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Trial registered on ANZCTR


Registration number
ACTRN12624000746538
Ethics application status
Approved
Date submitted
1/05/2024
Date registered
17/06/2024
Date last updated
28/07/2024
Date data sharing statement initially provided
17/06/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 2, Proof-of-concept, Multi-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of AT-5214 in Subjects with Moderate to Severe Facial Acne Vulgaris
Scientific title
A Phase 2, Proof-of-concept, Multi-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of AT-5214 in Subjects with Moderate to Severe Facial Acne Vulgaris
Secondary ID [1] 310364 0
AT-5214-203
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acne vulgaris 331101 0
Condition category
Condition code
Skin 327888 327888 0 0
Dermatological conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a multi centre, double-blind, randomized, placebo-controlled proof-of-concept trial to evaluate the efficacy and safety of AT-5214 in participants with moderate to severe acne vulgaris.

Approximately 100 participants will be randomized in a 1:1 ratio to receive either AT-5214 oral tablet or an identical placebo oral tablet. Eligible participants who withdraw before the start of treatment will be replaced.

Participants will receive oral AT-5214 or placebo tablets, 4 mg twice daily (BID) for 12 weeks. Participants will be provided with a diary card which they will be trained to use to record daily administration of the study drug. Compliance with the study treatment will be measured by return of unused drugs at the end of the treatment period (12 weeks).
Intervention code [1] 326760 0
Treatment: Drugs
Comparator / control treatment
Study participants randomized to receive placebo will take the placebo twice a day in an identical manner to the study drug AT-5214.
The placebo product is matched visually to the active study drug. It is equal in size, shape, and appearance to the drug product using the same excipients but contains no active drug substance. The placebo tablet contains microcrystalline cellulose, hydroxypropyl cellulose, croscarmellose sodium, colloidal silicon dioxide and magnesium stearate.
Control group
Placebo

Outcomes
Primary outcome [1] 335751 0
To assess the effect of oral AT-5214 or placebo 4 mg BID for 12 weeks on the investigator global assessment scale (IGA) in participants with moderate to severe facial acne vulgaris.

Investigator global assessment of acne severity will be conducted at Screening (required for entry into the study), Day 1, Week 4, Week 8, and Week 12 post-baseline. An IGA score will be established for each participant.
Timepoint [1] 335751 0
Absolute change from baseline in mean IGA score in each treatment group at Week 12 post-baseline (end of treatment).
The IGA score will be assessed at day 1, week 4, week 8 and week 12 post-baseline.
Secondary outcome [1] 425448 0
To assess the effect of oral AT-5214 or placebo 4 mg BID for 12 weeks on the acne lesion assessment which includes inflammatory, non-inflammatory, and total lesion counts in participants with moderate to severe facial acne vulgaris.

The acne lesion assessment is measured by the total lesion count which will be conducted at screening (required for entry into the study), Day 1, Week 4, Week 8, and Week 12 post-baseline (end of treatment). Total lesion count will be based on the investigator assessment. Assessment of lesion count (including both inflammatory and non-inflammatory lesions) will be conducted for each of the following six areas - forehead, both cheeks, nose, upper lip, chin. The total lesion count, defined as the sum of the total number of inflammatory and non-inflammatory lesions, will be derived for each of the areas and overall. The total number of inflammatory lesions will be derived as the sum of the inflammatory lesions reported across the six areas and the total number of non-inflammatory lesions will be derived as the sum of the non-inflammatory lesions reported across the six areas. Whenever possible, the same investigator who performs lesion counts for a subject at baseline should continue to perform lesion counts for that participant during the course of the study.
Timepoint [1] 425448 0
Absolute change from baseline in total lesion count including inflammatory and non-inflammatory, lesions in each treatment group at Week 8 and Week 12 post-baseline.

