ZZ Type Alpha-1 Antitrypsin Deficiency Liver DiseasePhase 1/2NCT03767829
A Study of ALN-AAT02 in Healthy Participants and Participants With ZZ Type Alpha-1 Antitrypsin Deficiency Liver Disease
A Phase 1/2 study testing ALN-AAT02 in people with ZZ Type Alpha-1 Antitrypsin Deficiency Liver Disease, run by Alnylam Pharmaceuticals at 1 site in United Kingdom.
Trial summary
The purpose of this study is to evaluate the safety and tolerability of single or multiple doses of ALN-AAT02. The study will be conducted in 2 sequential phases in which Part A will be a single-ascending dose (SAD) phase in healthy participants, and Part B will be a multiple-ascending dose (MAD) phase in participants… Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- ZZ Type Alpha-1 Antitrypsin Deficiency Liver Disease
- What is being tested?
- ALN-AAT02
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 5 Dec 2018to 25 Jun 2020
- Phase
- Phase 1/2
- 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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male or female, aged 18 to 65 years, inclusive;
- Has normal 12-lead electrocardiogram (ECG);
- Has body mass index (BMI) between 18 and 30 kg/m^2, inclusive;
- Has been a nonsmoker for at least 5 years before screening;
- Part A only: Has Alpha-1 antitrypsin (AAT) levels within normal limits;
- Part A only: Has adequate Forced Expiratory Volume in 1 second (FEV1) and adequate FEV1/forced vital capacity ratio;
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- Part B only: Has documented ZZ type AAT by genotype;
- Part B only: Has liver biopsy within 90 days of the first dose of study drug demonstrating ZZ type alpha-1 antitrypsin deficiency (PiZZ AATD) liver disease;
- Part B only: Has adequate post-bronchodilator FEV1 and adequate diffusing capacity of the lung for carbon monoxide;
- Part B only: If on any maintenance medication, is likely to be able to remain on a stable medication regimen for the duration of the study (no new medications within 30 days prior to first dose of study drug).
Who cannot join
- Has known human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis B virus (HBV) infection;
- Has clinically significant abnormal laboratory results;
- Received an experimental drug within 30 days of dosing;
- Has a history of multiple drug allergies or history of allergic reaction to an oligonucleotide or N-acetylgalactosamine (GalNAc);
- Part A only: Has estimated glomerular filtration equal to or below 60 mL/min/1.73 m^2 at screening;
- Part A only: Has a history of asthma or recurrent or chronic lung disease, excluding resolved childhood asthma;
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- Part A only: Has a history of chronic liver disease;
- Part B only: Has estimated glomerular filtration equal to or below 45 mL/min/1.73 m^2 at screening;
- Part B only: Received an augmentation therapy for AAT deficiency within 8 weeks of first dose of study drug;
- Part B only: Has a history of chronic liver disease from any known cause other than ZZ type AAT deficiency;
- Part B only: Has a history of hepatic encephalopathy;
- Part B only: Has a history of gastrointestinal bleeding or ascites.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1/2, Randomized, Double-blind, Placebo-controlled, Single-ascending and Multiple-dose, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of Subcutaneously Administered ALN-AAT02 in Healthy Adult Subjects and Patients With ZZ Type Alpha-1 Antitrypsin Deficiency Liver Disease
The purpose of this study is to evaluate the safety and tolerability of single or multiple doses of ALN-AAT02. The study will be conducted in 2 sequential phases in which Part A will be a single-ascending dose (SAD) phase in healthy participants, and Part B will be a multiple-ascending dose (MAD) phase in participants with ZZ type alpha-1 antitrypsin deficiency (PiZZ) and biopsy-proven alpha-1 antitrypsin (AAT) deficiency-associated liver disease.
- Being tested
- ALN-AAT02, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ALN-AAT02Drug
ALN-AAT02 will be administered subcutaneously (SC) at dose levels planned for Part A.
PlaceboDrug
Sterile normal saline (0.9% NaCl) matching volume of ALN-AAT02 doses will be administered SC.
