Status:

TERMINATED

A Single Ascending and Repeated Dose Study of Oral ZF874 in Healthy Volunteers and PiXZ Subjects

Lead Sponsor:

Z Factor Limited

Collaborating Sponsors:

Hammersmith Medicines Research

Centessa Pharmaceuticals plc

Conditions:

Alpha1 Anti-Trypsin Deficiency

Eligibility:

All Genders

18-72 years

Phase:

PHASE1

Brief Summary

This study is composed of two parts. Part A: will test single doses of ZF874 in a double-blind, randomised, placebo-controlled and dose-escalating design (except Group 7, which will be open-label and ...

Detailed Description

Part A: Enrolment of up to 54 healthy men and women is planned, in up to 7 groups. Each of the first 6 groups will consist of 8 subjects and the 7th group will consist of 6 subjects. Subjects will rec...

Eligibility Criteria

Inclusion

  • Part A: healthy Caucasian males or females, aged 18-65 years at the time of consent; Part B: males or females of general good health, aged 18-72 years at the time of consent.
  • Body mass index of 18.0-30.0 kg/m\^2 (Part A) and 18.0-35.0 kg/m\^2 (Part B).
  • Able to understand the nature of the trial and any hazards of participating in it. Able to communicate satisfactorily with the investigator and to participate in, and comply with the requirements of the entire trial
  • Willing to give written fully informed consent to participate
  • Agree to follow the contraception requirements of the trial
  • Agree not to donate blood or blood products during the study and for up to 3 months after the trial medication
  • Registered with a General Practitioner in the United Kingdom
  • Willing to give written consent to have data entered into The Over-volunteering Prevention System \[Part B only\]
  • Confirmed genotype with at least one Z alpha-1-antitrypsin allele (PiXZ)

Exclusion

  • Woman who is pregnant or lactating, or woman of child-bearing potential who is sexually active and not using a highly effective method of contraception
  • Clinically relevant abnormal history, physical findings, ECG, or laboratory values at the pre-trial screening assessment that could interfere with the objectives of the trial or the safety of the volunteer
  • Acute or chronic illness or history of chronic illness sufficient to invalidate the volunteer's participation in the trial or make it unnecessarily hazardous
  • Impaired endocrine, thyroid, hepatic, respiratory or renal function, diabetes mellitus, coronary heart disease, or history of any psychotic mental illness
  • Creatinine clearance \<60 mL/min/1.73m2
  • Active cancer or to be actively on cancer therapy, or diagnosis of cancer (except for Basal Cell Carcinoma, Squamous Cell Carcinoma (fully excised), or Cervical Intra-epithelial Neoplasia in situ) in the 5 years before the first dose of trial medication.
  • Surgery (eg stomach bypass) or medical condition that might affect absorption of medicines
  • Presence or history of severe adverse reaction to any relevant drug
  • During the 28 days before the first dose of trial medication, the use of prescription medicine judged by the investigator to have the potential to influence the results of the study; or during the 7 days before the first dose of trial medication, the use of a herbal supplement or an over-the-counter medicine, with the exception of ibuprofen
  • Receipt of a COVID-19 vaccine within 14 days before the first dose of trial medication; exhibition of symptoms suspected to be related to COVID-19 within 28 days before the first dose of trial medication; or receipt of a positive COVID-19 test during the 28 days before the first dose of trial medication
  • Receipt of an investigational product (including prescription medicines) as part of another clinical trial within 3 months before admission to this study; in the follow-up period of another clinical trial at the time of screening for this study
  • Recent drug or alcohol abuse (within 2 years before screening), or intake of more than 3 units of alcohol daily (for men) or 2 units of alcohol daily (for women); or use of cigarettes or nicotine-containing products during 30 days before the first dose of trial medication until the end of the study
  • Blood pressure and heart rate in supine position at the screening examination outside the ranges: blood pressure 90-160 mm Hg systolic, 40-90 mm Hg diastolic; heart rate 40-100 beats/min
  • Possibility that the volunteer will not cooperate with the requirements of the protocol
  • Evidence of drug abuse on urine testing
  • Positive test for hepatitis B virus, hepatitis C virus or human immunodeficiency virus
  • Loss of more than 400 mL blood during 3 months before the trial, eg as a blood donor
  • Objection by General Practitioner to volunteer entering trial
  • Part A, Cohort 7 only:
  • \- Vegans, vegetarians, or unwilling to eat a high-fat breakfast containing bacon.
  • Part B only:
  • \- Undergone liver transplantation

Key Trial Info

Start Date :

August 3 2020

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

September 12 2022

Estimated Enrollment :

69 Patients enrolled

Trial Details

Trial ID

NCT04443192

Start Date

August 3 2020

End Date

September 12 2022

Last Update

September 19 2022

Active Locations (5)

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Page 1 of 2 (5 locations)

1

MAC Clinical Research Manchester

Manchester, Greater Manchester, United Kingdom, M13 9NQ

2

MAC Clinical Research, Barnsley

Barnsley, United Kingdom, S75 3DL

3

MAC Clinical Research, Leeds

Leeds, United Kingdom, LS10 1DU

4

Hammersmith Medicines Research

London, United Kingdom, NW10 7EW