NCT05120830
Active, Not Recruiting
Phase 1
Phase 1/2 Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of NTLA-2002 in Adults With Hereditary Angioedema (HAE)
ConditionsHereditary Angioedema
DrugsBiological NTLA-2002
Overview
- Phase
- Phase 1
- Intervention
- Biological NTLA-2002
- Conditions
- Hereditary Angioedema
- Sponsor
- Intellia Therapeutics
- Enrollment
- 37
- Locations
- 9
- Primary Endpoint
- Safety and tolerability of NTLA-2002 as determined by adverse events (AEs) and dose limiting toxicities (DLTs)
- Status
- Active, Not Recruiting
- Last Updated
- last month
Overview
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).
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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.
Arms & Interventions
Phase 1 Study Arm
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.
Intervention: Biological NTLA-2002
Phase 2 Experimental Study Arm
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.
Intervention: Biological NTLA-2002
Phase 2 Placebo Comparator Study Arm
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.
Intervention: Normal Saline IV Administration
Placebo Crossover and Follow-On Dosing Substudy Arm
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.
Intervention: Biological NTLA-2002
Outcomes
Primary Outcomes
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)
Secondary Outcomes
- 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)
- Change from baseline in total plasma kallikrein protein level(From NTLA-2002 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)
- 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)
Study Sites (9)
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Related News
NTLA-2002 Demonstrates Significant Reduction in Angioedema Attacks via CRISPR-Cas9 Gene Editing- A single dose of NTLA-2002, an investigational CRISPR-Cas9 gene-editing therapy, significantly reduced angioedema attacks in patients with hereditary angioedema (HAE).
- The Phase 2 trial data showed a dose-related reduction in plasma kallikrein levels, with the 50-mg dose reducing kallikrein by 86% from baseline.
- A substantial portion of participants, particularly in the 50-mg group (73%), remained attack-free throughout the 16-week observation period without needing additional intervention.
- NTLA-2002 was generally well-tolerated, with mostly mild-to-moderate adverse events, supporting its further investigation in a Phase 3 trial.NTLA-2002 Shows Promise as Functional Cure for Hereditary Angioedema in Phase 2 Trial- Phase 2 trial results show NTLA-2002 significantly reduces swelling attacks in hereditary angioedema (HAE) patients, with up to 80% attack reduction at the 50 mg dose.
- A substantial portion of patients receiving NTLA-2002 experienced complete attack-free periods, with some remaining attack-free through the latest assessments.
- NTLA-2002 was generally well-tolerated, with no serious side effects reported, suggesting a favorable safety profile for this gene-editing therapy.
- Intellia Therapeutics has initiated a Phase 3 trial based on these positive results, potentially redefining the treatment paradigm for HAE.Intellia Therapeutics Initiates Phase 3 Trial of NTLA-2002 for Hereditary Angioedema- Intellia Therapeutics has dosed the first patient in its Phase 3 HAELO trial evaluating NTLA-2002 for hereditary angioedema (HAE).
- The HAELO trial is a global, randomized, double-blind, placebo-controlled study involving 60 adults with Type I or Type II HAE.
- NTLA-2002, a single-dose CRISPR-based therapy, targets the _KLKB1_ gene to reduce plasma kallikrein activity and prevent HAE attacks.
- Intellia anticipates completing enrollment in the second half of 2025 and plans for a potential U.S. launch in 2027, pending regulatory approval.