Alpha1 Anti-Trypsin DeficiencyPhase 1NCT04443192
A Single Ascending and Repeated Dose Study of Oral ZF874 in Healthy Volunteers and PiXZ Subjects
A Phase 1 study testing ZF874 in people with Alpha1 Anti-Trypsin Deficiency, run by Z Factor Limited at 5 sites in United Kingdom.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 72 yearsHealthy volunteers can take part
- Conditions the study is for
- Alpha1 Anti-Trypsin Deficiency
- What is being tested?
- ZF874
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 69 participants
- Where
- 5 sitesUnited Kingdom
- Study dates
- 3 Aug 2020to 12 Sep 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 72 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
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- 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)
Who cannot join
- 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.
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- 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
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United Kingdom5 sites
MAC Clinical Research, Barnsley
Barnsley, S75 3DL
MAC Clinical Research, Leeds
Leeds, LS10 1DU
Hammersmith Medicines Research
London, NW10 7EW
MAC Clinical Research Manchester
Manchester, Greater Manchester, M13 9NQ
MAC Clinical Research, Teesside
Stockton-on-Tees, TS17 6EW
About this study
Official title: A Double-blind, Randomised, Placebo-controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single Ascending and Repeated Doses of Orally Administered ZF874 in Healthy Volunteers and PiXZ Subjects
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.
Read the 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 receive either one or two oral dose(s) of either ZF874 or placebo, in the fasted state in the first 6 groups. There will be up to 7 dose levels of ZF874. In each of the first 6 groups, two subjects (one placebo, one ZF874) are to be dosed in a double-blind manner at least 23 hours prior to the remainder of the group. In the absence of any safety concerns in the leading subjects, the remaining subjects will be dosed, at intervals of at least 10 minutes. 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 Cohort 3, and 12 subjects have already safely received higher doses in Cohorts 4 and 5. In Group 7, all subjects will receive a single dose of ZF874 by mouth, after consuming a high-fat breakfast. All subjects will be screened in the 28 days before their dose of trial medication. Subjects will be resident on ward from 1 day before their dose (Day -1) until 48 hours after dosing (Day 3). They will return for a follow-up visit 5-7 days after their dose (Day 6-8).
Part B: In Group 1, up to 4 subjects will receive twice daily doses of either ZF874 or placebo on 28 consecutive days (up to 3 active: up to 2 placebo). 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 doses will be selected after reviewing the available safety and pharmacokinetic results from previous groups, but will not exceed the doses already given in Part A.
Subjects will be pre-screened to confirm PiXZ genotype within 84 days before their dose of trial medication. Once their genotype is confirmed, they will be screened in the 28 days before their dose of study medication. Subjects will be resident on the ward from 1 day before their first dose (Day -1) until 1 hour after they receive their second dose (Day 2). They will then attend 6 outpatient visits before returning to the ward and be resident from Day 27 until 24 hours after the final dose (Day 29). They will return for further outpatient visits on Days 36, 43 and 50, and for a follow-up visit 28-30 days after their final dose (Day 56-58).
- Conditions
- Alpha1 Anti-Trypsin Deficiency
- Being tested
- ZF874, Placebo
- Medical subject headings
- alpha 1-Antitrypsin Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZF874Drug
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.
