Hereditary AngioedemaPhase 3NCT06634420
HAELO: A Phase 3 Study to Evaluate NTLA-2002 in Participants With Hereditary Angioedema (HAE)
A Phase 3 study testing NTLA-2002 and Normal Saline IV Administration in people with Hereditary Angioedema, run by Intellia Therapeutics at 29 sites in 9 countries.
Trial summary
This Phase 3 study aims to evaluate the efficacy and safety of NTLA-2002 compared to placebo in participants with HAE. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Hereditary Angioedema
- What is being tested?
- NTLA-2002 and Normal Saline IV Administration
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 29 sitesin 9 countries
- Study dates
- 15 Jan 2025to Sep 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age ≥16 years
- Clinical history consistent with HAE-C1INH-Type 1 or -Type 2
- Ability to provide evidence of HAE attacks (confirmed by the Investigator) to meet the screening requirement
- 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.
- Must have access to, and the ability to use, on-demand medication(s) to treat potential angioedema attacks
- Adequate chemistry and hematology measures at screening
Show all 9Show fewer
- Must agree not to participate in another interventional study for the duration of this trial.
- Must be capable of providing signed informed consent. Participants 16 to < 18 years of age, whose legal guardian provides informed consent, must provide assent.
- Must agree to follow contraception requirements
Who cannot join
- Concurrent diagnosis of any other type of recurrent angioedema or HAE with normal C1-INH
- 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.
Trial locations and contacts
29 sites in 9 countries.
29 sites in 9 countries
United States14 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
IMMUNOe International Research Centers
Centennial, Colorado, 80112
Bernstein Clinical Research Center, LLC
Cincinnati, Ohio, 45236
Asthma & Allergy Associates
Colorado Springs, Colorado, 80907
AARA Research Center
Dallas, Texas, 75231
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033
NYU Langone Health - Long Island
Mineola, New York, 11501
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
University of California, San Diego (UCSD)
San Diego, California, 92122
Raffi Tachdjian MD, Inc
Santa Monica, California, 90404
Medical Research of Arizona
Scottsdale, Arizona, 85251
Washington University in St. Louis
St Louis, Missouri, 63141
University of South Florida
Tampa, Florida, 33613
Allergy & Asthma Clinical Research
Walnut Creek, California, 94598
Australia3 sites
Campbelltown Hospital
Campbelltown, New South Wales, 2560
The Alfred Hospital
Melbourne, Victoria, 3004
Royal Melbourne Hospital
Parkville, Victoria, 3050
France3 sites
CHU Grenoble-Alpes - Hopital Michallon
Grenoble, 38043
CHU de Lille - Hopital Claude Huriez
Lille, 59037
AP-HM - Hopital de la Timone
Marseille, 13385
Germany3 sites
Charite Universitaetsmedizin Berlin
Berlin, 12203
Universitaetsklinikum Frankfurt - Klinikum der Johann Wolfgang Goethe Universitaet
Frankfurt, 60590
Medizinische Hochschule Hannover (MHH)
Hanover, 30625
Canada2 sites
University of Alberta
Edmonton, Alberta, T6G 2G3
Ottawa Allergy Research Corporation
Ottawa, Ontario, K1H 1E4
South Africa1 site
University of Cape Town - Lung Institute - Lung Clinical Research Unit
Cape Town, 7700
United Kingdom1 site
Cambridge University Hospitals NHS Foundation Trust
Cambridge, CB2 0QQ
About this study
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)
This Phase 3 study aims to evaluate the efficacy and safety of NTLA-2002 compared to placebo in participants with HAE.
Read the 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.
- Conditions
- Hereditary Angioedema
- Being tested
- NTLA-2002, Normal Saline IV Administration
- Keywords
- Hereditary Angioedema, NTLA-2002, HAE, HAE-C1INH-Type1 or -Type 2
- Medical subject headings
- Angioedemas, Hereditary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NTLA-2002Biological
CRISPR/Cas9 gene editing system delivered by lipid nanoparticle (LNP) for intravenous (IV) administration
Normal Saline IV AdministrationBiological
The administration of intravenous (IV) normal saline
| Study group | Role | What they receive |
|---|---|---|
| Arm A: NTLA-2002 | Active comparator | Arm A: NTLA-2002 (50 mg; single IV infusion) Receives: Biological: NTLA-2002 |
| Arm B: Placebo | Placebo comparator | Arm B: Placebo (saline; single IV infusion) Receives: Biological: Normal Saline IV Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time-normalized number of Investigator-confirmed HAE attacks
Measured: From Week 5 through Week 28
Secondary outcomes (14)
Time-normalized number of Investigator-confirmed HAE attacks requiring on-demand treatment
Measured: From Week 5 through Week 28
Time-normalized number of moderate or severe Investigator-confirmed HAE attacks
Measured: From Week 5 through Week 28
Investigator-confirmed HAE attack-free status
Measured: From Week 5 through Week 28
Change from baseline to Week 28 in AE-QoL Questionnaire total score
Measured: 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
Measured: From Week 5 through Week 28
Time-normalized number of Investigator-confirmed HAE attacks
Measured: From Week 1 through Week 28
Time-normalized number of Investigator-confirmed HAE attacks requiring on-demand treatment
Measured: from Week 1 through Week 28
Time-normalized number of moderate or severe Investigator-confirmed HAE attacks
Measured: From Week 1 through Week 28
Investigator-confirmed HAE attack-free status
Measured: 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
Measured: From Week 1 through Week 28
Long-term prophylaxis-free status
Measured: From Week 5 through Week 104
HAE treatment-free status, defined as no usage of long-term prophylaxis or on-demand medication
Measured: From Week 5 through Week 104
Complete responder status, defined as zero Investigator-confirmed attacks with no long-term prophylaxis
Measured: 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
Measured: From Week 33 through Week 104 and from Screening through Week 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2024
- Study start15 Jan 2025
- Primary completion10 Feb 2026
- Study completionSep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hereditary AngioedemaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Intellia Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06634420
- Sponsor's protocol ID
- ITL-2002-CL-301
- Status last verified
- May 2026
- First submitted
- 7 Oct 2024
- Last updated
- 8 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 42294842
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT06634420
- Acronym / sponsor ID
- ITL-2002-CL-301
- Conditions
- Hereditary Angioedema
- Keywords
- Hereditary Angioedema, NTLA-2002, HAE, HAE-C1INH-Type1 or -Type 2
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Intellia TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 15 Jan 2025 (actual)
- Primary completion
- 10 Feb 2026 (actual)
- Study completion
- Sep 2027 (estimated)
- First posted
- 9 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A: NTLA-2002 | Active comparator | Biological: NTLA-2002Arm A: NTLA-2002 (50 mg; single IV infusion) |
| Arm B: Placebo | Placebo comparator | Biological: Normal Saline IV AdministrationArm B: Placebo (saline; single IV infusion) |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Age ≥16 years
- Clinical history consistent with HAE-C1INH-Type 1 or -Type 2
- Ability to provide evidence of HAE attacks (confirmed by the Investigator) to meet the screening requirement
- 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.
- Must have access to, and the ability to use, on-demand medication(s) to treat potential angioedema attacks
Key exclusion criteria (4 listed)
- Concurrent diagnosis of any other type of recurrent angioedema or HAE with normal C1-INH
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NTLA-2002CRISPR/Cas9 gene editing system delivered by lipid nanoparticle (LNP) for intravenous (IV) administration | Biological | Arm A: NTLA-2002 |
| Normal Saline IV AdministrationThe administration of intravenous (IV) normal saline | Biological | Arm B: Placebo |
Primary outcome
Time-normalized number of Investigator-confirmed HAE attacks
Time frame: From Week 5 through Week 28
14 secondary outcomes
Time-normalized number of Investigator-confirmed HAE attacks requiring on-demand treatment
Time frame: From Week 5 through Week 28
Time-normalized number of moderate or severe Investigator-confirmed HAE attacks
Time frame: From Week 5 through Week 28
Investigator-confirmed HAE attack-free status
Time frame: From Week 5 through Week 28
Change from baseline to Week 28 in AE-QoL Questionnaire total score
Time frame: 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
Time frame: From Week 5 through Week 28
Time-normalized number of Investigator-confirmed HAE attacks
Time frame: From Week 1 through Week 28
Time-normalized number of Investigator-confirmed HAE attacks requiring on-demand treatment
Time frame: from Week 1 through Week 28
Time-normalized number of moderate or severe Investigator-confirmed HAE attacks
Time frame: From Week 1 through Week 28
Investigator-confirmed HAE attack-free status
Time frame: 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
Time frame: From Week 1 through Week 28
Long-term prophylaxis-free status
Time frame: From Week 5 through Week 104
HAE treatment-free status, defined as no usage of long-term prophylaxis or on-demand medication
Time frame: From Week 5 through Week 104
Complete responder status, defined as zero Investigator-confirmed attacks with no long-term prophylaxis
Time frame: 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
Time frame: From Week 33 through Week 104 and from Screening through Week 28
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2026.
- Derived from this study: PubMed 42294842Cohn 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
29 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing NTLA-2002 and Normal Saline IV Administration in people with Hereditary Angioedema, run by Intellia Therapeutics at 29 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 8 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in United States, Australia, France, Germany, Canada and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time-normalized number of Investigator-confirmed HAE attacks (time frame: From Week 5 through Week 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06634420, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2026.