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

NCT04443192 · Status: TERMINATED · Phase: PHASE1 · Type: INTERVENTIONAL · Enrollment: 69

Last updated 2022-09-19

No results posted yet for this study

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 without placebo). Up to 7 groups of 6-8 healthy volunteers will receive an oral dose of ZF874 or matching placebo (6 active: 2 placebo in Groups 1-6; 6 active in Group 7). The dosing of the first 2 subjects (1 active and 1 placebo) will take place before dosing of the remainder of the group in Groups 1-6, with morning doses given in the fasted state. The dose will be escalated only if the safety and tolerability of the previous highest dose are acceptable, and the plasma concentrations of ZF874 are predicted to remain below the toxicokinetic exposure limit, as determined by the Safety Review Group. Group 7 will consist of 6 subjects, all of whom will receive ZF874 after consuming a standard high-fat breakfast. Dosing of the first 2 subjects before the rest of the group is not required in Group 7, as 6 subjects have already safely received ZF874 at this dose in Group 3 and 12 subjects have already safely received higher doses in Groups 4 and 5.

The dose selected for Part A, Group 7 was chosen as the dose has previously been given to subjects fasted in Group 3, and it was safe and well tolerated, allowing for comparison for the food effect, and higher doses have been tested in Part A with no safety concerns.

Part B: Multiple Ascending Doses in subjects carrying at least one Z mutated alpha-1-antitrypsin (Z-A1AT) allele (PiXZ subjects): Up to 4 groups of up to 5 PiXZ subjects will be enrolled in Part B (Groups 1-4). In Group 1, up to 4 subjects will receive twice daily doses of either ZF874 or placebo on 28 consecutive days. The dose level (dose and dose regimen) selected for Part B Group 1 will be based on review of the available results from Part A. In Groups 2-4, up to 5 PiXZ subjects will receive ZF874 twice daily by mouth for 28 days; no subjects will receive placebo. The dose for Groups 2 - 4 will not exceed the doses already given in Part A.

Conditions

  • Alpha1 Anti-Trypsin Deficiency

Interventions

DRUG

ZF874

ZF874 is a novel chemical chaperone that is specifically designed to rescue the folding of the Z variant of alpha-1-antitrypsin (A1AT). It is being developed for the treatment of alpha-1-antitrypsin deficiency (AATD) caused by the Z-mutation.

DRUG

Placebo

Placebo to ZF874

Sponsors & Collaborators

  • Hammersmith Medicines Research

    collaborator OTHER

  • Centessa Pharmaceuticals plc

    collaborator INDUSTRY

  • Z Factor Limited

    lead INDUSTRY

Principal Investigators

  • Malcolm Boyce, BSc MD FRCP FFPM · HMR

  • Giuseppe Fiore, MSc MD · MAC Clinical Research

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Max Age
72 Years
Sex
ALL
Healthy Volunteers
Yes

Timeline & Regulatory

Start
2020-08-03
Primary Completion
2022-09-12
Completion
2022-09-12

Countries

  • United Kingdom

Study Locations

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Entities

Drugs

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT04443192 on ClinicalTrials.gov