WithdrawnPhase 1ACTRN12625000488404

A Phase 1 Randomized, Double-blind, Placebo-controlled Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MZE782 in Healthy Adults

Sponsor

Maze Therapeutics

Enrollment

24 participants

Start Date

Jul 1, 2025

Study Type

Interventional

Conditions

Chronic Kidney Disease Phenylketonuria

Summary

This Phase 1, randomised, placebo-controlled, double-blind clinical trial will assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of MZE782 when administered at increasing dose levels in healthy adult participants in Australia. Participants will receive MZE782 or matching placebo as multiple doses.

Eligibility

Sex: Both males and femalesMin Age: 18 YearssMax Age: 60 Yearss

Inclusion Criteria15

Age is 18 to 60 years (inclusive) at the time of signing the informed consent.
BMI is within 18.5 to 32.0 kg/m2 (inclusive) and weight is at least 55 kg.
Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
Overtly healthy, as determined by the investigator through medical history, physical examination, vital signs, ECGs, and laboratory safety tests performed at the screening visit and prior to administration of initial dose of study drug. Slight excursions outside the limits of normal may be acceptable if deemed to be clinically not significant by the investigator.
Negative tests for, HBsAg, anti-HCV, and HIV antibody at the screening visit (positive anti-HCV antibody allowed if HCV PCR is negative).
Biological female participants must have a negative pregnancy test at screening and at check-in. Not required of post-menopausal female participants if greater than or equal to 12 months without menses and follicle-stimulating hormone (FSH) documented in post-menopausal range (greater than or equal to 40 IU/L).
Use of highly effective contraception is required as follows:
i. Female participants of childbearing potential (ie, ovulating, premenopausal, and not surgically sterile;) must use highly effective methods of birth control starting 2 weeks prior to admission to the CRU until 33 days after the last administration of study drug. Highly effective methods of birth control are defined as those with 99% or greater efficacy (Trussell, 2004). Hormonal contraceptives are not prohibited but cannot be considered highly effective pending additional drug interaction investigations. Acceptable methods of birth control include:
a. Complete abstinence from sexual intercourse if this is the participant’s usual and preferred lifestyle.
b. Dual method of contraception including: i) condom in conjunction with a intrauterine device (hormonal or nonhormonal); ii) condom and tubal ligation/ occlusion; or iii) condom and vasectomy (with documented azoospermia 90 days post procedure).
Participants must agree to abstain from egg donation through 33 days after administration of the last dose of study drug.
ii. All male participants with sexual partners of childbearing potential must use highly effective methods of birth control from time of dosing until 93 days after the last administration of study drug, specifically double barrier contraception or complete abstinence if this is part of the participants usual lifestyle. Acceptable methods of double barrier contraception are: i) condom and hormonal contraception in female partner with hormonal contraception started at least 30 days prior; ii) condom and IUD; iii) or condom and tubal ligation/occlusion or iv) condom and vasectomy with documented azoospermia at least 90 days post procedure. Participants must agree to abstain from sperm donation through 93 days after administration of the last dose of study drug. Female partners of male participants should use a dual method of contraception (as described for female participants) and includes hormonal contraception as long as it is part of the dual method.
Participants must agree to abstain from sperm donation through 93 days.
iii. Participants with solely same-sex partners are not required to use contraception.
Post-menopausal female participants or those with a history of hysterectomy or bilateral salpingectomy and/or bilateral oophorectomy do not require contraception if greater than or equal to 12 months without menses and follicle-stimulating hormone (FSH) documented at screening in post-menopausal range (greater than or equal to 40 IU/L).

Exclusion Criteria22

Any concurrent condition that, in the opinion of the investigator, would interfere with the evaluation of the investigational product or lead to increased risk of harm (s/p appendectomy is allowed).
Any chronic medical condition requiring ongoing treatment.
History of cancer within the past 3 years, except for treated non-melanoma skin cancer.
Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks prior to the screening visit, as per investigator judgement. Additionally, any major surgery (in the opinion of the investigator within 3 months prior to screening visit.
Clinically significant abnormal ECG, including but not limited to QTc >450 ms at screening and/or check-in or history of QT interval prolongation or known history of cardiac arrhythmia.
Note: ECGs may be repeated up to 3 times as per investigator discretion at any timepoint to obtain a clinically reliable result.
Vital sign outside the normal ranges, specifically for blood pressure and heart rate taken in seated or supine position, as well as for tympanic temperature:
i. Systolic blood pressure 140 mg Hg, inclusive
ii. Diastolic blood pressure 90 mg Hg, inclusive
iii. Heart rate 99 bpm, inclusive
iv. Body temperature (tympanic) outside of the range 35.5 - 37.5 °C
Note: assessments for vital signs may be repeated as per investigator discretion at any timepoint to obtain a clinically reliable result.
History of drug hypersensitivity (based on investigator judgement) or anaphylaxis.
Use of any investigational drug within 30 days or <5 half-lives, whichever is longer, prior to first dose of study drug.
Consumption of food and/or beverages containing caffeine- or xanthine-containing products (eg, coffee, tea, cola drinks, and chocolate), red wine or other alcohol, Seville oranges or Seville orange juice, grapefruit or grapefruit juice, or poppy seeds within 48 hours prior to check-in.
Known sensitivity to any of the study drug formulation components.
More than social/casual use of any tobacco or nicotine products (including e-cigarettes, vaping, or dipping) within the last 2 months before the screening visit (social/casual use is up to 2 cigarettes/day or up to 5-10/week) and any use of tobacco or nicotine products within 72 hours before the screening visit (less than 2 cigarettes/day or up to 5-10/week within the 2 months before screening is not exclusionary as long as there has been no use in the 72 hours prior to screening). Testing for cotinine will be performed at screening and check-in as per the SOA and must be negative for inclusion. Testing for cotinine may be repeated at the discretion of the investigator should the investigator suspect that a false-positive result has occurred.
History of alcohol or drug abuse within the past 12 months or positive drug screen (including marijuana) at the time of screening or check-in visit. Consumption of more than 14 drinks per week by males or more than 10 per week by females would be considered alcohol abuse.
Donation of any blood or blood products at a blood bank or donation center within the 30 days prior to the screening visit or after the end of study or receipt of blood or blood products within 3 months prior to screening visit.
Strenuous exercise within 48 hours of check-in visit.
Pregnant, breastfeeding, or planning to become pregnant (either self or partner).
In the investigator’s judgement, the participant should not participate.

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Interventions

This is a Phase 1, randomized, double-blinded, placebo-controlled, multiple dose escalation (MAD) study designed to assess the safety, tolerability, and pharmacokinetics (PK) of MZE782 in healthy adult volunteers. Up to three cohorts of 8 participants each (6 active and 2 placebo) will be enrolled. On Day 1, participants will be randomized to receive an oral administration of MZE782 or placebo tablets under fasted conditions. The proposed starting dose to be evaluated will be 720 mg MZE782 or placebo tablets daily for 7 days. Following review of safety and PK data by the Safety Review Committee (SRC) and determination of adequate safety and tolerability in Cohort 1, dose escalation will occur. The proposed dose for Cohort 2 is 960 mg MZE782 or placebo tablets daily for 7 days. The dose of Cohort 3 has not been determined. Participants will be discharged from the Clinical Research Unit (CRU) on Day 10, at approximately 72 hours after the last dose. Participants will be administered study drug in the CRU under the direct medical supervision of the investigator or designee.