MAGNITUDE: A Phase 3 Study of NTLA-2001 in Participants With Transthyretin Amyloidosis With Cardiomyopathy (ATTR-CM)

Transthyretin Amyloidosis (ATTR) With Cardiomyopathy Clinical Trial

Official 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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06128629
• Other study ID #: ITL-2001-CL-301
• Status: Recruiting
• Phase: Phase 3
• Start date: December 13, 2023
• Est. completion date: April 2028

Study information

• Verified date: May 2024
• Source: Intellia Therapeutics
• Contact: Trial Manager at Intellia
• Phone: 1-857-285-6200
• Email: medicalinformation[@]intelliatx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To evaluate the efficacy and safety of a single dose of NTLA-2001 compared to placebo in participants with ATTR-CM.

Description:

This is a multinational, multicenter, double-blind, placebo-controlled study in approximately 765 participants, who will be randomized to receive a single infusion of either NTLA-2001 or placebo.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 765
• Est. completion date: April 2028
• Est. primary completion date: December 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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)

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

Related Conditions & MeSH terms

• Amyloid Neuropathies, Familial
• Amyloidosis
• Cardiomyopathies
• Transthyretin Amyloidosis (ATTR) With Cardiomyopathy

Intervention

Biological:
• NTLA-2001
NTLA-2001 (55mg) by IV infusion

Drug:
• Placebo
Normal saline (0.9% NaCl) by IV infusion

Locations

Country	Name	City	State
Australia	Eastern Health - Box Hill Hospital	Box Hill	Victoria
Australia	The Canberra Hospital	Garran
Australia	Fiona Stanley Hospital	Perth
Australia	Westmead Hospital	Westmead
Canada	Alberta Health Services - University of Calgary	Calgary	Alberta
New Zealand	New Zealand Clinical Research	Auckland
New Zealand	New Zealand Clinical Research	Christchurch
United Kingdom	Synexus Midlands Clinical Research Centre	Birmingham
United Kingdom	Synexus Wales Clinical Research Centre	Cardiff
United Kingdom	Synexus Scotland Clinical Research Centre	Glasgow
United Kingdom	Synexus Hexham Clinical Research Centre	Hexham
United Kingdom	Synexus Merseyside Clinical Research Centre	Liverpool
United Kingdom	Richmond Pharmacology	London
United Kingdom	Synexus Manchester Clinical Research Centre	Manchester
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	University of Kentucky Gill Heart Institute	Lexington	Kentucky
United States	Western Greater Los Angeles VA Medical Center	Los Angeles	California
United States	Columbia University Medical Center	New York	New York
United States	MedStar Washington Hospital Center - MedStar Heart and Vascular Institute	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Intellia Therapeutics	Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Canada,  New Zealand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite outcome of cardiovascular (CV) mortality and CV events		Maximum study duration is dependent on event rates and is estimated to be at least 18 months and up to 48 months
Secondary	Change in baseline to month 18 in serum TTR		Baseline, Month 18
Secondary	Change from baseline to month 18 in KCCQ-OS score		Baseline, Month 18