HAELO: A Phase 3 Study to Evaluate NTLA-2002 in Participants With Hereditary Angioedema (HAE) (HAELO)

HAELO: A Phase 3, Multinational, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of NTLA-2002 in Participants With Hereditary Angioedema (HAE)

This Phase 3 study aims to evaluate the efficacy and safety of NTLA-2002 compared to placebo in participants with HAE.

Study Overview

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

Detailed Description

This is a multinational, multicenter, double-blind, placebo-controlled study in which approximately 60 participants will be randomized in a 2:1 ratio to receive a single IV infusion of NTLA-2002 or placebo. After the Primary Observation Period (Week 1 through Week 28), participants will have the option to receive a blinded, single IV infusion of the opposite treatment. Following the Primary Observation Period, participants will enter the Long-Term Observation Period (76 weeks), for a total of 104 weeks. Including the Screening and Run-In Period, prior to the first blinded dosing, the total study duration is approximately 28 months.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Campbelltown, New South Wales, Australia, 2560
      • Campbelltown Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
    • Parkville, Victoria, Australia, 3050
      • Royal Melbourne Hospital
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2G3
      • University of Alberta
  • Ontario
    • Ottawa, Ontario, Canada, K1H 1E4
      • Ottawa Allergy Research Corporation
• France
  • Grenoble, France, 38043
    • CHU Grenoble-Alpes - Hopital Michallon
  • Lille, France, 59037
    • CHU de Lille - Hopital Claude Huriez
  • Marseille, France, 13385
    • AP-HM - Hopital de la Timone
• Germany
  • Berlin, Germany, 12203
    • Charite Universitaetsmedizin Berlin
  • Frankfurt, Germany, 60590
    • Universitaetsklinikum Frankfurt - Klinikum der Johann Wolfgang Goethe Universitaet
  • Hanover, Germany, 30625
    • Medizinische Hochschule Hannover (MHH)
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Amsterdam UMC - Locatie AMC
• New Zealand
  • Auckland, New Zealand, 1010
    • New Zealand Clinical Research (NZCR)
• South Africa
  • Cape Town, South Africa, 7700
    • University of Cape Town - Lung Institute - Lung Clinical Research Unit
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Cambridge University Hospitals NHS Foundation Trust
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85251
      • Medical Research of Arizona
  • California
    • San Diego, California, United States, 92122
      • University of California, San Diego (UCSD)
    • Santa Monica, California, United States, 90404
      • Raffi Tachdjian MD, Inc
    • Walnut Creek, California, United States, 94598
      • Allergy & Asthma Clinical Research
  • Colorado
    • Centennial, Colorado, United States, 80112
      • IMMUNOe International Research Centers
    • Colorado Springs, Colorado, United States, 80907
      • Asthma & Allergy Associates
  • Florida
    • Tampa, Florida, United States, 33613
      • University of South Florida
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Missouri
    • St Louis, Missouri, United States, 63141
      • Washington University in St. Louis
  • New York
    • Mineola, New York, United States, 11501
      • NYU Langone Health - Long Island
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
  • Ohio
    • Cincinnati, Ohio, United States, 45236
      • Bernstein Clinical Research Center, LLC
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Milton S. Hershey Medical Center
  • Texas
    • Dallas, Texas, United States, 75231
      • AARA Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥16 years
2. Clinical history consistent with HAE-C1INH-Type 1 or -Type 2
3. Ability to provide evidence of HAE attacks (confirmed by the Investigator) to meet the screening requirement
4. Must agree to refrain from the use of long-term prophylactic therapies from the start of the screening period through the end of the Primary Observation Period. PI must be in agreement that it is medically acceptable for the participant to do so.
5. Must have access to, and the ability to use, on-demand medication(s) to treat potential angioedema attacks
6. Adequate chemistry and hematology measures at screening
7. Must agree not to participate in another interventional study for the duration of this trial.
8. Must be capable of providing signed informed consent. Participants 16 to < 18 years of age, whose legal guardian provides informed consent, must provide assent.
9. Must agree to follow contraception requirements