Percent change from baseline in lesion counts (inflammatory, non-inflammatory, and total lesion counts) in each treatment group at Week 8 and Week 12 post-baseline.
Secondary outcome [2] 425449 0
To assess the safety of oral AT-5214 4 mg BID for 12 weeks in participants with moderate to severe facial acne vulgaris.
Safety will be measured by routine clinical and laboratory procedures including blood samples to assess hematology, liver function, renal function and blood chemistry; urinalysis; physical examination; collection of vital signs including measurement of blood pressure measured using an automated sphygmomanometer, heart rate and respiratory rate measured using an automated device, and temperature using a tympanic thermometer; Electrocardiogram (ECG) and recording treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) in accordance with the Common Terminology Criteria for Adverse Events (CTCAE 5.0). AT-5214 has been administered to approximately 3000 patients for various conditions throughout the clinical development program, the vast majority of adverse events were mild and included dry mouth, constipation, blurred vision or dizziness.
Timepoint [2] 425449 0
Following enrolment into the study and administration of the first dose of study drug participants will undergo vital signs measurements comprising temperature, heart rate, respiratory rate and blood pressure during screening and on day 1 and Week 4, Week 8 and Week 12 post-baseline (End of treatment). A complete physical examination will occur during screening and Week 12, End of Treatment (EOT), a focused physical examination will be performed on day 1, Week 4 and Week 8 if clinically required. Clinical laboratory tests including chemistry, hematology and urinalysis will be collected during screening and day 1, Week 4, Week 8 and Week 12 (EOT), Triplicate 12-lead ECG recordings will be obtained during screening, day 1 and Week 12 (EOT). All AE and SAE information will be collected from signing of the informed consent until the follow up phone call, 10 days after EOT.
Secondary outcome [3] 434784 0
To assess the effect of oral AT-5214 or placebo 4mg BID for 12 weeks on the subject global assessment of response to treatment in participants with moderate to severe facial acne vulgaris.

Participants will assess their overall response to treatment using a study specific five-point reporting scale at weeks 4, 8 and 12 post baseline.
Timepoint [3] 434784 0
Count and percentage of participants in each treatment group feeling “much better” or “very much better or cleared” (score of 3 or 4) using a five-point scale (0=worse to 4=very much better) at Week 4, Week 8, and Week 12 post-baseline.
Secondary outcome [4] 434785 0
To assess the effect of oral AT-5214 or placebo 4mg BID for 12 weeks on the Dermatology Quality of Life Index (DLQI) in participants with moderate to severe facial acne vulgaris.
Participants will complete a DLQI which consists of 10 questions concerning participants' perception of the impact of skin diseases on different aspects of their health-related quality of life over the last week at baseline (day 1) and week 12 (EOT).
Timepoint [4] 434785 0
The change from baseline in DLQI at week 12 post-baseline.
Secondary outcome [5] 434786 0
To assess the effect of oral AT-5214 or placebo 4mg BID for 12 weeks on sebum production in participants with moderate to severe facial acne vulgaris.
Sebum production (sebometry) will be measured using a Sebumeter SBM815 and will include measurements on the forehead at screening, Day 1, Week 4, Week 8 and Week 12 post-baseline. Whenever possible, the same investigator who performs sebometry for a participant at baseline should continue to perform sebometry for that subject during the course of the study.
Timepoint [5] 434786 0
Absolute change from baseline in sebum production at Week 8 and Week 12 post-baseline in each treatment group