PlaceboDrug
Placebo to ZF874
| Study group | Role | What they receive |
|---|---|---|
| Part A Cohort 1 - ZF874 | Active comparator | Single oral dose of ZF874 by mouth in the fasted state. Dose Level 1 Receives: Drug: ZF874 |
| Part A - Placebo to ZF874 - Single Dose | Placebo comparator | Single oral dose of placebo by mouth in the fasted state Receives: Drug: Placebo |
| Part A Cohort 2 - ZF874 | Active comparator | Single oral dose of ZF874 by mouth in the fasted state. Dose Level 2 Receives: Drug: ZF874 |
| Part A Cohort 3 - ZF874 | Active comparator | Single oral dose of ZF874 by mouth in the fasted state. Dose Level 3 Receives: Drug: ZF874 |
| Part A Cohort 4 - ZF874 | Active comparator | Single oral dose of ZF874 by mouth in the fasted state. Dose Level 4 Receives: Drug: ZF874 |
| Part A - Placebo to ZF874 - Two Doses | Placebo comparator | Two doses of placebo (12 h apart) by mouth in the fasted state Receives: Drug: Placebo |
| Part A Cohort 5 - ZF874 - Two Doses | Active comparator | Two doses of ZF874 (12 h apart) by mouth in the fasted state. Dose Level 5 Receives: Drug: ZF874 |
| Part A Cohort 6 - ZF874 - Two Doses | Active comparator | Two doses of ZF874 (12 h apart) by mouth in the fasted state. Dose Level 6 Receives: Drug: ZF874 |
| Part A Cohort 7 - ZF874 - Single Dose | Active comparator | Single oral dose of ZF874 by mouth after consuming a high-fat breakfast. Dose Level 3 Receives: Drug: ZF874 |
| Part B Cohort 1 - ZF874 | Active comparator | Two doses of ZF874 (12 h apart) by mouth daily for 28 days. Receives: Drug: ZF874 |
| Part B Cohort 1 - Placebo to ZF874 | Placebo comparator | Two doses of placebo (12 h apart) by mouth daily for 28 days. Receives: Drug: Placebo |
| Part B Cohort 2 - ZF874 | Active comparator | Two doses of ZF874 (12 h apart) by mouth daily for 28 days. Receives: Drug: ZF874 |
| Part B Cohort 3 - ZF874 | Active comparator | Two doses of ZF874 (12 h apart) by mouth daily for 28 days. Receives: Drug: ZF874 |
| Part B Cohort 4 - ZF874 | Active comparator | Two doses of ZF874 (12 h apart) by mouth daily for 28 days. Receives: Drug: ZF874 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment
Safety and tolerability
Measured: Part A: Day 1 to Day 8; Part B: Day 1 to Day 58
Secondary outcomes (13)
Pharmacokinetics of ZF874 and its metabolite ZF857 in healthy subjects and PiXZ subjects
maximum plasma concentration
Measured: Part A: Day 1 to Day 3; Part B: Day 1 to Day 29
Pharmacokinetics of ZF874 and its metabolite ZF857 in healthy subjects and PiXZ subjects
time of maximum plasma concentration
Measured: Part A: Day 1 to Day 3; Part B: Day 1 to Day 29
Pharmacokinetics of ZF874 and its metabolite ZF857 in healthy subjects and PiXZ subjects
trough plasma concentration
Measured: Part B: Day 1 to Day 29
Pharmacokinetics of ZF874 and its metabolite ZF857 in healthy subjects and PiXZ subjects
maximum plasma concentration / dose
Measured: Part A: Day 1 to Day 3; Part B: Day 1 to Day 29
Pharmacokinetics of ZF874 and its metabolite ZF857 in healthy subjects and PiXZ subjects
area under the concentration-time curve during the 24 hours post-dose area under curve to 24 hours post-dose
Measured: Part A: Day 1 to Day 2
Pharmacokinetics of ZF874 and its metabolite ZF857 in healthy subjects and PiXZ subjects
area under the concentration-time curve during the 48 hours post-dose area under the concentration-time curve to 48 hours post-dose
Measured: Part A: Day 1 to Day 3
Pharmacokinetics of ZF874 and its metabolite ZF857 in healthy subjects and PiXZ subjects
area under the concentration-time curve during the dosing interval
Measured: Part B: Day 1 to Day 29
Pharmacokinetics of ZF874 and its metabolite ZF857 in healthy subjects and PiXZ subjects
area under the concentration-time curve to last measurable concentration
Measured: Part A: Day 1 to Day 3; Part B: Day 1 to Day 29
Pharmacokinetics of ZF874 and its metabolite ZF857 in healthy subjects and PiXZ subjects
terminal elimination half-life
Measured: Part A: Day 1; Part B: Day 28
Pharmacokinetics of ZF874 and its metabolite ZF857 in healthy subjects and PiXZ subjects
