Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Trial Review
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Download to PDF
Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT04601051
Registration number
NCT04601051
Ethics application status
Date submitted
19/10/2020
Date registered
23/10/2020
Date last updated
8/09/2023
Titles & IDs
Public title
Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of NTLA-2001 in Patients With Hereditary Transthyretin Amyloidosis With Polyneuropathy (ATTRv-PN) and Patients With Transthyretin Amyloidosis-Related Cardiomyopathy (ATTR-CM)
Query!
Scientific title
Phase 1 Two-Part (Open-label, Single Ascending Dose (Part 1) and Open-label, Single Dose Expansion (Part 2)) Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of NTLA-2001 in Patients With Hereditary Transthyretin Amyloidosis With Polyneuropathy (ATTRv-PN) and Patients With Transthyretin Amyloidosis-Related Cardiomyopathy (ATTR-CM)
Query!
Secondary ID [1]
0
0
2020-002034-32
Query!
Secondary ID [2]
0
0
ITL-2001-CL-001
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Transthyretin-Related (ATTR) Familial Amyloid Polyneuropathy
0
0
Query!
Transthyretin-Related (ATTR) Familial Amyloid Cardiomyopathy
0
0
Query!
Wild-Type Transthyretin Cardiac Amyloidosis
0
0
Query!
Condition category
Condition code
Neurological
0
0
0
0
Query!
Other neurological disorders
Query!
Human Genetics and Inherited Disorders
0
0
0
0
Query!
Other human genetics and inherited disorders
Query!
Metabolic and Endocrine
0
0
0
0
Query!
Other metabolic disorders
Query!
Neurological
0
0
0
0
Query!
Neurodegenerative diseases
Query!
Metabolic and Endocrine
0
0
0
0
Query!
Metabolic disorders
Query!
Intervention/exposure
Study type
Interventional
Query!
Description of intervention(s) / exposure
Other interventions - NTLA-2001
Experimental: Polyneuropathy Part 1: NTLA-2001 - Participants, assigned to one of 4 dose-escalation cohorts, will receive a single dose of NTLA-2001.
Experimental: Polyneuropathy Part 2: NTLA-2001 - Participants, assigned to the dose-expansion cohort, will receive a single dose of NTLA-2001.
Experimental: Cardiomyopathy Part 1 (UK only): NTLA-2001 - Participants, assigned to one of 2 dose-escalation cohorts, will receive a single dose of NTLA-2001.
Experimental: Cardiomyopathy Part 2 (UK only): NTLA-2001 - Participants, assigned to the dose-expansion cohort, will receive a single dose of NTLA-2001.
Experimental: Polyneuropathy Follow-on Dosing (PN Part 1 Dose Level 1 Subjects only): NTLA-2001 - Participants assigned to the follow-on dosing cohort will receive a subsequent dose of NTLA-2001.
Other interventions: NTLA-2001
A clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing system delivered by lipid nanoparticles (LNPs) for intravenous (IV) administration
Query!
Intervention code [1]
0
0
Other interventions
Query!
Comparator / control treatment
Query!
Control group
Query!
Outcomes
Primary outcome [1]
0
0
Number of Participants with Treatment-Emergent Adverse Events
Query!
Assessment method [1]
0
0
Query!
Timepoint [1]
0
0
up to Day 730
Query!
Primary outcome [2]
0
0
Number of Participants with Clinically Significant Clinical Laboratory Test Findings
Query!
Assessment method [2]
0
0
Query!
Timepoint [2]
0
0
up to Day 730
Query!
Primary outcome [3]
0
0
Number of Participants with Clinically Significant Safety Measurements
Query!
Assessment method [3]
0
0
Query!
Timepoint [3]
0
0
up to Day 730
Query!
Primary outcome [4]
0
0
Percent Change from Baseline in Serum TTR (enzyme-linked immunosorbent assay [ELISA])
Query!
Assessment method [4]
0
0
Query!
Timepoint [4]
0
0
up to Day 730
Query!
Primary outcome [5]
0
0
Percent Change from Baseline in Serum Prealbumin
Query!
Assessment method [5]
0
0
Query!
Timepoint [5]
0
0
up to Day 730
Query!
Primary outcome [6]
0
0
Mean Area Under the Plasma Concentration-Time Curve from Time Zero to the Time of the Last Measurable Concentration (AUClast) for DMG-PEG2k, LP000001, Cas9 mRNA, and sgRNA
Query!
Assessment method [6]
0
0
Query!
Timepoint [6]
0
0
up to Day 730
Query!
Primary outcome [7]
0
0
Mean Area Under the Plasma Concentration-Time Curve from Time Zero to Infinity (AUCinf) for DMG-PEG2k, LP000001, Cas9 mRNA, and sgRNA
Query!
Assessment method [7]
0
0
Query!
Timepoint [7]
0
0
up to Day 730
Query!
Primary outcome [8]
0
0
Mean Maximum Concentration (Cmax) for DMG-PEG2k, LP000001, Cas9 mRNA, and sgRNA
Query!
