To Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Oral AL01211 in Healthy Volunteers

• ClinicalTrials.gov Identifier: NCT04908462
• Recruitment Status: Completed
• First Posted: June 1, 2021
• Last Update Posted: October 14, 2022
• Sponsor: AceLink Therapeutics, Inc.
• Collaborator: Novotech (Australia) Pty Limited
• Information provided by (Responsible Party): AceLink Therapeutics, Inc.

Tracking Information

• First Submitted Date: May 18, 2021
• First Posted Date: June 1, 2021
• Last Update Posted Date: October 14, 2022
• Actual Study Start Date: June 8, 2021
• Actual Primary Completion Date: June 20, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 16, 2022)

To assess the safety and tolerability measures of AL01211 through Adverse Events/Serious Adverse Events in healthy adult participants [ Time Frame: Baseline to End of the Treatment assessed up to an average of 90 days ]

Number of participants with treatment related adverse events as assessed through CTCAE v5.0

Original Primary Outcome Measures (submitted: May 28, 2021)

To assess the safety and tolerability measures of AL01211 through Adverse Events/Serious Adverse Events in healthy adult participants/ADPKD patients. [ Time Frame: Baseline to End of the Treatment assessed up to an average of 90 days ]

Number of participants with treatment related adverse events as assessed through CTCAE v5.0

Current Secondary Outcome Measures (submitted: May 16, 2022)

• To assess the pharmacokinetics of AL01211 in healthy adult participants [ Time Frame: Baseline to End of the Treatment assessed up to an average of 56 days ]
  The following parameters are used for pharmacokinetics: AUC0-last, AUC0-24h
• Measurement of glucosylceramide in plasma and urine following oral dosing of AL01211 [ Time Frame: Baseline to End of the Treatment assessed up to an average of 56 days ]
  Change in glucosylceramide levels
• Measurement of monosialodihexosylganglioside in plasma and urine following oral dosing of AL01211 [ Time Frame: Baseline to End of the Treatment assessed up to an average of 56 days ]
  Change in monosialodihexosylganglioside levels

Original Secondary Outcome Measures (submitted: May 28, 2021)

• To assess the pharmacokinetics of AL01211 in healthy adult participants/ADPKD patients [ Time Frame: Baseline to End of the Treatment assessed up to an average of 56 days ]
  The following parameters are used for pharmacokinetics: AUC0-last, AUC0-24h
• Measurement of glucosylceramide in plasma and urine following oral dosing of AL01211 [ Time Frame: Baseline to End of the Treatment assessed up to an average of 56 days ]
  Reduction in glucosylceramide levels
• Measurement of monosialodihexosylganglioside in plasma and urine following oral dosing of AL01211 [ Time Frame: Baseline to End of the Treatment assessed up to an average of 56 days ]
  Reduction in monosialodihexosylganglioside levels

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: To Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Oral AL01211 in Healthy Volunteers
• Official 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
• Brief Summary: The study is designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of Oral AL01211 in healthy volunteers

Detailed Description

This study is a Phase 1, first in human (FIH), randomized, double-blind, placebo-controlled study of AL01211 in healthy adult participants

The study consists of two parts:

Part A will investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of AL01211 in a single ascending dose escalation study in approximately 40 healthy adult participants.

Part B will investigate the safety and tolerability, pharmacokinetics, and pharmacodynamics of AL01211 in a multiple ascending dose escalation study in approximately 40 healthy adult volunteers.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Autosomal Dominant Polycystic Kidney

Intervention

• Drug: AL01211 or Placebo (Part A)
  Five dose groups with doses ranging from 2mg to 60 mg
• Drug: AL01211 or Placebo (Part B)
  Five dose groups with doses ranging from 2-60 mg daily. Each separate dose given for 14 days

Study Arms

• Experimental: Part A Healthy volunteers: Single ascending doses
  Intervention: Drug: AL01211 or Placebo (Part A)
• Experimental: Part B Healthy Volunteers Multiple ascending doses
  Intervention: Drug: AL01211 or Placebo (Part B)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 12, 2022): 69
• Original Estimated Enrollment (submitted: May 28, 2021): 98
• Actual Study Completion Date: June 20, 2022
• Actual Primary Completion Date: June 20, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia

Administrative Information

• NCT Number: NCT04908462
• Other Study ID Numbers: AL01211-101
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: AceLink Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: AceLink Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Novotech (Australia) Pty Limited

Investigators

• Principal Investigator: Philip Ryan, MBBS, FRACP; Nucleus Network Pty Ltd.

• PRS Account: AceLink Therapeutics, Inc.
• Verification Date: October 2022