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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04908462




Registration number
NCT04908462
Ethics application status
Date submitted
18/05/2021
Date registered
1/06/2021
Date last updated
14/10/2022

Titles & IDs
Public title
To Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Oral AL01211 in Healthy Volunteers
Scientific title
A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose in Healthy Volunteers and Autosomal Dominant Polycystic Kidney Disease Subjects Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Oral AL01211
Secondary ID [1] 0 0
AL01211-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Autosomal Dominant Polycystic Kidney 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Other renal and urogenital disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AL01211 or Placebo (Part A)
Treatment: Drugs - AL01211 or Placebo (Part B)

Experimental: Part A Healthy volunteers: Single ascending doses -

Experimental: Part B Healthy Volunteers Multiple ascending doses -


Treatment: Drugs: AL01211 or Placebo (Part A)
Five dose groups with doses ranging from 2mg to 60 mg

Treatment: Drugs: AL01211 or Placebo (Part B)
Five dose groups with doses ranging from 2-60 mg daily. Each separate dose given for 14 days
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
To assess the safety and tolerability measures of AL01211 through Adverse Events/Serious Adverse Events in healthy adult participants
Timepoint [1] 0 0
Baseline to End of the Treatment assessed up to an average of 90 days
Secondary outcome [1] 0 0
To assess the pharmacokinetics of AL01211 in healthy adult participants
Timepoint [1] 0 0
Baseline to End of the Treatment assessed up to an average of 56 days
Secondary outcome [2] 0 0
Measurement of glucosylceramide in plasma and urine following oral dosing of AL01211
Timepoint [2] 0 0
Baseline to End of the Treatment assessed up to an average of 56 days
Secondary outcome [3] 0 0
Measurement of monosialodihexosylganglioside in plasma and urine following oral dosing of AL01211
Timepoint [3] 0 0
Baseline to End of the Treatment assessed up to an average of 56 days

Eligibility
Key inclusion criteria
For Part A (SAD) and Part B (MAD)

To be eligible for the study, participants must meet all of the following inclusion
criteria:

1. Healthy male or female volunteers, between 18 and 55 years of age

2. Participants in good health as determined by medical history, physical examination,
vital signs, ECG, and clinical laboratory tests.

3. Body Mass Index (BMI) between 20.0 and 34.9 kg/m2 (inclusive).

4. Participants who smoke no more than 2 cigarettes per day or equivalent per week
(includes e-cigarettes) can be included in the study but must be willing to abstain
from smoking during confinement periods.

5. Participants must have no relevant dietary restrictions,

6. Females must be non-pregnant and non-lactating, and must use an acceptable, highly
effective double contraception from Screening until at least 30 days have passed since
study drug administration , including the follow-up period. Double contraception is
defined as a condom AND one other form of the following:

- Established hormonal contraception (oral contraceptive pills [OCPs], long-acting
implantable hormones, and injectable hormones) for at least 1 month prior to
Screening

- A vaginal ring or an intrauterine device [IUD]

- Documented evidence of surgical sterilization at least 6 months prior to
Screening (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, or
bilateral oophorectomy) for women or vasectomy at least 90 days prior to
Screening for men (with appropriate post-vasectomy documentation of the absence
of sperm in semen), provided the male partner is a sole partner.

- Women not of childbearing potential must be postmenopausal for = 12 months.
Postmenopausal status will be confirmed through testing of follicle-stimulating
hormone (FSH) levels = 40 IU/mL at Screening for amenorrhoeic female
participants. Females who are abstinent from heterosexual intercourse will also
be eligible.

Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods)
and withdrawal are not considered highly effective methods of birth control.
Participant complete abstinence for the duration of the study and for 1 month after
the last study treatment is acceptable.

Female participants who exclusively are in same sex relationships are not required to
use contraception.

- Males must be surgically sterile (> 90 days since vasectomy with no viable sperm),
abstinent, or if engaged in sexual relations with a woman of childbearing potential
(WOCBP), the participant and his partner must be surgically sterile (e.g., tubal
occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or using an
acceptable, highly effective contraceptive method from Screening until at least 90
days have passed since study drug administration, including the follow-up period.
Acceptable methods of contraception include the use of condoms and the use of an
effective contraceptive for the female partner that includes: OCPs, long-acting
implantable hormones, injectable hormones, a vaginal ring, or an IUD. Participants
with same sex partners (abstinence from penile-vaginal intercourse) are eligible when
this is their preferred and usual lifestyle.

WOCBP must have a negative pregnancy test at Screening and Day -1 and be willing to
have additional pregnancy tests as required throughout the study.

Males must not donate sperm for at least 90 days after the last dose of AL01211.