Exclusion Criteria:

1. Concurrent diagnosis of any other type of recurrent angioedema or HAE with normal C1-INH
2. 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: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A: NTLA-2002; Arm A: NTLA-2002 (50 mg; single IV infusion)	Biological: NTLA-2002; CRISPR/Cas9 gene editing system delivered by lipid nanoparticle (LNP) for intravenous (IV) administration
Placebo Comparator: Arm B: Placebo; Arm B: Placebo (saline; single IV infusion)	Biological: Normal Saline IV Administration; The administration of intravenous (IV) normal saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time-normalized number of Investigator-confirmed HAE attacks	From Week 5 through Week 28

Secondary Outcome Measures

Outcome Measure	Time Frame
Time-normalized number of Investigator-confirmed HAE attacks	From Week 1 through Week 28
Time-normalized number of Investigator-confirmed HAE attacks requiring on-demand treatment	From Week 5 through Week 28
Time-normalized number of moderate or severe Investigator-confirmed HAE attacks	From Week 5 through Week 28
Investigator-confirmed HAE attack-free status	From Week 5 through Week 28
Change from baseline to Week 28 in AE-QoL Questionnaire total score	From baseline to Week 28
Responder status, defined as reduction from baseline of at least 50%, 70%, and 90% in time-normalized number of Investigator-confirmed HAE attacks	From Week 5 through Week 28
Time-normalized number of Investigator-confirmed HAE attacks requiring on-demand treatment	from Week 1 through Week 28
Time-normalized number of moderate or severe Investigator-confirmed HAE attacks	From Week 1 through Week 28
Investigator-confirmed HAE attack-free status	From Week 1 through Week 28
Reduction from baseline of at least 50%, 70%, and 90% in time-normalized number of Investigator-confirmed HAE attacks	From Week 1 through Week 28
Long-term prophylaxis-free status	From Week 5 through Week 104
HAE treatment-free status, defined as no usage of long-term prophylaxis or on-demand medication	From Week 5 through Week 104
Complete responder status, defined as zero Investigator-confirmed attacks with no long-term prophylaxis	From Week 5 through Week 104
Reduction in the time-normalized number of Investigator-confirmed HAE attacks after crossover treatment (Week 33 through Week 104) compared to before crossover treatment (Screening through Week 28) in participants randomized to placebo	From Week 33 through Week 104 and from Screening through Week 28

Collaborators and Investigators

• Sponsor: Intellia Therapeutics

Publications and helpful links

General Publications

• Cohn DM, Gurugama P, Longhurst HJ, Aygoren-Pursun E, Craig TJ, Farkas H, Jacobs J, Lumry WR, Magerl M, Peter J, Riedl MA, Maag D, Golden A, Shah MY, Sutherland A, Miller CR, Abdelhady AM, Xu Y, Butler JS, Lebwohl D, Leonard J, Banerji A; HAELO Investigators. Lonvoguran Ziclumeran - In Vivo CRISPR Gene Editing in Hereditary Angioedema. N Engl J Med. 2026 Jun 13. doi: 10.1056/NEJMoa2600931. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2025
• Primary Completion (Actual): February 10, 2026
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: October 7, 2024
• First Submitted That Met QC Criteria: October 8, 2024
• First Posted (Actual): October 9, 2024

Study Record Updates

• Last Update Posted (Actual): July 29, 2026
• Last Update Submitted That Met QC Criteria: July 28, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: HAE; Hereditary Angioedema; NTLA-2002; HAE-C1INH-Type1 or -Type 2
• Additional Relevant MeSH Terms: Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immunologic Deficiency Syndromes; Skin Diseases; Urticaria; Skin Diseases, Vascular; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin and Connective Tissue Diseases; Angioedema; Angioedemas, Hereditary
• Other Study ID Numbers: ITL-2002-CL-301

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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No