Assessment method [8]
0
0
Query!
Timepoint [8]
0
0
up to Day 730
Query!
Primary outcome [9]
0
0
Mean Time of the Maximum Concentration (Tmax) for DMG-PEG2k, LP000001, Cas9 mRNA, and sgRNA
Query!
Assessment method [9]
0
0
Query!
Timepoint [9]
0
0
up to Day 730
Query!
Primary outcome [10]
0
0
Mean Terminal Half-Life (t½) for DMG-PEG2k, LP000001, Cas9 mRNA, and sgRNA
Query!
Assessment method [10]
0
0
Query!
Timepoint [10]
0
0
up to Day 730
Query!
Primary outcome [11]
0
0
Mean Apparent Clearance (CL) for DMG-PEG2k, LP000001, Cas9 mRNA, and sgRNA
Query!
Assessment method [11]
0
0
Query!
Timepoint [11]
0
0
up to Day 730
Query!
Primary outcome [12]
0
0
Mean Volume of Distribution (Vd) for DMG-PEG2k, LP000001, Cas9 mRNA, and sgRNA
Query!
Assessment method [12]
0
0
Query!
Timepoint [12]
0
0
up to Day 730
Query!
Primary outcome [13]
0
0
Change from Baseline in Anti-Drug Antibody to NTLA-2001 and Anti-Cas9 Protein Antibody to Transgene Product Levels
Query!
Assessment method [13]
0
0
Query!
Timepoint [13]
0
0
up to Day 730
Query!
Secondary outcome [1]
0
0
Polyneuropathy only: Change from Baseline in Familial Amyloid Polyneuropathy (FAP) Stage.
Query!
Assessment method [1]
0
0
Query!
Timepoint [1]
0
0
up to Day 730
Query!
Secondary outcome [2]
0
0
Polyneuropathy only: Change from Baseline in Polyneuropathy Disability (PND) Score
Query!
Assessment method [2]
0
0
Query!
Timepoint [2]
0
0
up to Day 730
Query!
Secondary outcome [3]
0
0
Polyneuropathy only: Change from Baseline in Modified Body Mass Index (mBMI)
Query!
Assessment method [3]
0
0
Query!
Timepoint [3]
0
0
up to Day 730
Query!
Secondary outcome [4]
0
0
Polyneuropathy only: Change from Screening in Neuropathy Impairment Score (NIS)
Query!
Assessment method [4]
0
0
Query!
Timepoint [4]
0
0
up to Day 730
Query!
Secondary outcome [5]
0
0
Polyneuropathy only: Change from Baseline in Modified Neuropathy Impairment Score +7 (mNIS+7)
Query!
Assessment method [5]
0
0
Query!
Timepoint [5]
0
0
up to Day 730
Query!
Secondary outcome [6]
0
0
Polyneuropathy only: Change from Screening in 10-Meter Walk Test (10-MWT)
Query!
Assessment method [6]
0
0
Query!
Timepoint [6]
0
0
up to Day 730
Query!
Secondary outcome [7]
0
0
Polyneuropathy only: Change from Baseline in Norfolk Quality of Life-Diabetic Neuropathy (QOL-DN)
Query!
Assessment method [7]
0
0
Query!
Timepoint [7]
0
0
up to Day 730
Query!
Secondary outcome [8]
0
0
Polyneuropathy only: Change from Baseline in EuroQOL (EQ)-5D-5L
Query!
Assessment method [8]
0
0
Query!
Timepoint [8]
0
0
up to Day 730
Query!
Secondary outcome [9]
0
0
Cardiomyopathy only: Change from Baseline in N-terminal prohormone of brain natriuretic peptide (NT-proBNP)
Query!
Assessment method [9]
0
0
Query!
Timepoint [9]
0
0
up to Day 730
Query!
Secondary outcome [10]
0
0
Cardiomyopathy only: Change from Baseline in hs Troponin T
Query!
Assessment method [10]
0
0
Query!
Timepoint [10]
0
0
up to Day 730
Query!
Secondary outcome [11]
0
0
Cardiomyopathy only: Change from Baseline in Magnetic resonance imaging (MRI)
Query!
Assessment method [11]
0
0
Query!
Timepoint [11]
0
0
up to Day 730
Query!
Secondary outcome [12]
0
0
Cardiomyopathy only: Change from Baseline in Echocardiogram
Query!
Assessment method [12]
0
0
Query!
Timepoint [12]
0
0
up to Day 730
Query!
Secondary outcome [13]
0
0
Cardiomyopathy only: Change from Baseline in Cardio-pulmonary exercise test
Query!
Assessment method [13]
0
0
Query!
Timepoint [13]
0
0
up to Day 730
Query!
Secondary outcome [14]
0
0
Cardiomyopathy only: Change from Baseline in 6-Minute Walk Test (6-MWT)
Query!
Assessment method [14]
0
0
Query!
Timepoint [14]
0
0
up to Day 730
Query!
