Clinical trial NCT06634420: HAELO: A Phase 3 Study to Evaluate NTLA-2002 in Participants With Hereditary Angioedema (HAE)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Hereditary Angioedema
Keywords: Hereditary Angioedema
NTLA-2002
HAE
HAE-C1INH-Type1 or -Type 2
Lead sponsor: Intellia Therapeutics
Sponsor class: INDUSTRY
First posted: 2024-10-09
Enrollment: 60
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Time-normalized number of Investigator-confirmed HAE attacks
timeFrame: From Week 5 through Week 28
Secondary outcomes:
measure: Time-normalized number of Investigator-confirmed HAE attacks requiring on-demand treatment
timeFrame: From Week 5 through Week 28
measure: Time-normalized number of moderate or severe Investigator-confirmed HAE attacks
timeFrame: From Week 5 through Week 28
measure: Investigator-confirmed HAE attack-free status
timeFrame: From Week 5 through Week 28
measure: Change from baseline to Week 28 in AE-QoL Questionnaire total score
timeFrame: From baseline to Week 28
measure: Responder status, defined as reduction from baseline of at least 50%, 70%, and 90% in time-normalized number of Investigator-confirmed HAE attacks
timeFrame: From Week 5 through Week 28
measure: Time-normalized number of Investigator-confirmed HAE attacks
timeFrame: From Week 1 through Week 28
measure: Time-normalized number of Investigator-confirmed HAE attacks requiring on-demand treatment
timeFrame: from Week 1 through Week 28
measure: Time-normalized number of moderate or severe Investigator-confirmed HAE attacks
timeFrame: From Week 1 through Week 28
measure: Investigator-confirmed HAE attack-free status
timeFrame: From Week 1 through Week 28
measure: Reduction from baseline of at least 50%, 70%, and 90% in time-normalized number of Investigator-confirmed HAE attacks
timeFrame: From Week 1 through Week 28
measure: Long-term prophylaxis-free status
timeFrame: From Week 5 through Week 104
measure: HAE treatment-free status, defined as no usage of long-term prophylaxis or on-demand medication
timeFrame: From Week 5 through Week 104
measure: Complete responder status, defined as zero Investigator-confirmed attacks with no long-term prophylaxis
timeFrame: From Week 5 through Week 104
measure: 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
timeFrame: From Week 33 through Week 104 and from Screening through Week 28
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Medical Research of Arizona
state: Arizona
city: San Diego
country: United States
facility: University of California, San Diego (UCSD)
state: California
city: Santa Monica
country: United States
facility: Raffi Tachdjian MD, Inc
state: California
city: Walnut Creek
country: United States
facility: Allergy & Asthma Clinical Research
state: California
city: Centennial
country: United States
facility: IMMUNOe International Research Centers
state: Colorado
city: Colorado Springs
country: United States
facility: Asthma & Allergy Associates
state: Colorado
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Detriot
country: United States
facility: Henry Ford Health System
state: Michigan
city: St. Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: Mineola
country: United States
facility: NYU Langone Health - Long Island
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Cincinnati
country: United States
facility: Bernstein Clinical Research Center, LLC
state: Ohio
city: Columbus
country: United States
facility: Optimed Research, LTD
state: Ohio
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Dallas
country: United States
facility: AARA Research Center
state: Texas
city: Campbelltown
country: Australia
facility: Campbelltown Hospital
state: New South Wales
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Ottawa
country: Canada
facility: Ottawa Allergy Research Corporation
state: Ontario
city: Grenoble
country: France
facility: CHU Grenoble-Alpes - Hopital Michallon
city: Lille
country: France
facility: CHU de Lille - Hopital Claude Huriez
city: Marseille
country: France
facility: AP-HM - Hopital de la Timone
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin Berlin
city: Frankfurt
country: Germany
facility: Universitaetsklinikum Frankfurt - Klinikum der Johann Wolfgang Goethe Universitaet
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover (MHH)
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC - Locatie AMC
city: Auckland
country: New Zealand
facility: New Zealand Clinical Research (NZCR)
city: Cape Town
country: South Africa
facility: University of Cape Town - Lung Institute - Lung Clinical Research Unit
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust
Study officials:
References: