Hereditary AngioedemaPhase 1/2NTLA-2002NCT05120830
NTLA-2002 in Adults With Hereditary Angioedema (HAE)
A Phase 1/2 study testing Biological NTLA-2002 and Normal Saline IV Administration in people with Hereditary Angioedema, run by Intellia Therapeutics at 9 sites in 6 countries.
Trial summary
This study will be conducted to evaluate the safety, tolerability, activity, pharmacokinetics, and pharmacodynamics of NTLA-2002 in adults with Hereditary Angioedema (HAE). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hereditary Angioedema
- What is being tested?
- Biological 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
- 37 participants
- Where
- 9 sitesin 6 countries
- Study dates
- 10 Dec 2021to 31 May 2027
- Phase
- Phase 1/2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
9 sites in 6 countries.
9 sites in 6 countries
France3 sites
Clinical Trial Site
Grenoble
Clinical Trial Site
Lille
Clinical Trial Site
Paris
About this study
Official title: 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).
- Conditions
- Hereditary Angioedema
- Being tested
- Biological NTLA-2002, Normal Saline IV Administration
- Medical subject headings
- Angioedemas, Hereditary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biological NTLA-2002Biological
CRISPR/Cas9 gene editing system delivered by LNP for IV administration
Normal Saline IV AdministrationOther
The administration of IV normal saline
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Biological: Biological NTLA-2002 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability of NTLA-2002 as determined by adverse events (AEs) and dose limiting toxicities (DLTs)
(Phase 1 only)
Measured: From NTLA-2002 infusion up to week 104 post-infusion
Number of HAE attacks per month (Weeks 1-16)
(Phase 2 only)
Measured: From study drug infusion up to week 16 post-infusion
Secondary outcomes (5)
Change from baseline in total plasma kallikrein protein level
(Phase 1 \& 2)
Measured: 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)
Measured: From NTLA-2002 infusion up to week 104 post-infusion
Safety and tolerability of NTLA-2002 as determined by AEs
(Phase 2 only)
Measured: From study drug infusion up to week 104 post-infusion
Number of HAE attacks per month (Weeks 5-16)
(Phase 2 only)
Measured: 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)
Measured: From study drug infusion up to week 16 post-infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2021
- Study start10 Dec 2021
- Primary completion4 Apr 2024
- Study completion31 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 37 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
- NCT05120830
- Sponsor's protocol ID
- ITL-2002-CL-001
- Acronym
- NTLA-2002
- Status last verified
- Sep 2026
- First submitted
- 3 Nov 2021
- Last updated
- 25 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 39445704Longhurst 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.
PubMed 38294975
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1/2 Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of NTLA-2002 in Adults With Hereditary Angioedema (HAE)
- ClinicalTrials.gov ID
- NCT05120830
- Acronym / sponsor ID
- NTLA-2002 / ITL-2002-CL-001
- Conditions
- Hereditary Angioedema
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Intellia TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 10 Dec 2021 (actual)
- Primary completion
- 4 Apr 2024 (actual)
- Study completion
- 31 May 2027 (estimated)
- First posted
- 15 Nov 2021 (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 study will be conducted to evaluate the safety, tolerability, activity, pharmacokinetics, and pharmacodynamics of NTLA-2002 in adults with Hereditary Angioedema (HAE).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Phase 1 Study Arm | Experimental | Biological: Biological NTLA-2002Participants 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. |
| Phase 2 Experimental Study Arm | Experimental | Biological: Biological NTLA-2002Participants 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. |
| Phase 2 Placebo Comparator Study Arm | Placebo comparator | Other: Normal Saline IV AdministrationParticipants 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. |
| Placebo Crossover and Follow-On Dosing Substudy Arm | Experimental | Biological: Biological NTLA-2002Participants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (4 listed)
- 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.
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 |
|---|---|---|
| Biological NTLA-2002CRISPR/Cas9 gene editing system delivered by LNP for IV administration | Biological | Phase 1 Study Arm, Phase 2 Experimental Study Arm, Placebo Crossover and Follow-On Dosing Substudy Arm |
| Normal Saline IV AdministrationThe administration of IV normal saline | Other | Phase 2 Placebo Comparator Study Arm |
Primary outcome
Safety and tolerability of NTLA-2002 as determined by adverse events (AEs) and dose limiting toxicities (DLTs)
Time frame: From NTLA-2002 infusion up to week 104 post-infusion
(Phase 1 only)
Number of HAE attacks per month (Weeks 1-16)
Time frame: From study drug infusion up to week 16 post-infusion
(Phase 2 only)
5 secondary outcomes
Change from baseline in total plasma kallikrein protein level
Time frame: From NTLA-2002 infusion up to week 104 post-infusion
Plasma and urine concentrations for DMG-PEG2k, LP000001, Cas9 mRNA, and sgRNA
Time frame: From NTLA-2002 infusion up to week 104 post-infusion
Safety and tolerability of NTLA-2002 as determined by AEs
Time frame: From study drug infusion up to week 104 post-infusion
Number of HAE attacks per month (Weeks 5-16)
Time frame: 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)
Time frame: From study drug infusion up to week 16 post-infusion
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 25 Sep 2026.
- Derived from this study: PubMed 39445704Cohn 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.
- Derived from this study: PubMed 38294975Longhurst 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.
- 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.
9 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Biological NTLA-2002 and Normal Saline IV Administration in people with Hereditary Angioedema, run by Intellia Therapeutics at 9 sites in 6 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 7 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 25 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in France, Germany, Australia, Netherlands, New Zealand and 1 more country. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Safety and tolerability of NTLA-2002 as determined by adverse events (AEs) and dose limiting toxicities (DLTs) (time frame: From NTLA-2002 infusion up to week 104 post-infusion). The study lists 2 primary outcomes in all. 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 NCT05120830, which also lists 2 linked publications.
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 25 Sep 2026.