Antitrypsin Deficiency Liver DiseasePhase 1NCT02503683
A Study of an Investigational Drug, ALN-AAT, in Healthy Adult Subjects and Patients With ZZ Type Alpha-1 Antitrypsin Deficiency Liver Disease
A Phase 1 study testing ALN-AAT and Sterile Normal Saline (0.9% NaCl) in people with 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, Tolerability, Pharmacokinetics and Pharmacodynamics of Subcutaneously Administered ALN-AAT in Healthy Adult Subjects and Patients with ZZ Type Alpha-1 Antitrypsin Deficiency Liver Disease. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Antitrypsin Deficiency Liver Disease
- What is being tested?
- ALN-AAT and Sterile Normal Saline (0.9% NaCl)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 26 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 9 Jul 2015to 3 Jan 2018
- 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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Adequate complete blood counts, liver and renal function.
- 12-lead electrocardiogram (ECG) within normal limits
- Female subjects must be of non-childbearing potential; e.g. post-menopausal or pre-menopausal with surgical sterilization
- Male subjects agree to use appropriate contraception
- Willing to provide written informed consent and willing to comply with study requirements
- Nonsmokers for at least 5 years before screening
Who cannot join
- Any uncontrolled or serious disease, or any medical or surgical condition, that may interfere with participation in the clinical study and/or put the subject at significant risk
- Received an investigational agent within 90 days before the first dose of study drug or are in follow-up of another clinical study
- Active serious mental illness or psychiatric disorder requiring current pharmacological intervention
- History or evidence of alcohol or drug abuse within 12 months before screening.
- History of intolerance to SC injection
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1/2, Randomized, Single-blind, Placebo-Controlled, Single Ascending Dose and Multiple Dose, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of Subcutaneously Administered ALN-AAT 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, Tolerability, Pharmacokinetics and Pharmacodynamics of Subcutaneously Administered ALN-AAT in Healthy Adult Subjects and Patients with ZZ Type Alpha-1 Antitrypsin Deficiency Liver Disease.
- Conditions
- Antitrypsin Deficiency Liver Disease
- Being tested
- ALN-AAT, Sterile Normal Saline (0.9% NaCl)
- Keywords
- RNAi therapeutic, AAT, Alpha-1 Antitrypsin Deficiency
- 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.
ALN-AATDrug
Single or multiple doses of ALN-AAT by subcutaneous (sc) injection
Sterile Normal Saline (0.9% NaCl)Drug
calculated volume to match active comparator
| Study group | Role | What they receive |
|---|---|---|
| ALN-AAT | Active comparator | Not described Receives: Drug: ALN-AAT |
| Sterile Normal Saline (0.9% NaCl) | Placebo comparator | Not described Receives: Drug: Sterile Normal Saline (0.9% NaCl) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The safety of ALN-AAT evaluated by the proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs), and AEs leading to study drug discontinuation
Measured: Part A (SAD phase): through day 70; Part B (MAD) phase: through Day 154; Part C: through Day 224
Secondary outcomes (2)
Profile of Pharmacokinetics (PK) of ALN-AAT
Cmax, tmax, AUC, t1/2
Measured: Part A (SAD) phase: up to 21 days; Part B (MAD) phase: up to 105 days; Part C: up to 161 days
The effect of ALN-AAT on serum levels of AAT protein
Measured: Part A (SAD) phase: through day 70; Part B (MAD) phase: through Day 154; Part C: through Day 224
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2015 (estimated)
- Study start9 Jul 2015
- Primary completion3 Jan 2018
- Study completion3 Jan 2018
Why it stopped: Observation of low incidence of asymptomatic, transiently elevated liver enzymes in a subset of study subjects
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alnylam Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Patrick Haslett, MD, Study director, Alnylam Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02503683
- Sponsor's protocol ID
- ALN-AAT-001
- Status last verified
- Jan 2019
- First submitted
- 16 Jul 2015
- Last updated
- 7 Jan 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2, Randomized, Single-blind, Placebo-Controlled, Single Ascending Dose and Multiple Dose, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of Subcutaneously Administered ALN-AAT in Healthy Adult Subjects and Patients With ZZ Type Alpha-1 Antitrypsin Deficiency Liver Disease
- ClinicalTrials.gov ID
- NCT02503683
- Acronym / sponsor ID
- ALN-AAT-001
- Conditions
- Antitrypsin Deficiency Liver Disease
- Keywords
- RNAi therapeutic, AAT, Alpha-1 Antitrypsin Deficiency
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Observation of low incidence of asymptomatic, transiently elevated liver enzymes in a subset of study subjects
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Alnylam PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 9 Jul 2015 (actual)
- Primary completion
- 3 Jan 2018 (actual)
- Study completion
- 3 Jan 2018 (actual)
- First posted
- 21 Jul 2015 (estimated)
- 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, Tolerability, Pharmacokinetics and Pharmacodynamics of Subcutaneously Administered ALN-AAT in Healthy Adult Subjects and Patients with ZZ Type Alpha-1 Antitrypsin Deficiency Liver Disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ALN-AAT | Active comparator | Drug: ALN-AAT |
| Sterile Normal Saline (0.9% NaCl) | Placebo comparator | Drug: Sterile Normal Saline (0.9% NaCl) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Adequate complete blood counts, liver and renal function.
- 12-lead electrocardiogram (ECG) within normal limits
- Female subjects must be of non-childbearing potential; e.g. post-menopausal or pre-menopausal with surgical sterilization
- Male subjects agree to use appropriate contraception
- Willing to provide written informed consent and willing to comply with study requirements
Key exclusion criteria (5 listed)
- Any uncontrolled or serious disease, or any medical or surgical condition, that may interfere with participation in the clinical study and/or put the subject at significant risk
- Received an investigational agent within 90 days before the first dose of study drug or are in follow-up of another clinical study
- Active serious mental illness or psychiatric disorder requiring current pharmacological intervention
- History or evidence of alcohol or drug abuse within 12 months before screening.
- History of intolerance to SC injection
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-AATSingle or multiple doses of ALN-AAT by subcutaneous (sc) injection | Drug | ALN-AAT |
| Sterile Normal Saline (0.9% NaCl)calculated volume to match active comparator | Drug | Sterile Normal Saline (0.9% NaCl) |
Primary outcome
The safety of ALN-AAT evaluated by the proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs), and AEs leading to study drug discontinuation
Time frame: Part A (SAD phase): through day 70; Part B (MAD) phase: through Day 154; Part C: through Day 224
2 secondary outcomes
Profile of Pharmacokinetics (PK) of ALN-AAT
Time frame: Part A (SAD) phase: up to 21 days; Part B (MAD) phase: up to 105 days; Part C: up to 161 days
The effect of ALN-AAT on serum levels of AAT protein
Time frame: Part A (SAD) phase: through day 70; Part B (MAD) phase: through Day 154; Part C: through Day 224
Results and safety
The study was stopped early (reason given: Observation of low incidence of asymptomatic, transiently elevated liver enzymes in a subset of study subjects). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jan 2019.
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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.
Patrick Haslett, MD 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 study testing ALN-AAT and Sterile Normal Saline (0.9% NaCl) in people with 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 6 inclusion and 5 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 7 Jan 2019. 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 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: Observation of low incidence of asymptomatic, transiently elevated liver enzymes in a subset of study subjects). 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?
The safety of ALN-AAT evaluated by the proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs), and AEs leading to study drug discontinuation (time frame: Part A (SAD phase): through day 70; Part B (MAD) phase: through Day 154; Part C: through Day 224). 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 7 Jan 2019.