Hereditary Angioedema
Conditions
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).
Interventions
BIOLOGICALBiological NTLA-2002
CRISPR/Cas9 gene editing system delivered by LNP for IV administration
The administration of IV normal saline
Sponsors
Intellia Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Phase 1 is an open label non-randomized study Phase 2 is a randomized, double-blind, placebo-controlled study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age \>18 years 2. Diagnosis of HAE Types I or II 3. Ability to provide evidence of HAE attacks to meet the screening requirement 4. Subjects must have access to, and the ability to use, ≥ 1 acute medication(s) to treat angioedema attacks. 5. Adequate chemistry and hematology measures at screening 6. Subjects must agree not to participate in another interventional study for the duration of this trial. 7. Subjects must be capable of providing signed informed consent
Exclusion criteria
1. Concurrent diagnosis of any other type of recurrent angioedema 2. Subjects who 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability of NTLA-2002 as determined by adverse events (AEs) and dose limiting toxicities (DLTs) | From NTLA-2002 infusion up to week 104 post-infusion | (Phase 1 only) |
| Number of HAE attacks per month (Weeks 1-16) | From study drug infusion up to week 16 post-infusion | (Phase 2 only) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in total plasma kallikrein protein level | From NTLA-2002 infusion up to week 104 post-infusion | (Phase 1 \& 2) |
| Plasma and urine concentrations for DMG-PEG2k, LP000001, Cas9 mRNA, and sgRNA | From NTLA-2002 infusion up to week 104 post-infusion | (Phase 1 \& 2) |
| Safety and tolerability of NTLA-2002 as determined by AEs | From study drug infusion up to week 104 post-infusion | (Phase 2 only) |
| Number of HAE attacks per month (Weeks 5-16) | From week 6 post-infusion up to week 16 post-infusion | (Phase 2 only) |
| 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 | (Phase 2 only) |
Countries
Australia, France, Germany, Netherlands, New Zealand, United Kingdom
Outcome results
None listed