Back to resultsA Study of an Investigational Drug, ALN-AAT, in Healthy Adult Subjects and Patients With ZZ Type Alpha-1 Antitrypsin Deficiency Liver Disease
Primary Purpose
Antitrypsin Deficiency Liver Disease
Status
Terminated
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
ALN-AAT
Sterile Normal Saline (0.9% NaCl)
Sponsored by
About this trial
This is an interventional treatment trial for Antitrypsin Deficiency Liver Disease focused on measuring RNAi therapeutic, AAT, Alpha-1 Antitrypsin Deficiency
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Sites / Locations
- Richmond Pharmacology, Ltd.
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
ALN-AAT
Sterile Normal Saline (0.9% NaCl)
Arm Description
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Profile of Pharmacokinetics (PK) of ALN-AAT
Cmax, tmax, AUC, t1/2
The effect of ALN-AAT on serum levels of AAT protein
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02503683
Brief Title
A Study of an Investigational Drug, ALN-AAT, in Healthy Adult Subjects and Patients With ZZ Type Alpha-1 Antitrypsin Deficiency Liver Disease
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
Study Type
Interventional
2. Study Status
Record Verification Date
January 2019
Overall Recruitment Status
Terminated
Why Stopped
Observation of low incidence of asymptomatic, transiently elevated liver enzymes in a subset of study subjects
Study Start Date
July 9, 2015 (Actual)
Primary Completion Date
January 3, 2018 (Actual)
Study Completion Date
January 3, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alnylam Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Antitrypsin Deficiency Liver Disease
Keywords
RNAi therapeutic, AAT, Alpha-1 Antitrypsin Deficiency
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
26 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ALN-AAT
Arm Type
Active Comparator
Arm Title
Sterile Normal Saline (0.9% NaCl)
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
ALN-AAT
Intervention Description
Single or multiple doses of ALN-AAT by subcutaneous (sc) injection
Intervention Type
Drug
Intervention Name(s)
Sterile Normal Saline (0.9% NaCl)
Intervention Description
calculated volume to match active comparator
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
Profile of Pharmacokinetics (PK) of ALN-AAT
Description
Cmax, tmax, AUC, t1/2
Time Frame
Part A (SAD) phase: up to 21 days; Part B (MAD) phase: up to 105 days; Part C: up to 161 days
Title
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Patrick Haslett, MD
Organizational Affiliation
Alnylam Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Richmond Pharmacology, Ltd.
City
London
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
A Study of an Investigational Drug, ALN-AAT, in Healthy Adult Subjects and Patients With ZZ Type Alpha-1 Antitrypsin Deficiency Liver Disease
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