To Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Oral AL01211 in Healthy Volunteers and Autosomal Dominant Polycystic Kidney Disease Subjects

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Brief Title

To Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Oral AL01211 in Healthy Volunteers and Autosomal Dominant Polycystic Kidney Disease Subjects

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 and autosomal dominant polycystic
      kidney disease subjects
    

Detailed Description

      This study is a Phase 1, first in human (FIH), randomized, double-blind, placebo-controlled
      study of AL01211 in healthy adult participants and adult patients with autosomal dominant
      polycystic kidney disease.

      The study consists of three 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.

      Part C will investigate the safety and tolerability, pharmacokinetics and pharmacodynamics of
      AL01211 in a multiple dose study in 18 adult patients with a confirmed diagnosis of autosomal
      dominant polycystic kidney disease.
    

Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

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

Secondary Outcome

 To assess the pharmacokinetics of AL01211 in healthy adult participants/ADPKD patients

Condition

Autosomal Dominant Polycystic Kidney

Intervention

AL01211 or Placebo (Part A)

Study Arms / Comparison Groups

 Part A Healthy volunteers: Single ascending doses
Description:  

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

98

Start Date

June 8, 2021

Completion Date

June 30, 2022

Primary Completion Date

June 1, 2022

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.

        For Part C (ADPKD)

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

          1. Between 18 and 55 years of age, inclusive at the time of informed consent.

          2. Evidence of diagnosis of ADPKD by modified Pei-Ravine criteria:

               -  At least 3 cysts per kidney by sonography or at least 5 cysts by CT or MRI with
                  family history of ADPKD or

               -  At least 10 cysts per kidney by any radiologic method and exclusion of other
                  cystic kidney diseases if without family history.

          3. Must sign an iCF indicating that they understand the purpose of, and procedures
             required for the study and are willing to participate in the study.

          4. Estimated glomerular filtration rate (eGFR) ≥ 30.0 mL/min/1.73 m2 and ≤ 89.0
             mL/min/1.73 m2.

          5. BMI between 20.0 and 34.9 kg/m2.

          6. 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.

          7. Participants must have no relevant dietary restrictions,

          8. 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 (OCPs, long-acting implantable hormones, and
                  injectable hormones)

               -  A vaginal ring or an 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 postvasectomy 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 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 are exclusively 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 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.

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

        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.

        For Part C (ADPKD): Exclusion criteria for Parts A and B plus

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

          1. Proteinuria > 500 mg/day.

          2. Unstable cerebral aneurysm.

          3. Prior use of tolvaptan or lixivaptan within the past 3 months.

          4. Prior use of somatostatin analogs (e.g., lanreotide, pasireotide, octreotide, etc.),
             metformin, nicotinamide, bardoxolone, venglustat, demeclocyline, or mammalian target
             of rapamycin (mTOR) kinase inhibitors (e.g., everolimus, sirolimus, etc.) to treat
             ADPKD within the past 6 months.
      

Gender

All

Ages

18 Years - 55 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Ben Snyder, MBBS, FRACP, 415-342-3215, [email protected]

Location Countries

Australia

Location Countries

Australia

Administrative Informations


NCT ID

NCT04908462

Organization ID

AL01211-101


Responsible Party

Sponsor

Study Sponsor

AceLink Therapeutics, Inc.

Collaborators

 Novotech (Australia) Pty Limited

Study Sponsor

Ben Snyder, MBBS, FRACP, Principal Investigator, Nucleus Network Pty Ltd


Verification Date

July 2021