Eligibility
Key inclusion criteria
- Males and females aged >/= 16years at time of signing informed consent.
- Subject has oily skin as measured on three locations on the face using Sebometer, oily skin being defined as sebum level >100mcg/cm2.
- Subject has moderate to severe (3 or 4 on IGA scale) facial acne vulgaris (including the nose).
- Nonsmoker and/or ex-smoker who has discontinued smoking and/or use of nicotine-containing products, including vaping, for at least 6 months prior to Screening.
- Subject has used the same type and brand of make-up, other facial products (including cleanser) and hair products (e.g., shampoo, gel, hair spray, mousse, etc.) for at least one month prior to the study start and agrees to continue his/her other general skin and hair care products and regimen for the entire study.
- Body mass index (BMI) within the range 18 to 30 kg/m2 (inclusive).
- Females of childbearing potential and not abstinent, must be willing to use at least 2 highly effective methods of contraception (hormonal contraception [stable dose for 3 months], intrauterine device/intrauterine hormone-releasing system, and barrier contraceptive method [diaphragm, cervical cap, contraceptive sponge, condom) from screening to 30 days after the last dose of study intervention. Females who are abstinent are not required to use a contraceptive method unless they become sexually active. Alternatively, females must be postmenopausal for >/=1 year or surgically sterile (with tubal ligation, hysterectomy, or bilateral oophorectomy) for >/=6 months.
- Males with female partners of childbearing potential will agree to use barrier contraceptive (i.e., condom) and their female partners must use a highly effective method of contraception from screening to 90 days after the last dose of study intervention. Males also must refrain from sperm donations during this time period. Males who are abstinent are not required to use a contraceptive method unless they become sexually active.
Minimum age
16 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Subject has rosacea.
- Presence of a significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinological, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data.
- Abnormal blood pressure (resting heart rate < /=40 or >/=100 bpm or resting blood pressure <90/40 mmHg or >150/90 mmHg) at screening or before the first administration of study intervention.
- Any other abnormal vital signs that are considered to be clinically significant by the investigator.
- Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
- Breast cancer within the past 10 years.
- Any clinically significant laboratory abnormality at the screening visit or before the administration of the first dose of study intervention.
- Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- QTcF (QT with Fredericia’s correction) >/=450 msec.
- Subject is pregnant, lactating, or is planning to become pregnant during the study.
- Inability to tolerate oral medication.
- Subject has used any of the following topical preparations on the face:
- Topical anti-acne treatments including but not limited to over-the-counter acne cleaners or treatments, benzoyl peroxide, azelaic acid, sulfa-based products, corticosteroids and salicylic acid within 2 weeks of the initiation of treatment.
- Retinoids, including tazarotene, adapalene, tretinoin, within 4 weeks of the initiation of treatment.
- Topical anti-acne treatments containing antibiotics within 4 weeks of the initiation of treatment.
Subject has used any of the following systemic medications:
- Corticosteroids (including intramuscular and intralesional injections) within four weeks of the initiation of treatment. Inhaled, intranasal or ocular corticosteroids are allowed if use is stable (stable use is defined as dose and frequency unchanged for at least four [4] weeks prior to the initiation of treatment).
- Antibiotics within 4 weeks of the initiation of treatment with the exception of 5 days or less of antibiotic therapy during this period, but with no antibiotics use permitted within 1 week prior to the initiation of treatment.
- Spironolactone within 4 weeks of the initiation of treatment with the exception of 5 days or less of spironolactone therapy during this period, but with no spironolactone use permitted within 1 week prior to the initiation of treatment.
- Retinoid therapy within 6 months of the initiation of treatment.
- Live vaccine(s) within 1 month before Screening or plans to receive such vaccines during the study.
- Currently enrolled in an investigational drug or device study. Received an investigational drug or treated with an investigational device within 60 days or a minimum of 5 half-lives of the active investigational product prior to screening.
- Positive prestudy drug screen.
- Positive human immunodeficiency virus (HIV) or hepatitis C antibody test (HCV), or hepatitis B surface antigen (HBsAg) at screening or 3 months before enrollment.
- Subject is a smoker or user of nicotine products. Ex-smokers are eligible as long as they stopped smoking at least 6 months prior to Screening.
- Subject has the need or plans to be exposed to artificial tanning devices or excessive sunlight during the trial.
- Facial procedures, including light treatment, lasers, peels and dermabrasion within 2 months prior to initiation of treatment and throughout the study.
- Regular alcohol consumption within 6 months before the study defined, current evidence of substance dependence or self-reported alcoholic intake > 2 drinks/day for female subjects and > 3 drinks/day for male subjects.
- Regular use of known drugs of abuse or a history of drug abuse within 12 months prior to screening.
- Sensitivity to any of the study drug, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.