ALN-AAT02Drug
ALN-AAT02 will be administered subcutaneously (SC). Part B dose levels to be determined upon review of data from Part A.
| Study group | Role | What they receive |
|---|---|---|
| Part A: SAD: ALN-AAT02 | Experimental | Participants will be administered a single dose of ALN-AAT02. Receives: Drug: ALN-AAT02 |
| Part A: SAD: Placebo | Placebo comparator | Participants will be administered a single dose of matching placebo. Receives: Drug: Placebo |
| Part B: MAD: ALN-AAT02 | Experimental | Participants will be administered multiple doses of ALN-AAT02. Receives: Drug: ALN-AAT02 |
| Part B: MAD: Placebo | Placebo comparator | Participants will be administered multiple doses of matching placebo. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants with Treatment Emergent Adverse Events (TEAEs)
Measured: Part A: up to approximately 12 months; Part B: up to approximately 18 months
Secondary outcomes (7)
Change From Baseline in Serum Levels of Alpha-1 Antitrypsin (AAT)
Measured: Part A: baseline up to Day 85 and every 84 days up to approximately 12 months; Part B: baseline up to Day 169 and every 84 days up to approximately 18 months
Maximum Observed Plasma Concentration (Cmax) for ALN-AAT02
Measured: Part A: Days 1, 2, 3, 8 and 15; Part B: Days 1, 2, 3, 29, 85, 86 and 87
Time to Reach Cmax (tmax) for ALN-AAT02
Measured: Part A: Days 1, 2, 3, 8 and 15; Part B: Days 1, 2, 3, 29, 85, 86 and 87
Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ALN-AAT02
Measured: Part A: Days 1, 2, 3, 8 and 15; Part B: Days 1, 2, 3, 29, 85, 86 and 87
Apparent Terminal Elimination Half-life (t1/2) for ALN-AAT02
Measured: Part A: Days 1, 2, 3, 8 and 15; Part B: Days 1, 2, 3, 29, 85, 86 and 87
Fraction Eliminated in Urine (fe) of ALN-AAT02
Measured: Part A: Day 1; Part B: Days 1 and 85
Amount of Full Length Drug Excreted in Urine (Ae) of ALN-AAT02
Measured: Part A: Day 1; Part B: Days 1 and 85
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2018
- Study start5 Dec 2018
- Primary completion25 Jun 2020
- Study completion25 Jun 2020
Why it stopped: The sponsor decided not to proceed with Part B for business reasons.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ZZ Type Alpha-1 Antitrypsin Deficiency Liver DiseaseStudies of the same condition, open and under way.
- More trials run by Alnylam PharmaceuticalsThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alnylam Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Alnylam Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03767829
- Sponsor's protocol ID
- ALN-AAT02-001
- Other IDs
- 2018-001362-41, 2018
- Status last verified
- Apr 2021
- First submitted
- 5 Dec 2018
- Last updated
- 27 Apr 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2, Randomized, Double-blind, Placebo-controlled, Single-ascending and Multiple-dose, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of Subcutaneously Administered ALN-AAT02 in Healthy Adult Subjects and Patients With ZZ Type Alpha-1 Antitrypsin Deficiency Liver Disease
- ClinicalTrials.gov ID
- NCT03767829
- Acronym / sponsor ID
- ALN-AAT02-001
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The sponsor decided not to proceed with Part B for business reasons.
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Alnylam PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 5 Dec 2018 (actual)
- Primary completion
- 25 Jun 2020 (actual)
- Study completion
- 25 Jun 2020 (actual)
- First posted
- 7 Dec 2018 (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.