7. Participants must have the ability and willingness to attend the necessary visits to
the CRU.

8. Must sign an informed consent form (ICF) indicating that they understand the purpose
of, and procedures required for the study and are willing to participate in the study.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
For Part A (SAD) and Part B (MAD)

A participant who meets any of the following exclusion criteria must be excluded from the
study:

1. Any concomitant disease, condition, or treatment that could interfere with the conduct
of the study,.

2. History or symptoms of significant psychiatric disease,

3. History or evidence of significant hepatic or renal disease or impairment, including
clinically significant abnormalities in laboratory test results (including complete
blood count, chemistry panel including kidney panel and liver function tests, and
urinalysis).

4. Evidence of an active or suspected cancer or a history of malignancy for at least 5
years, except for: nonmelanoma skin cancer considered cured, curatively treated
localized prostate cancer, or other in situ cancer.

5. Known hypersensitivity or allergy to AL01211 or excipient contained in the drug
formulation.

6. Uncontrolled hypertension of > 140/90 mm Hg despite optimal therapy.

7. Any of the following abnormal ECG findings at Screening:

- PR interval > 210 ms or < 120 ms

- QRS interval > 120 ms

- QTcF interval > 450 ms

- ST segment elevation or depression considered to be clinically significant

8. Any hepatic laboratory abnormality > 1.5 times the upper limit of the normal range
(ULN), including alanine aminotransferase (ALT), aspartate aminotransferase (AST), or
alkaline phosphatase (ALP).

9. Impaired renal function as determined by the Investigator, based on an estimated
glomerular filtration rate (eGFR) < 90mL/min/1.73 m2 at Screening.

10. Pregnant or lactating at Screening or planning to become pregnant (self or partner) at
any time during the study, including up to 30 days after study drug administration
(for female participants) or up to 90 days after study drug administration (for female
partners of male participants).

11. Fever or symptomatic viral or bacterial infection at time of Screening. Testing for
SARS-CoV-2 infection will be performed in accordance with local guidelines (health
authorities, Institutional Review Boards/Independent Ethics Committees, and study
centre policies) and at the discretion of the Investigator, if required.

12. Participants who have received live vaccines or attenuated vaccines within 1 month
before dosing. Participants may receive vaccination for SARS-CoV-2 at the discretion
of the Investigator as soon as they are eligible, and a vaccine is available.

13. The participant has, according to World Health Organization (WHO) Grading, a cortical
cataract greater than one-quarter of the lens circumference (Grade cortical cataract-2
[COR-2]) or a posterior subcapsular cataract > 2mm (Grade posterior subcapsular
cataract-2 [PSC-2]). Participants with nuclear cataracts will not be excluded.

14. The participant is currently receiving, or has received within the past month,
potentially cataractogenic medications, including a chronic regimen (more frequently
than every 2 weeks) of any route of corticosteroids (limited to medium and
high-potency topical steroids; intranasal steroids are acceptable) or any medication
that may cause cataract (such as phenothiazines and miotics, amiodarone, allopurinol,
and phenytoin), according to the Prescribing Information.

15. Positive test for hepatitis C antibody (HCV), hepatitis B surface antigen (HBsAg), or
human immunodeficiency virus (HIV) antibody at Screening.

16. Participants with a positive toxicology screening panel (urine test including
qualitative identification of barbiturates, tetrahydrocannabinol (THC), amphetamines,
benzodiazepines, opiates and cocaine), or alcohol breath test.

17. Participants with a history of substance abuse or dependency or history of
recreational intravenous (IV) drug use over the last 5 years (by self-declaration)

18. Regular alcohol consumption defined as >21 alcohol units per week (where 1 unit =
284mL of beer, 25mL of 40% spirit, or a 125mL glass of wine). Participant is unwilling
to abstain from alcohol beginning 48 hours prior to admission to the CRU until
completion of the primary Follow-up visit. (Part A [except Cohort A3]: Day 7; Part A
[Cohort A3]: Day 35; Part B: Day 21).

19. Use of any IP or investigational medical device within 30 days prior to Screening, or
5 half-lives of the product (whichever is the longest) or participation in more than
four investigational drug studies within 1 year prior to screening.

20. Use of any prescription medications (other than hormonal contraception: OCPs,
long-acting implantable hormones, injectable hormones, a vaginal ring or an IUD), over
the-counter (OTC) medication, herbal remedies, supplements or vitamins 2 weeks prior
to dosing and during the course of the study without prior approval of the
Investigator and MM. Simple analgesia (paracetamol, nonsteroidal anti-inflammatory
drug [NSAID]) may be permitted at the discretion of the Investigator.

21. History of anaphylaxis or other severe allergy to any drug, food, toxin, or other
exposure.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
8/06/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
20/06/2022
Sample size
Target
Accrual to date
Final
69
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 0 0
3004 - Melbourne

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AceLink Therapeutics, Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Novotech (Australia) Pty Limited
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The study is designed to evaluate the safety, tolerability, pharmacokinetics and
pharmacodynamics of Oral AL01211 in healthy volunteers
Trial website
https://clinicaltrials.gov/ct2/show/NCT04908462
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Philip Ryan, MBBS, FRACP
Address 0 0
Nucleus Network Pty Ltd.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04908462