Secondary outcome [15]
0
0
Cardiomyopathy only: Change from Baseline in New York Heart Association (NYHA) Classification
Query!
Assessment method [15]
0
0
Query!
Timepoint [15]
0
0
up to Day 730
Query!
Secondary outcome [16]
0
0
Cardiomyopathy only: Change from Baseline in Patient-reported outcomes (KCCQ)
Query!
Assessment method [16]
0
0
Query!
Timepoint [16]
0
0
up to Day 730
Query!
Eligibility
Key inclusion criteria
Polyneuropathy
- Male and/or female participants 18 to 80 years of age inclusive, at the time of
signing the informed consent
- Diagnosis of polyneuropathy (PN) due to transthyretin (TTR) amyloidosis (ATTR)
- Must have a body weight of at least 45 kilograms (kg) at Screening visit
- Lack of access to approved treatments for ATTR and/or progression of hereditary
transthyretin amyloidosis with polyneuropathy (ATTRv-PN) despite use of approved
treatment for ATTRv-PN
Polyneuropathy
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
90
Years
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
Key exclusion criteria
- Amyloidosis attributable to non-TTR protein, e.g., amyloid light-chain (AL)
amyloidosis
- Known leptomeningeal transthyretin amyloidosis
- Use of any of the following TTR-directed therapy for ATTR within certain timeframe:
1. Patisiran
2. Inotersen
3. Vutrisiran
4. Tafamidis
5. Diflunisal
6. Doxycycline and/or tauroursodeoxycholic acid
7. Any other investigational agent for the treatment of ATTRv-PN:
- Other protocol defined Inclusion/Exclusion criteria may apply
Cardiomyopathy Inclusion Criteria (UK only):
- Male and/or female participants 18 to 90 years of age inclusive, at the time of
signing the informed consent
- Diagnosis of transthyretin (ATTR) amyloidosis with cardiomyopathy, classified as
hereditary ATTR amyloidosis with cardiomyopathy (ATTRv-CM) or wild type cardiomyopathy
(ATTRwt-CM).
- Must have a body weight of at least 45 kilograms (kg) at Screening visit
- New York Heart Association (NYHA) Class I-III heart failure
- At least 1 prior hospitalization for heart failure and/or clinical evidence of heart
failure.
- Able to complete =150 meters on the 6-minute walk test (6-MWT) during the Screening
period.
Cardiomyopathy Exclusion Criteria (UK only):
- Amyloidosis attributable to non-TTR protein, e.g., amyloid light-chain (AL)
amyloidosis
- Known leptomeningeal transthyretin amyloidosis
- Use of any of the following TTR-directed therapy for ATTR within certain timeframes:
1. Patisiran
2. Inotersen
3. Vutrisiran
4. Tafamidis
5. Diflunisal
6. Doxycycline and/or tauroursodeoxycholic acid
7. Investigational TTR stabilizer (e.g., AG-10)
- Participants with heart failure that in the opinion of the investigator is caused by
ischemic heart disease, hypertension, or uncorrected valvular disease and not
primarily due to transthyretin amyloid cardiomyopathy.
- Participants with a history of sustained ventricular tachycardia or aborted
ventricular fibrillation or with a history of atrioventricular (AV) nodal or
sinoatrial (SA) nodal dysfunction for which a pacemaker is indicated but will not be
placed. Pacemaker or defibrillator placement, initiation of or change in
anti-arrhythmic medication within 28 days prior to study drug administration.
- Other protocol defined Inclusion/Exclusion criteria may apply
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Non-randomised trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Open (masking not used)
Query!
Who is / are masked / blinded?
Query!
Query!
Query!
Query!
Intervention assignment
Other
Query!
Other design features
Query!
Phase
Phase 1
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Active, not recruiting
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
5/11/2020
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
1/08/2026
Query!
Actual
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
72
Query!
Recruitment in Australia
Recruitment state(s)
Query!
Recruitment outside Australia
Country [1]
0
0
France
Query!
State/province [1]
0
0
Paris
Query!
Country [2]
0
0
New Zealand
Query!
State/province [2]
0
0
Auckland
Query!
Country [3]
0
0
Sweden
Query!
State/province [3]
0
0
Umea
Query!
Country [4]
0
0
United Kingdom
Query!
State/province [4]
0
0
London
Query!
Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Query!
Name
Intellia Therapeutics
Query!
Address
Query!
Country
Query!
Ethics approval
Ethics application status
Query!
Summary
Brief summary
This study will be conducted to evaluate the safety, tolerability, pharmacokinetics (PK), and
pharmacodynamics (PD) of NTLA-2001 in participants with hereditary transthyretin amyloidosis
with polyneuropathy (ATTRv-PN) and participants with hereditary transthyretin amyloidosis
with cardiomyopathy (ATTRv-CM) or wild type cardiomyopathy (ATTRwt-CM)
Query!
Trial website
https://clinicaltrials.gov/ct2/show/NCT04601051
Query!
Trial related presentations / publications
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT04601051
Download to PDF