The purpose of this study is to evaluate the safety and tolerability of single or multiple doses of ALN-AAT02. The study will be conducted in 2 sequential phases in which Part A will be a single-ascending dose (SAD) phase in healthy participants, and Part B will be a multiple-ascending dose (MAD) phase in participants with ZZ type alpha-1 antitrypsin deficiency (PiZZ) and biopsy-proven alpha-1 antitrypsin (AAT) deficiency-associated liver disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Part A: SAD: ALN-AAT02 | Experimental | Drug: ALN-AAT02Participants will be administered a single dose of ALN-AAT02. |
| Part A: SAD: Placebo | Placebo comparator | Drug: PlaceboParticipants will be administered a single dose of matching placebo. |
| Part B: MAD: ALN-AAT02 | Experimental | Drug: ALN-AAT02Participants will be administered multiple doses of ALN-AAT02. |
| Part B: MAD: Placebo | Placebo comparator | Drug: PlaceboParticipants will be administered multiple doses of matching placebo. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Male or female, aged 18 to 65 years, inclusive;
- Has normal 12-lead electrocardiogram (ECG);
- Has body mass index (BMI) between 18 and 30 kg/m^2, inclusive;
- Has been a nonsmoker for at least 5 years before screening;
- Part A only: Has Alpha-1 antitrypsin (AAT) levels within normal limits;
Key exclusion criteria (12 listed)
- Has known human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis B virus (HBV) infection;
- Has clinically significant abnormal laboratory results;
- Received an experimental drug within 30 days of dosing;
- Has a history of multiple drug allergies or history of allergic reaction to an oligonucleotide or N-acetylgalactosamine (GalNAc);
- Part A only: Has estimated glomerular filtration equal to or below 60 mL/min/1.73 m^2 at screening;
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 |
|---|---|---|
| ALN-AAT02ALN-AAT02 will be administered subcutaneously (SC) at dose levels planned for Part A. | Drug | Part A: SAD: ALN-AAT02 |
| PlaceboSterile normal saline (0.9% NaCl) matching volume of ALN-AAT02 doses will be administered SC. | Drug | Part A: SAD: Placebo, Part B: MAD: Placebo |
| ALN-AAT02ALN-AAT02 will be administered subcutaneously (SC). Part B dose levels to be determined upon review of data from Part A. | Drug | Part B: MAD: ALN-AAT02 |
Primary outcome
Percentage of Participants with Treatment Emergent Adverse Events (TEAEs)
Time frame: Part A: up to approximately 12 months; Part B: up to approximately 18 months
7 secondary outcomes
Change From Baseline in Serum Levels of Alpha-1 Antitrypsin (AAT)
Time frame: Part A: baseline up to Day 85 and every 84 days up to approximately 12 months; Part B: baseline up to Day 169 and every 84 days up to approximately 18 months
Maximum Observed Plasma Concentration (Cmax) for ALN-AAT02
Time frame: Part A: Days 1, 2, 3, 8 and 15; Part B: Days 1, 2, 3, 29, 85, 86 and 87
Time to Reach Cmax (tmax) for ALN-AAT02
Time frame: Part A: Days 1, 2, 3, 8 and 15; Part B: Days 1, 2, 3, 29, 85, 86 and 87
Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ALN-AAT02
Time frame: Part A: Days 1, 2, 3, 8 and 15; Part B: Days 1, 2, 3, 29, 85, 86 and 87
Apparent Terminal Elimination Half-life (t1/2) for ALN-AAT02
Time frame: Part A: Days 1, 2, 3, 8 and 15; Part B: Days 1, 2, 3, 29, 85, 86 and 87
Fraction Eliminated in Urine (fe) of ALN-AAT02
Time frame: Part A: Day 1; Part B: Days 1 and 85
Amount of Full Length Drug Excreted in Urine (Ae) of ALN-AAT02
Time frame: Part A: Day 1; Part B: Days 1 and 85
Results and safety
The study was stopped early (reason given: The sponsor decided not to proceed with Part B for business reasons.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2021.
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.
Medical Director study director
Alnylam Pharmaceuticals
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ALN-AAT02 in people with ZZ Type Alpha-1 Antitrypsin Deficiency Liver Disease, run by Alnylam Pharmaceuticals at 1 site 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 10 inclusion and 12 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 27 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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: The sponsor decided not to proceed with Part B for business reasons.). 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?
Percentage of Participants with Treatment Emergent Adverse Events (TEAEs) (time frame: Part A: up to approximately 12 months; Part B: up to approximately 18 months). 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 27 Apr 2021.