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    The EU Clinical Trials Register currently displays   42883   clinical trials with a EudraCT protocol, of which   7063   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2018-001362-41
    Sponsor's Protocol Code Number:ALN-AAT02-001
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2019-06-20
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedUK - MHRA
    A.2EudraCT number2018-001362-41
    A.3Full title of the trial
    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
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A 2-Part Safety and Tolerability Study of ALN-AAT02 in Healthy Volunteers and Patients with ZZ Type Alpha-1 Antitrypsin Deficiency Liver Disease
    A.4.1Sponsor's protocol code numberALN-AAT02-001
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorAlnylam Pharmaceuticals, Inc.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportAlnylam Pharmaceuticals, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAlnylam Pharmaceuticals, Inc.
    B.5.2Functional name of contact pointClinical Trials Helpline
    B.5.3 Address:
    B.5.3.1Street Address300 Third Street
    B.5.3.2Town/ cityCambridge
    B.5.3.3Post codeMA 02142
    B.5.3.4CountryUnited States
    B.5.4Telephone number+3120369 78 61
    B.5.6E-mailclinicaltrials@alnylam.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameALN-AAT02
    D.3.2Product code ALN-AAT02
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNALN-77412
    D.3.9.2Current sponsor codeALN-77412
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number189
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for injection
    D.8.4Route of administration of the placeboSubcutaneous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    ZZ Type Alpha-1 Antitrypsin Deficiency Liver Disease
    E.1.1.1Medical condition in easily understood language
    Liver disease associated with Alpha-1 antitrypsin deficiency
    E.1.1.2Therapeutic area Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level PT
    E.1.2Classification code 10001806
    E.1.2Term Alpha-1 anti-trypsin deficiency
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the safety and tolerability of single or multiple doses of ALN-AAT02 when administered to healthy adult subjects and patients with ZZ type of alpha-1 antitrypsin deficiency (PiZZ) AAT deficiency liver disease
    E.2.2Secondary objectives of the trial
    - To assess the effect of ALN-AAT02 on serum levels of alpha-1 antitrypsin (AAT) protein in healthy adult subjects and PiZZ patients
    - To characterize the pharmacokinetics (PK) of ALN-AAT02 in healthy adult subjects and PiZZ patients
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Inclusion Criteria for All Participants in Part A and Part B
    - Male or female, aged 18 to 65 years, inclusive
    - Body mass index (BMI) ≥18.0 kg/m2 and ≤30 kg/m2
    - Nonsmoker for at least 5 years before screening

    Additional Inclusion Criteria for Subjects in Part A
    - AAT levels within normal limits
    - FEV1 ≥85% of predicted and FEV1/forced vital capacity ratio ≥0.7

    Additional Inclusion Criteria for Patients in Part B
    - Documented ZZ type AAT by genotype
    - Liver biopsy performed within 90 days of the first dose of study drug demonstrating liver histopathology consistent with PiZZ AATD liver disease meeting the following criteria:
    a. Presence of diastase-resistant PAS-positive globules in hepatocytes
    b. Ishak fibrosis score of <4
    - Post-bronchodilator FEV1 ≥70% of predicted and diffusing capacity of the lung for carbon monoxide ≥50% of predicted
    - Prior/Concomitant Therapy: If on any maintenance medication regimen, likely, in the opinion of the Investigator, 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)
    E.4Principal exclusion criteria
    Exclusion Criteria for All Participants in Part A and Part B
    - Has known active human immunodeficiency virus (HIV) infection, or evidence of current or chronic hepatitis C virus (HCV) or hepatitis B virus (HBV) infection
    - Has an estimated glomerular filtration of ≤45 mL/min/1.73 m2 at screening
    - Has any clinical safety laboratory result considered clinically significant and unacceptable by the Investigator during screening or on Day 1
    - Received an investigational agent within 30 days or within 5 elimination half-lives, whichever is longer prior to the first dose of study drug, or are in follow-up of another clinical study prior to study enrollment
    - Is unwilling or unable to limit alcohol consumption throughout the course of the study. Alcohol intake of >2 units/day is excluded during the study
    - Has history of alcohol abuse, within the last 12 months before screening, in the opinion of the Investigator
    - Has known history or clinical evidence of drug abuse, within the 12 months before screening.

    Additional Exclusion Criteria for Subjects in Part A
    - Is positive for the rs1303 single nucleotide polymorphism in the SERPINA1 gene
    - Has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >upper limit of normal (ULN) at screening
    - Has total bilirubin above the ULN
    - Has history of asthma or recurrent or chronic lung disease, excluding childhood asthma that has resolved
    - Has history of chronic liver disease from any cause

    Additional Exclusion Criteria for Patients in Part B
    - Has any of the following laboratory parameter assessments at screening:
    a. Alanine aminotransferase or AST ≥1.5× ULN
    b. Total bilirubin >ULN. Patients with elevated total bilirubin that is secondary to documented Gilbert’s syndrome are eligible.
    c. Serum albumin level ≤80% of the LLN
    d. Platelet count ≤100,000 per microliter
    e. International normalized ratio (INR) or prothrombin time (PT) >1.2 of the clinical laboratory reference range
    - Receiving augmentation therapy for AAT deficiency or who have received augmentation therapy within 8 weeks of first dose of study drug
    - Has history of chronic liver disease from any known cause other than ZZ type AAT deficiency
    - Has history of hepatic encephalopathy
    - Has history of gastrointestinal bleeding from esophageal or gastric varices complicating portal hypertension or ascites
    - Has any history of a bleeding disorder or inability to abstain from medications that may interfere with normal blood clotting such that the risk of bleeding following liver biopsy would be increased
    E.5 End points
    E.5.1Primary end point(s)
    Frequency of adverse events (AEs)
    E.5.1.1Timepoint(s) of evaluation of this end point
    Part A: at specified time points through the last postdose follow-up visit (Day 85), or until serum AAT levels return to either ≥80% of mean pre-treatment values, or are within the normal range of the local laboratory, or until the subject has been followed for 12 months following the last dose of study drug and blood AAT values exceed 0.49 g/dL.

    Part B: at specified time points through the last postdose follow-up visit (Day 85), or until serum AAT levels return to either ≥80% of mean pre-treatment values.
    E.5.2Secondary end point(s)
    - Change from baseline in serum levels of AAT in healthy adult subjects and PiZZ patients over the course of the study
    - PK parameters of ALN-AAT02
    E.5.2.1Timepoint(s) of evaluation of this end point
    Part A: at specified time points through the last postdose follow-up visit (Day 85), or until serum AAT levels return to either ≥80% of mean pre-treatment values, or are within the normal range of the local laboratory, or until the subject has been followed for 12 months following the last dose of study drug and blood AAT values exceed 0.49 g/dL.

    Part B: at specified time points through the last postdose follow-up visit (Day 85), or until serum AAT levels return to either ≥80% of mean pre-treatment values.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy No
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans Yes
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA4
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Germany
    United States
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months4
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months4
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 96
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers Yes
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state64
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 80
    F.4.2.2In the whole clinical trial 96
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    As per normal clinical practice.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2018-11-22
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-12-03
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2020-06-05
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