NTLA-2002 in Adults With Hereditary Angioedema (HAE) (NTLA-2002)

Phase 1/2 Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of NTLA-2002 in Adults With Hereditary Angioedema (HAE)

This study will be conducted to evaluate the safety, tolerability, activity, pharmacokinetics, and pharmacodynamics of NTLA-2002 in adults with Hereditary Angioedema (HAE).

Study Overview

• Status: Active, not recruiting
• Conditions: Hereditary Angioedema
• Intervention / Treatment: Biological: Biological NTLA-2002; Other: Normal Saline IV Administration

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Trial Manager at Intellia; Phone Number: 833-888-0387; Email: clinicalscience@intelliatx.com

Study Locations

• Australia
  • Campbelltown, Australia
    • Clinical Trial Site
• France
  • Grenoble, France
    • Clinical Trial Site
  • Lille, France
    • Clinical Trial Site
  • Paris, France
    • Clinical Trial Site
• Germany
  • Berlin, Germany
    • Clinical Trial Site
  • Frankfurt, Germany
    • Clinical Trial Site
• Netherlands
  • Amsterdam, Netherlands
    • Clinical Trial Site
• New Zealand
  • Auckland, New Zealand
    • Clinical Trial Site
• United Kingdom
  • Cambridge, United Kingdom
    • Clinical Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age >18 years
2. Diagnosis of HAE Types I or II
3. Ability to provide evidence of HAE attacks to meet the screening requirement
4. Subjects must have access to, and the ability to use, ≥ 1 acute medication(s) to treat angioedema attacks.
5. Adequate chemistry and hematology measures at screening
6. Subjects must agree not to participate in another interventional study for the duration of this trial.
7. Subjects must be capable of providing signed informed consent

Exclusion Criteria:

1. Concurrent diagnosis of any other type of recurrent angioedema
2. Subjects who have known negative reaction or hypersensitivity to any lipid nanoparticles (LNP) component.
3. Any condition that, in the Investigator's opinion, could adversely affect the safety of the subject.
4. Unwilling to comply with study procedures.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1 Study Arm; Participants assigned to 1 of 3 dose-escalation cohorts will receive a single dose of NTLA-2002 on Day 1 and will then be followed for 104 weeks. Primary observation period is 16 weeks.	Biological: Biological NTLA-2002; CRISPR/Cas9 gene editing system delivered by LNP for IV administration
Experimental: Phase 2 Experimental Study Arm; Participants randomized to NTLA-2002 (2 dose levels), will receive a single dose of NTLA-2002 on Day 1 and will then be followed for 104 weeks. Primary observation period is 16 weeks.	Biological: Biological NTLA-2002; CRISPR/Cas9 gene editing system delivered by LNP for IV administration
Placebo Comparator: Phase 2 Placebo Comparator Study Arm; Participants randomized to placebo will receive IV normal saline on Day 1 and will then be followed for up to 104 weeks. Primary observation period is 16 weeks.	Other: Normal Saline IV Administration; The administration of IV normal saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of NTLA-2002 as determined by adverse events (AEs) and dose limiting toxicities (DLTs)	(Phase 1 only)	From NTLA-2002 infusion up to week 104 post-infusion
Number of HAE attacks per month (Weeks 1-16)	(Phase 2 only)	From study drug infusion up to week 16 post-infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in total plasma kallikrein protein level	(Phase 1 & 2)	From NTLA-2002 infusion up to week 104 post-infusion
Plasma and urine concentrations for DMG-PEG2k, LP000001, Cas9 mRNA, and sgRNA	(Phase 1 & 2)	From NTLA-2002 infusion up to week 104 post-infusion
Safety and tolerability of NTLA-2002 as determined by AEs	(Phase 2 only)	From study drug infusion up to week 104 post-infusion
Number of HAE attacks per month (Weeks 5-16)	(Phase 2 only)	From week 6 post-infusion up to week 16 post-infusion
Number of HAE attacks per month requiring acute therapy (Weeks 1-16, Weeks 5-16)	(Phase 2 only)	From study drug infusion up to week 16 post-infusion

Collaborators and Investigators

• Sponsor: Intellia Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2021
• Primary Completion (Estimated): April 15, 2024
• Study Completion (Estimated): December 15, 2025

Study Registration Dates

• First Submitted: November 3, 2021
• First Submitted That Met QC Criteria: November 12, 2021
• First Posted (Actual): November 15, 2021

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 7, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Vascular; Hypersensitivity; Urticaria; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Angioedema; Angioedemas, Hereditary
• Other Study ID Numbers: ITL-2002-CL-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No