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

NCT04908462 | Completed Phase 1 DMC

• 1 other identifier: AL01211-101
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

Brief Summary

The study is designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of Oral AL01211 in healthy volunteers

Conditions

Autosomal Dominant Polycystic Kidney

Outcome Measures

Primary Outcomes (1)

• To assess the safety and tolerability measures of AL01211 through Adverse Events/Serious Adverse Events in healthy adult participants

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

  Baseline to End of the Treatment assessed up to an average of 90 days

Secondary Outcomes (3)

• To assess the pharmacokinetics of AL01211 in healthy adult participants

  Baseline to End of the Treatment assessed up to an average of 56 days

• Measurement of glucosylceramide in plasma and urine following oral dosing of AL01211

  Baseline to End of the Treatment assessed up to an average of 56 days

• Measurement of monosialodihexosylganglioside in plasma and urine following oral dosing of AL01211

  Baseline to End of the Treatment assessed up to an average of 56 days

Study Arms (2)

Part A Healthy volunteers: Single ascending doses

EXPERIMENTAL

Drug: AL01211 or Placebo (Part A)

Part B Healthy Volunteers Multiple ascending doses

EXPERIMENTAL

Drug: AL01211 or Placebo (Part B)

Interventions

AL01211 or Placebo (Part A) DRUG

Five dose groups with doses ranging from 2mg to 60 mg

Part A Healthy volunteers: Single ascending doses

AL01211 or Placebo (Part B) DRUG

Five dose groups with doses ranging from 2-60 mg daily. Each separate dose given for 14 days

Part B Healthy Volunteers Multiple ascending doses

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• For Part A (SAD) and Part B (MAD)
• Healthy male or female volunteers, between 18 and 55 years of age
• Participants in good health as determined by medical history, physical examination, vital signs, ECG, and clinical laboratory tests.
• Body Mass Index (BMI) between 20.0 and 34.9 kg/m2 (inclusive).
• 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.
• Participants must have no relevant dietary restrictions,
• 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.

You may not qualify if:

• For Part A (SAD) and Part B (MAD)
• Any concomitant disease, condition, or treatment that could interfere with the conduct of the study,.
• History or symptoms of significant psychiatric disease,
• 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).
• 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.
• Known hypersensitivity or allergy to AL01211 or excipient contained in the drug formulation.
• Uncontrolled hypertension of \> 140/90 mm Hg despite optimal therapy.
• 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
• 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).
• Impaired renal function as determined by the Investigator, based on an estimated glomerular filtration rate (eGFR) \< 90mL/min/1.73 m2 at Screening.
• 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).

Sponsors & Collaborators

• AceLink Therapeutics, Inc.: lead
• Novotech (Australia) Pty Limited: collaborator

Study Sites (1)

Nucleus Network

Melbourne, Victoria, 3004, Australia

Location

MeSH Terms

Conditions

Polycystic Kidney, Autosomal Dominant

Condition Hierarchy (Ancestors)

Polycystic Kidney Diseases; Kidney Diseases, Cystic; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Ciliopathies; Genetic Diseases, Inborn

Study Officials

• Philip Ryan, MBBS, FRACP

  Nucleus Network Pty Ltd.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2021
• First Posted: June 1, 2021
• Study Start: June 8, 2021
• Primary Completion: June 20, 2022
• Study Completion: June 20, 2022
• Last Updated: October 14, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)