HAE Hereditary Angioedema
Conditions
Interventions
Non Clinical:
Informed Consent
Recivew of Inclusion/Exclusion Criteria
Demographic data and medical history
Concomitant medications use
HAE attack history
AE-QoL
Adverse events
Clinical:
Physical exa
Sponsors
Intellia Therapeutics, Inc.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as protocol waivers or exemptions, are not permitted. Participants are eligible to be included in the study only if all of the following criteria apply: 1. Subjects >= 18 years of age at the time of signing the informed consent. 2. Documented diagnosis of HAE (Type I or II) confirmed by laboratory assessment of functional C1-INH level and C1-INH concentration: a. For HAE Type I: Both functional C1-INH level AND C1-INH concentration should be = 1 acute medication(s) to treat angioedema attacks. 6. Subjects must meet the following laboratory criteria during Screening: a. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total bilirubin (see exception for Gilbert's Syndrome below) 60 mL/min/1.73 m2 as measured by the Modification of Diet
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: 1. Use of ecallantide from 1 week prior to the start of Screening through the 16-week primary observation period. 2. Use of C1 esterase inhibitor (C1-INH) for HAE within 5 half-lives of the agent before initiation of the Phase 2 Screening/Run-In period, i.e., 24-hour washout is required before starting the Screening/Run-In period after the use of rabbit purified C1-INH (ruconest), and 4-day washout is required before starting the Screening/Run-In period after the use of human plasma purified C1-INH (berinert). Note: during the Screening/Run-In period, C1-INH may be used to treat an acute HAE attack. 3. Concurrent diagnosis of any other type of recurrent angioedema, including acquired or idiopathic angioedema. 4. Subjects who have known hypersensitivity to any lipid nanoparticles (LNP) component (or its excipients) or who have previously received LNP and experienced any treatment-related clinically significant laboratory abnormalities or AEs listed below: a. ALT or AST > 3 × ULN if baseline was normal or > 3 × baseline if baseline was above normal. b. INR, aPTT or d-dimer > 1.5 × ULN if baseline was normal or > 1.5 × baseline if baseline was above normal. c. Any LNP treatment-related AEs classified as CTCAE Grade 3 or higher. d. Infusion-related reaction (IRR) to an LNP-containing product (or excipients) requiring treatment or discontinuation of infusion; NOTE: slowing of the infusion rate to mitigate an IRR is not considered exclusionary. e. Any LNP treatment-related AEs which in the opinion of the Investigator should be exclusionary. 5. Exposure to angiotensin-converting enzyme (ACE) inhibitors or any estrogen-containing medications with systemic absorption within 90 days prior to study drug administration. 6. Unable or unwilling to take the required pre-treatment medication regimen. 7. Female subjects of childbearing potential are excluded from the study if they: a. are breastfeeding or plan to breastfeed during treatment and for an additional 12 months after the last study drug administration. b. have a positive pregnancy test at screening and/or Day 1. 8. Antithrombotic therapy other than aspirin (e.g., warfarin, dabigatran, apixaban) within 14 days prior to study drug administration. 9. History of thrombophilia, or positive genetic test for Factor V Leiden and/or prothrombin 20210. 10. History of cirrhosis. 11. Known or suspected systemic viral, parasitic, or fungal infection including coronavirus disease (COVID-19) or received antibiotics for bacterial infection within 14 days prior to Screening. 12. History of Hepatitis B or C infection or positive Hepatitis B surface antigen (HbsAg) or Hepatitis C virus antibody (HCVAb) test at Screening. 13. History of positive human immunodeficiency virus (HIV) status. 14. Prior liver, heart, or other solid organ transplant or bone marrow transplant or anticipated transplant within 1 year of Screening. Note: prior history of or planned corneal transplant is not exclusionary. 15. Subject has a history of alcohol or drug abuse within 3 years prior to Screening. 16. Any condition, laboratory abnormality, psycho-social stressor, pattern of behavior, or other reason that, in the Investigator's opinion, could adversely affect t
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase 1 • Safety and tolerability as determined by adverse events (AEs) • Dose-limiting toxicities (DLTs) • Phase 2 • Number of HAE attacks per month (by HAE Attack Assessment and Reporting Procedure and Reporting Procedure - see Section 10.3), Weeks 1 to 16 | — |
Secondary
| Measure | Time frame |
|---|---|
| Phase 1 Secondary • Change from baseline in total plasma prekallikrein/kallikrein protein level. • Plasma and urine concentrations for DMG-PEG2k, LP000001, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) messenger ribonucleic acid (mRNA), and single guide RNA (sgRNA). Phase 1 Exploratory • Number of HAE attacks per month (by HAE Attack Assessment and Reporting Procedure - see Section 10.3) and number of HAE attacks requiring acute therapy per month (Weeks 1 to 16, Weeks 5 to 16) • Incidence and titer of anti-drug antibodies (ADA) to NTLA-2002 and anti-Cas9 protein antibodies. • Change from baseline in plasma kallikrein activity Phase 2 Secondary • Safety and tolerability as determined by adverse events (AEs). • Number of HAE attacks per month (by HAE Attack Assessment and Reporting Procedure - see Section 10.3) (Weeks 5 to 16) and number of HAE attacks requiring acute therapy per month (Weeks 1 to 16, Weeks 5 to 16) • Number of moderate or severe HAE attacks per month (Weeks 5 to 16) • Change from baseline in total plasma prekallikrein/kallikrein protein level. • Plasma and urine concentrations for DMG-PEG2k, LP000001, Cas9 mRNA, and sgRNA Phase 2 Exploratory • Incidence and titer of ADA to NTLA-2002 and anti-Cas9 protein antibodies • Change from baseline in utilization of on-demand HAE medications for attacks (Weeks 1 to 16, Weeks 5 to 16) • Change from baseline in healthcare utilization for HAE attacks (Weeks 1 to 16, Weeks 5 to 16) • Change from baseline in quality of life (QoL) parameters as measured by MOXIE Angioedema QoL instrument, EQ-5D-5L, and WPAI-GH. • Change from baseline in plasma kallikrein activity | — |
Countries
Netherlands
Outcome results
None listed