terminal rate constant
Measured: Part A: Day 1; Part B: Day 28
Food effect on the pharmacokinetics of ZF874 and its metabolite ZF857 in healthy subjects
maximum plasma concentration / dose
Measured: Part A: Day 1 to Day 3
Food effect on the pharmacokinetics of ZF874 and its metabolite ZF857 in healthy subjects
area under the concentration-time curve to last measurable concentration
Measured: Part A: Day 1 to Day 3
Food effect on the pharmacokinetics of ZF874 and its metabolite ZF857 in healthy subjects
area under the concentration-time curve extrapolated to infinite time
Measured: Part A: Day 1 to Day 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2020
- Study start3 Aug 2020
- Primary completion12 Sep 2022
- Study completion12 Sep 2022
Why it stopped: Based on the results observed to date, the Sponsor concluded that ZF874 was unlikely to achieve the desired target product profile.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alpha1 Anti-Trypsin DeficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Model description
- This is a double-blind, randomised, placebo-controlled, single ascending and repeat dose trial in healthy subjects and subjects carrying at least one Z-A1AT allele (PiXZ subjects)
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 69 participants (actual)
Sponsor and investigators
- Lead sponsor
- Z Factor Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Hammersmith Medicines Research, Centessa Pharmaceuticals plc
- Responsible party
- Sponsor
- Investigators
- Malcolm Boyce, BSc MD FRCP FFPM, Principal investigator, HMRGiuseppe Fiore, MSc MD, Principal investigator, MAC Clinical Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04443192
- Sponsor's protocol ID
- ZF-0101
- Status last verified
- Sep 2022
- First submitted
- 16 Jun 2020
- Last updated
- 19 Sep 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blind, Randomised, Placebo-controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single Ascending and Repeated Doses of Orally Administered ZF874 in Healthy Volunteers and PiXZ Subjects
- ClinicalTrials.gov ID
- NCT04443192
- Acronym / sponsor ID
- ZF-0101
- Conditions
- Alpha1 Anti-Trypsin Deficiency
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Based on the results observed to date, the Sponsor concluded that ZF874 was unlikely to achieve the desired target product profile.
- Enrolment
- 69 participants (actual)
- Lead sponsor
- Z Factor LimitedIndustry (pharma, biotech, devices)
- Collaborators
- Hammersmith Medicines Research, Centessa Pharmaceuticals plc
- Study start
- 3 Aug 2020 (actual)
- Primary completion
- 12 Sep 2022 (actual)
- Study completion
- 12 Sep 2022 (actual)
- First posted
- 23 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 receive either one or two oral dose(s) of either ZF874 or placebo, in the fasted state in the first 6 groups. There will be up to 7 dose levels of ZF874. In each of the first 6 groups, two subjects (one placebo, one ZF874) are to be dosed in a double-blind manner at least 23 hours prior to the remainder of the group. In the absence of any safety concerns in the leading subjects, the remaining subjects will be dosed, at intervals of at least 10 minutes. 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 Cohort 3, and 12 subjects have already safely received higher doses in Cohorts 4 and 5. In Group 7, all subjects will receive a single dose of ZF874 by mouth, after consuming a high-fat breakfast. All subjects will be screened in the 28 days before their dose of trial medication. Subjects will be resident on ward from 1 day before their dose (Day -1) until 48 hours after dosing (Day 3). They will return for a follow-up visit 5-7 days after their dose (Day 6-8).
Part B: In Group 1, up to 4 subjects will receive twice daily doses of either ZF874 or placebo on 28 consecutive days (up to 3 active: up to 2 placebo). 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 doses will be selected after reviewing the available safety and pharmacokinetic results from previous groups, but will not exceed the doses already given in Part A.
