NTLA-2002 in Adults With Hereditary Angioedema (HAE) (NTLA-2002)

• ClinicalTrials.gov Identifier: NCT05120830
• Recruitment Status: Active, not recruiting
• First Posted: November 15, 2021
• Last Update Posted: March 12, 2024
• Sponsor: Intellia Therapeutics
• Information provided by (Responsible Party): Intellia Therapeutics

Tracking Information

• First Submitted Date: November 3, 2021
• First Posted Date: November 15, 2021
• Last Update Posted Date: March 12, 2024
• Actual Study Start Date: December 10, 2021
• Estimated Primary Completion Date: April 15, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 28, 2022)

• 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)

Original Primary Outcome Measures (submitted: November 12, 2021)

• Safety and tolerability of NTLA-2002 as determined by adverse events (AEs) [ Time Frame: From NTLA-2002 infusion up to week 104 post-infusion ]
  (Phase 1 only)
• Estimated efficacy as determined by measurement of change from baseline in HAE attack rate [ Time Frame: From study drug infusion up to week 104 post-infusion, primary observation period change in attack rate 16 weeks post-infusion ]
  (Phase 2 only)

Current Secondary Outcome Measures (submitted: April 28, 2022)

• Change from baseline in total plasma kallikrein protein level [ Time Frame: 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 [ Time Frame: From NTLA-2002 infusion up to week 104 post-infusion ]
  (Phase 1 & 2)
• Safety and tolerability of NTLA-2002 as determined by AEs [ Time Frame: From study drug infusion up to week 104 post-infusion ]
  (Phase 2 only)
• Number of HAE attacks per month (Weeks 5-16) [ Time Frame: 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) [ Time Frame: From study drug infusion up to week 16 post-infusion ]
  (Phase 2 only)

Original Secondary Outcome Measures (submitted: November 12, 2021)

• Evaluate the efficacy of NTLA-2002 as determined by HAE attack rate (Weeks 1-16, Weeks 5-16 [ Time Frame: From NTLA-2002 infusion up to week 104 post-infusion ]
  (Phase 1 only)
• Change from baseline in total plasma kallikrein protein level [ Time Frame: From NTLA-2002 infusion up to week 104 post-infusion ]
  (Phase 1 only)
• Plasma and urine concentrations for DMG-PEG2k, LP000001, Cas9 mRNA, and sgRNA [ Time Frame: From NTLA-2002 infusion up to week 104 post-infusion ]
  (Phase 1 only)
• Safety and tolerability of NTLA-2002 as determined by AEs [ Time Frame: From study drug infusion up to week 104 post-infusion ]
  (Phase 2 only)
• Change from baseline in HAE attack rate (Weeks 5-16) [ Time Frame: From study drug infusion up to week 104 post-infusion ]
  (Phase 2 only)
• Change from baseline in number of HAE attacks requiring acute therapy (Weeks 1-16, Weeks 5-16) [ Time Frame: From study drug infusion up to week 16 post-infusion ]
  (Phase 2 only)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: NTLA-2002 in Adults With Hereditary Angioedema (HAE)
• Official Title: Phase 1/2 Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of NTLA-2002 in Adults With Hereditary Angioedema (HAE)
• 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2

Study Design

Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double (Participant, Investigator)
Masking Description:

Phase 1 is an open label non-randomized study Phase 2 is a randomized, double-blind, placebo-controlled study

Primary Purpose: Treatment

• Condition: Hereditary Angioedema

Intervention

• Biological: Biological NTLA-2002
  CRISPR/Cas9 gene editing system delivered by LNP for IV administration
• Other: Normal Saline IV Administration
  The administration of IV normal saline

Study Arms

• Experimental: 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: Biological NTLA-2002
• Experimental: 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: Biological NTLA-2002
• Placebo Comparator: 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: Other: Normal Saline IV Administration

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: March 7, 2024): 37
• Original Estimated Enrollment (submitted: November 12, 2021): 55
• Estimated Study Completion Date: December 15, 2025
• Estimated Primary Completion Date: April 15, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, France, Germany, Netherlands, New Zealand, United Kingdom

Administrative Information

• NCT Number: NCT05120830
• Other Study ID Numbers: ITL-2002-CL-001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Intellia Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: Intellia Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Intellia Therapeutics
• Verification Date: March 2024