Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

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
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
4/11/2024

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)
ACT,NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
The Canberra Hospital - Garran
Recruitment hospital [2] 0 0
Westmead Hospital - Westmead
Recruitment hospital [3] 0 0
Cairns Hospital - Cairns
Recruitment hospital [4] 0 0
Eastern Health - Box Hill Hospital - Box Hill
Recruitment hospital [5] 0 0
Fiona Stanley Hospital - Perth
Recruitment hospital [6] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 0 0
- Garran
Recruitment postcode(s) [2] 0 0
- Westmead
Recruitment postcode(s) [3] 0 0
- Cairns
Recruitment postcode(s) [4] 0 0
- Box Hill
Recruitment postcode(s) [5] 0 0
- Perth
Recruitment postcode(s) [6] 0 0
- Adelaide
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
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
District of Columbia
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Kentucky
Country [8] 0 0
United States of America
State/province [8] 0 0
Maryland
Country [9] 0 0
United States of America
State/province [9] 0 0
Massachusetts
Country [10] 0 0
United States of America
State/province [10] 0 0
Michigan
Country [11] 0 0
United States of America
State/province [11] 0 0
Minnesota
Country [12] 0 0
United States of America
State/province [12] 0 0
New York
Country [13] 0 0
United States of America
State/province [13] 0 0
Ohio
Country [14] 0 0
United States of America
State/province [14] 0 0
Oregon
Country [15] 0 0
United States of America
State/province [15] 0 0
Pennsylvania
Country [16] 0 0
United States of America
State/province [16] 0 0
South Carolina
Country [17] 0 0
United States of America
State/province [17] 0 0
Texas
Country [18] 0 0
United States of America
State/province [18] 0 0
Virginia
Country [19] 0 0
Argentina
State/province [19] 0 0
Buenos Aires
Country [20] 0 0
Canada
State/province [20] 0 0
Alberta
Country [21] 0 0
Denmark
State/province [21] 0 0
Aarhus
Country [22] 0 0
Denmark
State/province [22] 0 0
Copenhagen
Country [23] 0 0
France
State/province [23] 0 0
Rennes
Country [24] 0 0
France
State/province [24] 0 0
Toulouse
Country [25] 0 0
Germany
State/province [25] 0 0
Heidelberg
Country [26] 0 0
Italy
State/province [26] 0 0
Firenze
Country [27] 0 0
Italy
State/province [27] 0 0
Genova
Country [28] 0 0
Italy
State/province [28] 0 0
Pavia
Country [29] 0 0
Italy
State/province [29] 0 0
Trieste
Country [30] 0 0
New Zealand
State/province [30] 0 0
Auckland
Country [31] 0 0
New Zealand
State/province [31] 0 0
Christchurch
Country [32] 0 0
Singapore
State/province [32] 0 0
Singapore
Country [33] 0 0
Spain
State/province [33] 0 0
Barcelona
Country [34] 0 0
Spain
State/province [34] 0 0
Majadahonda
Country [35] 0 0
Spain
State/province [35] 0 0
Málaga
Country [36] 0 0
Sweden
State/province [36] 0 0
Stockholm
Country [37] 0 0
Sweden
State/province [37] 0 0
Umea
Country [38] 0 0
Taiwan
State/province [38] 0 0
New Taipei City
Country [39] 0 0
Taiwan
State/province [39] 0 0
Taipei
Country [40] 0 0
United Kingdom
State/province [40] 0 0
Birmingham
Country [41] 0 0
United Kingdom
State/province [41] 0 0
Cardiff
Country [42] 0 0
United Kingdom
State/province [42] 0 0
Glasgow
Country [43] 0 0
United Kingdom
State/province [43] 0 0
Hexham
Country [44] 0 0
United Kingdom
State/province [44] 0 0
Liverpool
Country [45] 0 0
United Kingdom
State/province [45] 0 0
London
Country [46] 0 0
United Kingdom
State/province [46] 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