowes Place, Phillip,
Australian Capital Territory
Australia 2606
Country 123811 0
Australia
Phone 123811 0
+61 1300 742 326
Fax 123811 0
Email 123811 0
hayden.ellis@paratusclinical.com
Contact person for scientific queries
Name 123812 0
Dr Diana Marie Rubel
Address 123812 0
Paratus Clinical Research Woden
Level 1, 1 Bowes Place, Phillip,
Australian Capital Territory
Australia 2606
Country 123812 0
Australia
Phone 123812 0
+61 2 6282 8410
Fax 123812 0
Email 123812 0
diana@wodendermatology.com.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Privacy and intellectual property considerations


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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