Subjects will be pre-screened to confirm PiXZ genotype within 84 days before their dose of trial medication. Once their genotype is confirmed, they will be screened in the 28 days before their dose of study medication. Subjects will be resident on the ward from 1 day before their first dose (Day -1) until 1 hour after they receive their second dose (Day 2). They will then attend 6 outpatient visits before returning to the ward and be resident from Day 27 until 24 hours after the final dose (Day 29). They will return for further outpatient visits on Days 36, 43 and 50, and for a follow-up visit 28-30 days after their final dose (Day 56-58).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 14
- Model description
- This is a double-blind, randomised, placebo-controlled, single ascending and repeat dose trial in healthy subjects and subjects carrying at least one Z-A1AT allele (PiXZ subjects)
| Arm | Type | Receives |
|---|---|---|
| Part A Cohort 1 - ZF874 | Active comparator | Drug: ZF874Single oral dose of ZF874 by mouth in the fasted state. Dose Level 1 |
| Part A - Placebo to ZF874 - Single Dose | Placebo comparator | Drug: PlaceboSingle oral dose of placebo by mouth in the fasted state |
| Part A Cohort 2 - ZF874 | Active comparator | Drug: ZF874Single oral dose of ZF874 by mouth in the fasted state. Dose Level 2 |
| Part A Cohort 3 - ZF874 | Active comparator | Drug: ZF874Single oral dose of ZF874 by mouth in the fasted state. Dose Level 3 |
| Part A Cohort 4 - ZF874 | Active comparator | Drug: ZF874Single oral dose of ZF874 by mouth in the fasted state. Dose Level 4 |
| Part A - Placebo to ZF874 - Two Doses | Placebo comparator | Drug: PlaceboTwo doses of placebo (12 h apart) by mouth in the fasted state |
| Part A Cohort 5 - ZF874 - Two Doses | Active comparator | Drug: ZF874Two doses of ZF874 (12 h apart) by mouth in the fasted state. Dose Level 5 |
| Part A Cohort 6 - ZF874 - Two Doses | Active comparator | Drug: ZF874Two doses of ZF874 (12 h apart) by mouth in the fasted state. Dose Level 6 |
| Part A Cohort 7 - ZF874 - Single Dose | Active comparator | Drug: ZF874Single oral dose of ZF874 by mouth after consuming a high-fat breakfast. Dose Level 3 |
| Part B Cohort 1 - ZF874 | Active comparator | Drug: ZF874Two doses of ZF874 (12 h apart) by mouth daily for 28 days. |
| Part B Cohort 1 - Placebo to ZF874 | Placebo comparator | Drug: PlaceboTwo doses of placebo (12 h apart) by mouth daily for 28 days. |
| Part B Cohort 2 - ZF874 | Active comparator | Drug: ZF874Two doses of ZF874 (12 h apart) by mouth daily for 28 days. |
| Part B Cohort 3 - ZF874 | Active comparator | Drug: ZF874Two doses of ZF874 (12 h apart) by mouth daily for 28 days. |
| Part B Cohort 4 - ZF874 | Active comparator | Drug: ZF874Two doses of ZF874 (12 h apart) by mouth daily for 28 days. |
Who may qualify
- Ages
- 18 to 72 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (22 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZF874ZF874 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 | Part A Cohort 1 - ZF874, Part A Cohort 2 - ZF874, Part A Cohort 3 - ZF874, Part A Cohort 4 - ZF874, Part A Cohort 5 - ZF874 - Two Doses, Part A Cohort 6 - ZF874 - Two Doses, Part A Cohort 7 - ZF874 - Single Dose, Part B Cohort 1 - ZF874, Part B Cohort 2 - ZF874, Part B Cohort 3 - ZF874, Part B Cohort 4 - ZF874 |
| PlaceboPlacebo to ZF874 | Drug | Part A - Placebo to ZF874 - Single Dose, Part A - Placebo to ZF874 - Two Doses, Part B Cohort 1 - Placebo to ZF874 |
Primary outcome
Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment
