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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06128629




Registration number
NCT06128629
Ethics application status
Date submitted
8/11/2023
Date registered
13/11/2023
Date last updated
12/06/2024

Titles & IDs
Public title
MAGNITUDE: A Phase 3 Study of NTLA-2001 in Participants With Transthyretin Amyloidosis With Cardiomyopathy (ATTR-CM)
Scientific title
MAGNITUDE: A Phase 3, Multinational, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of NTLA-2001 in Participants With Transthyretin Amyloidosis With Cardiomyopathy (ATTR-CM)
Secondary ID [1] 0 0
ITL-2001-CL-301
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Transthyretin Amyloidosis (ATTR) With Cardiomyopathy 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Neurological 0 0 0 0
Other neurological disorders
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders
Metabolic and Endocrine 0 0 0 0
Metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - NTLA-2001
Treatment: Drugs - Placebo

Experimental: NTLA-2001 - Single intravenous (IV) infusion of NTLA-2001

Placebo comparator: Placebo - Single IV infusion of normal saline


Treatment: Other: NTLA-2001
NTLA-2001 (55mg) by IV infusion

Treatment: Drugs: Placebo
Normal saline (0.9% NaCl) by IV infusion
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Composite outcome of cardiovascular (CV) mortality and CV events
Timepoint [1] 0 0
Maximum study duration is dependent on event rates and is estimated to be at least 18 months and up to 48 months
Secondary outcome [1] 0 0
Change in baseline to month 18 in serum TTR
Timepoint [1] 0 0
Baseline, Month 18
Secondary outcome [2] 0 0
Change from baseline to month 18 in KCCQ-OS score
Timepoint [2] 0 0
Baseline, Month 18

Eligibility
Key inclusion criteria
* Documented diagnosis of ATTR amyloidosis with cardiomyopathy
* Medical history of heart failure (HF)
* Symptoms of HF are optimally managed and clinically stable within 28 days prior to administration of study intervention
* Screening NT-proBNP, a blood marker of HF severity, greater than or equal to 1000 pg/mL (or greater than or equal to 2000 pg/mL if participant has known atrial fibrillation)
Minimum age
18 Years
Maximum age
90 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* New York Heart Association (NYHA) Class IV HF
* Polyneuropathy Disability score of IV (confined to wheelchair or bed)
* Has hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection
* History of active malignancy within 3 years prior to screening
* RNA silencer therapy (patisiran, inotersen and/or eplontersen) within 12 months prior to dosing. Any prior vutrisiran use is not allowed
* Initiation of tafamidis within 6 months prior to study dosing
* Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m^2
* Liver failure
* Uncontrolled blood pressure
* Unable or unwilling to take vitamin A supplementation for the duration of the study

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/12/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/04/2028
Actual
Sample size
Target
765
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Eastern Health - Box Hill Hospital - Box Hill
Recruitment hospital [2] 0 0
The Canberra Hospital - Garran
Recruitment hospital [3] 0 0
Fiona Stanley Hospital - Perth
Recruitment hospital [4] 0 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 0 0
- Box Hill
Recruitment postcode(s) [2] 0 0
- Garran
Recruitment postcode(s) [3] 0 0
- Perth
Recruitment postcode(s) [4] 0 0
- Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
District of Columbia
Country [3] 0 0
United States of America
State/province [3] 0 0
Kentucky
Country [4] 0 0
United States of America
State/province [4] 0 0
Michigan
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
Texas
Country [7] 0 0
Canada
State/province [7] 0 0
Alberta
Country [8] 0 0
New Zealand
State/province [8] 0 0
Auckland
Country [9] 0 0
New Zealand
State/province [9] 0 0
Christchurch
Country [10] 0 0
United Kingdom
State/province [10] 0 0
Birmingham
Country [11] 0 0
United Kingdom
State/province [11] 0 0
Cardiff
Country [12] 0 0
United Kingdom
State/province [12] 0 0
Glasgow
Country [13] 0 0
United Kingdom
State/province [13] 0 0
Hexham
Country [14] 0 0
United Kingdom
State/province [14] 0 0
Liverpool
Country [15] 0 0
United Kingdom
State/province [15] 0 0
London
Country [16] 0 0
United Kingdom
State/province [16] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Intellia Therapeutics
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Regeneron Pharmaceuticals
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
To evaluate the efficacy and safety of a single dose of NTLA-2001 compared to placebo in participants with ATTR-CM.
Trial website
https://clinicaltrials.gov/study/NCT06128629
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Trial Manager at Intellia
Address 0 0
Country 0 0
Phone 0 0
1-857-285-6200
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06128629