NTLA-2002 in Adults With Hereditary Angioedema (HAE)

NCT05120830 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: ITL-2002-CL-001
• Study Type: interventional
• Target: 37
• Locations: 6 countries
• Sites: 9

Brief Summary

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

Conditions

Hereditary Angioedema

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• Change from baseline in total plasma kallikrein protein level

  From NTLA-2002 infusion up to week 104 post-infusion

• Plasma and urine concentrations for DMG-PEG2k, LP000001, Cas9 mRNA, and sgRNA

  From NTLA-2002 infusion up to week 104 post-infusion

• Safety and tolerability of NTLA-2002 as determined by AEs

  From study drug infusion up to week 104 post-infusion

• Number of HAE attacks per month (Weeks 5-16)

  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)

  From study drug infusion up to week 16 post-infusion

Study Arms (4)

Phase 1 Study Arm

EXPERIMENTAL

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

Phase 2 Experimental Study Arm

EXPERIMENTAL

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

Phase 2 Placebo Comparator Study Arm

PLACEBO COMPARATOR

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

Placebo Crossover and Follow-On Dosing Substudy Arm

EXPERIMENTAL

Participants assigned to this Substudy Arm (participants who previously received either 25mg or placebo only) will have the opportunity to receive a single dose of NTLA-2002 (50mg) and will then be followed for 52 weeks.

Biological: Biological NTLA-2002

Interventions

Biological NTLA-2002 BIOLOGICAL

CRISPR/Cas9 gene editing system delivered by LNP for IV administration

Phase 1 Study Arm; Phase 2 Experimental Study Arm; Placebo Crossover and Follow-On Dosing Substudy Arm

Normal Saline IV Administration OTHER

The administration of IV normal saline

Phase 2 Placebo Comparator Study Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Intellia Therapeutics: lead

Study Sites (9)

Clinical Trial Site

Campbelltown, Australia

Location

Clinical Trial Site

Grenoble, France

Location

Clinical Trial Site

Lille, France

Location

Clinical Trial Site

Paris, France

Location

Clinical Trial Site

Berlin, Germany

Location

Clinical Trial Site

Frankfurt, Germany

Location

Clinical Trial Site

Amsterdam, Netherlands

Location

Clinical Trial Site

Auckland, New Zealand

Location

Clinical Trial Site

Cambridge, United Kingdom

Location

Related Publications (2)

• Cohn DM, Gurugama P, Magerl M, Katelaris CH, Launay D, Bouillet L, Petersen RS, Lindsay K, Aygoren-Pursun E, Maag D, Butler JS, Shah MY, Golden A, Xu Y, Abdelhady AM, Lebwohl D, Longhurst HJ. CRISPR-Based Therapy for Hereditary Angioedema. N Engl J Med. 2025 Jan 30;392(5):458-467. doi: 10.1056/NEJMoa2405734. Epub 2024 Oct 24.

  PMID: 39445704 DERIVED

• Longhurst HJ, Lindsay K, Petersen RS, Fijen LM, Gurugama P, Maag D, Butler JS, Shah MY, Golden A, Xu Y, Boiselle C, Vogel JD, Abdelhady AM, Maitland ML, McKee MD, Seitzer J, Han BW, Soukamneuth S, Leonard J, Sepp-Lorenzino L, Clark ED, Lebwohl D, Cohn DM. CRISPR-Cas9 In Vivo Gene Editing of KLKB1 for Hereditary Angioedema. N Engl J Med. 2024 Feb 1;390(5):432-441. doi: 10.1056/NEJMoa2309149.

  PMID: 38294975 DERIVED

MeSH Terms

Conditions

Angioedemas, Hereditary

Condition Hierarchy (Ancestors)

Angioedema; Vascular Diseases; Cardiovascular Diseases; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Immunologic Deficiency Syndromes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Phase 1 is an open label non-randomized study Phase 2 is a randomized, double-blind, placebo-controlled study
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2021
• First Posted: November 15, 2021
• Study Start: December 10, 2021
• Primary Completion: April 4, 2024
• Study Completion (Estimated): July 1, 2026
• Last Updated: March 24, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3); NZ (1); AU (1); NL (1); DE (2); GB (1)