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)
A computerized randomization list will be created by an unblinded statistician or designee. Subjects will be randomized to receive either AT-5214 or placebo.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A computerized randomization list will be used.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The sample size for this study is approximately 100 subjects, to allow for assessment of the study outcomes.

The following analysis sets are defined:
The All Enrolled Analysis Set will consist of all subjects who provided informed consent.

The Intent-to-treat (ITT) Analysis Set will consist of all randomized subjects. Subjects will be analyzed according to the treatment they were randomized to if this differs from that which they actually received. All baseline characteristics analyses will be based on the ITT Analysis Set.

The Safety Analysis Set will consist of all subjects who receive any amount of study drug (AT-5214 or placebo). Subjects will be analyzed according to the treatment they actually received, if this differs from that to which the subject was randomized. All safety analyses will be based on the Safety Analysis Set.

The modified Intent-to-treat (mITT) Analysis Set will consist of all subjects in the ITT Analysis Set who have baseline and post-baseline data for at least one of the efficacy assessments. Subjects will be analyzed according to the treatment they were randomized to if this differs from that which they actually received. All efficacy analyses will be based on the mITT Analysis Set.

The Per Protocol (PP) Analysis Set will consist of all subjects in the mITT set who were at least 80% compliant with study drug and who had no major protocol violations. Subjects will be analyzed according to the treatment they actually received, if this differs from that to which the subject was randomized. Supportive efficacy analyses will be based on the PP Analysis Set.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/08/2024
Actual
Date of last participant enrolment
Anticipated
1/04/2025
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
100
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 25376 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [2] 26871 0
St George Dermatology & Skin Cancer Centre - Kogarah
Recruitment postcode(s) [1] 41106 0
3065 - Fitzroy
Recruitment postcode(s) [2] 42934 0
2217 - Kogarah

Funding & Sponsors
Funding source category [1] 314566 0
Commercial sector/Industry
Name [1] 314566 0
Atacama Therapeutics Australia, Pty Ltd.
Country [1] 314566 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Atacama Therapeutics Australia, Pty Ltd.
Address
HWT Tower Level 17, 40 City Road, Southbank, VIC 3006,AUSTRALIA
Country
Australia
Secondary sponsor category [1] 316527 0
Commercial sector/Industry
Name [1] 316527 0
InClin Pty Ltd
Address [1] 316527 0
Suite 210/25-29 Berry StreetNorth Sydney, NSWAustralia, 2060
Country [1] 316527 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313602 0
St Vincent's Hospital Melbourne Human Research Ethics Committee
Ethics committee address [1] 313602 0
Ethics committee country [1] 313602 0
Australia
Date submitted for ethics approval [1] 313602 0
22/08/2023
Approval date [1] 313602 0
10/10/2023
Ethics approval number [1] 313602 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 128714 0
Dr Ben Daniels
Address 128714 0
St Vincent's Hospital Melbourne, Dermatology Department, 41 Victoria Parade, Fitzroy, VIC, Australia 3065
Country 128714 0
Australia
Phone 128714 0
+61 411 536 668
Fax 128714 0
Email 128714 0
[email protected]
Contact person for public queries
Name 128715 0
Taylor Kilfoil
Address 128715 0
InClin Inc, Suite 210 / 25-29 Berry Street, North Sydney, NSW, Australia, 2060
Country 128715 0
Australia
Phone 128715 0
+61 408 880 403
Fax 128715 0
Email 128715 0
[email protected]
Contact person for scientific queries
Name 128716 0
Taylor Kilfoil
Address 128716 0
InClin Inc, Suite 210 / 25-29 Berry Street, North Sydney, NSW, Australia, 2060
Country 128716 0
Australia
Phone 128716 0
+61 408 880 403
Fax 128716 0
Email 128716 0
[email protected]

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


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.