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

• ClinicalTrials.gov Identifier: NCT06128629
• Recruitment Status: Recruiting
• First Posted: November 13, 2023
• Last Update Posted: May 14, 2024
• Sponsor: Intellia Therapeutics
• Collaborator: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Intellia Therapeutics

Tracking Information

• First Submitted Date: November 8, 2023
• First Posted Date: November 13, 2023
• Last Update Posted Date: May 14, 2024
• Actual Study Start Date: December 13, 2023
• Estimated Primary Completion Date: December 2027 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 8, 2023): Composite outcome of cardiovascular (CV) mortality and CV events [ Time Frame: Maximum study duration is dependent on event rates and is estimated to be at least 18 months and up to 48 months ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 8, 2023)

• Change in baseline to month 18 in serum TTR [ Time Frame: Baseline, Month 18 ]
• Change from baseline to month 18 in KCCQ-OS score [ Time Frame: Baseline, Month 18 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: MAGNITUDE: A Phase 3 Study of NTLA-2001 in Participants With Transthyretin Amyloidosis With Cardiomyopathy (ATTR-CM)
• 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)
• Brief Summary: To evaluate the efficacy and safety of a single dose of NTLA-2001 compared to placebo in participants with ATTR-CM.
• Detailed 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.
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Participants will be randomized in a 2:1 ratio to NTLA-2001 or placebo

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

• Condition: 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

Study Arms

• Experimental: NTLA-2001
  Single intravenous (IV) infusion of NTLA-2001
  Intervention: Biological: NTLA-2001
• Placebo Comparator: Placebo
  Single IV infusion of normal saline
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 8, 2023): 765
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 2028
• Estimated Primary Completion Date: December 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 90 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Trial Manager at Intellia; 1-857-285-6200 ext 6; medicalinformation@intelliatx.com

• Listed Location Countries: Australia, Canada, New Zealand, United Kingdom, United States

Administrative Information

• NCT Number: NCT06128629
• Other Study ID Numbers: ITL-2001-CL-301
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Intellia Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: Intellia Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Regeneron Pharmaceuticals
• Investigators: Not Provided
• PRS Account: Intellia Therapeutics
• Verification Date: May 2024