Hereditary Angioedema
Conditions
Keywords
Hereditary Angioedema, NTLA-2002, HAE, HAE-C1INH-Type1 or -Type 2
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.
Interventions
BIOLOGICALNTLA-2002
CRISPR/Cas9 gene editing system delivered by lipid nanoparticle (LNP) for intravenous (IV) administration
BIOLOGICALNormal Saline IV Administration
The administration of intravenous (IV) normal saline
Sponsors
Intellia Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time-normalized number of Investigator-confirmed HAE attacks | From Week 5 through Week 28 |
Secondary
| Measure | Time frame |
|---|---|
| Time-normalized number of Investigator-confirmed HAE attacks requiring on-demand treatment | From Week 5 through Week 28 |
| Time-normalized number of moderate or severe Investigator-confirmed HAE attacks | From Week 5 through Week 28 |
| Investigator-confirmed HAE attack-free status | From Week 5 through Week 28 |
| Change from baseline to Week 28 in AE-QoL Questionnaire total score | 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 | From Week 5 through Week 28 |
| Time-normalized number of Investigator-confirmed HAE attacks | 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 | From Week 1 through Week 28 |
| Long-term prophylaxis-free status | From Week 5 through Week 104 |
| HAE treatment-free status, defined as no usage of long-term prophylaxis or on-demand medication | From Week 5 through Week 104 |
| Complete responder status, defined as zero Investigator-confirmed attacks with no long-term prophylaxis | 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 | From Week 33 through Week 104 and from Screening through Week 28 |
Countries
Australia, Canada, France, Germany, Netherlands, New Zealand, South Africa, United Kingdom, United States
Outcome results
None listed