Time frame: Part A: Day 1 to Day 8; Part B: Day 1 to Day 58
Safety and tolerability
13 secondary outcomes
Pharmacokinetics of ZF874 and its metabolite ZF857 in healthy subjects and PiXZ subjects
Time frame: Part A: Day 1 to Day 3; Part B: Day 1 to Day 29
Pharmacokinetics of ZF874 and its metabolite ZF857 in healthy subjects and PiXZ subjects
Time frame: Part A: Day 1 to Day 3; Part B: Day 1 to Day 29
Pharmacokinetics of ZF874 and its metabolite ZF857 in healthy subjects and PiXZ subjects
Time frame: Part B: Day 1 to Day 29
Pharmacokinetics of ZF874 and its metabolite ZF857 in healthy subjects and PiXZ subjects
Time frame: Part A: Day 1 to Day 3; Part B: Day 1 to Day 29
Pharmacokinetics of ZF874 and its metabolite ZF857 in healthy subjects and PiXZ subjects
Time frame: Part A: Day 1 to Day 2
Pharmacokinetics of ZF874 and its metabolite ZF857 in healthy subjects and PiXZ subjects
Time frame: Part A: Day 1 to Day 3
Pharmacokinetics of ZF874 and its metabolite ZF857 in healthy subjects and PiXZ subjects
Time frame: Part B: Day 1 to Day 29
Pharmacokinetics of ZF874 and its metabolite ZF857 in healthy subjects and PiXZ subjects
Time frame: Part A: Day 1 to Day 3; Part B: Day 1 to Day 29
Pharmacokinetics of ZF874 and its metabolite ZF857 in healthy subjects and PiXZ subjects
Time frame: Part A: Day 1; Part B: Day 28
Pharmacokinetics of ZF874 and its metabolite ZF857 in healthy subjects and PiXZ subjects
Time frame: Part A: Day 1; Part B: Day 28
Food effect on the pharmacokinetics of ZF874 and its metabolite ZF857 in healthy subjects
Time frame: Part A: Day 1 to Day 3
Food effect on the pharmacokinetics of ZF874 and its metabolite ZF857 in healthy subjects
Time frame: Part A: Day 1 to Day 3
Food effect on the pharmacokinetics of ZF874 and its metabolite ZF857 in healthy subjects
Time frame: Part A: Day 1 to Day 3
Results and safety
The study was stopped early (reason given: Based on the results observed to date, the Sponsor concluded that ZF874 was unlikely to achieve the desired target product profile.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2022.
- Individual participant dataSharing planned: No
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Cystic Fibrosis, Pulmonary Fibrosis
RecruitingPhase 1/2
A Study of TSRA-196 in Adults With PiZZ Alpha-1 Antitrypsin Deficiency (AATD)
Alpha-1 Antitrypsin Deficiency (AATD)
RecruitingPhase 4
Genetic Variation in IgG in Alpha 1 Antitrypsin Deficiency
Alpha 1-Antitrypsin, COPD
Enrolling by invitationObservational study
AATD-Liver Scan Study
Alpha-1 Antitrypsin Deficiency, AATD
RecruitingPhase 3
A Non-inferiority Pharmacokinetic and Safety/Tolerability Study of Two Different Doses of Weekly SC Alpha1-PI 15% Compared With Corresponding Standard IV Alpha1-PI in Participants With Alpha1-Antitrypsin Deficiency (AATD)
Alpha 1 Antitrypsin Deficiency
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Malcolm Boyce, BSc MD FRCP FFPM principal investigator
HMR
Giuseppe Fiore, MSc MD principal investigator
MAC Clinical Research
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ZF874 in people with Alpha1 Anti-Trypsin Deficiency, run by Z Factor Limited at 5 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Based on the results observed to date, the Sponsor concluded that ZF874 was unlikely to achieve the desired target product profile.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment (time frame: Part A: Day 1 to Day 8; Part B: Day 1 to Day 58). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2022.