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This study will be conducted to evaluate the safety, tolerability, activity, pharmacokinetics, and pharmacodynamics of NTLA-2002 in adults with Hereditary Angioedema (HAE).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Phase 1 Study Arm | Experimental | 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. |
|
| Phase 2 Experimental Study Arm | Experimental | 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. |
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| Phase 2 Placebo Comparator Study Arm | Placebo Comparator | 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. |
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| Placebo Crossover and Follow-On Dosing Substudy Arm | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Biological NTLA-2002 | Biological | CRISPR/Cas9 gene editing system delivered by LNP for IV administration |
|
| Measure | Description | Time Frame |
|---|---|---|
| Safety and tolerability of NTLA-2002 as determined by adverse events (AEs) and dose limiting toxicities (DLTs) | (Phase 1 only) | From NTLA-2002 infusion up to week 104 post-infusion |
| Number of HAE attacks per month (Weeks 1-16) | (Phase 2 only) | From study drug infusion up to week 16 post-infusion |
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline in total plasma kallikrein protein level | (Phase 1 & 2) | From NTLA-2002 infusion up to week 104 post-infusion |
| Plasma and urine concentrations for DMG-PEG2k, LP000001, Cas9 mRNA, and sgRNA |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Trial Site | Campbelltown | Australia | ||||
| Clinical Trial Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39445704 | Derived | Cohn DM, Gurugama P, Magerl M, Katelaris CH, Launay D, Bouillet L, Petersen RS, Lindsay K, Aygoren-Pursun E, Maag D, Butler JS, Shah MY, Golden A, Xu Y, Abdelhady AM, Lebwohl D, Longhurst HJ. CRISPR-Based Therapy for Hereditary Angioedema. N Engl J Med. 2025 Jan 30;392(5):458-467. doi: 10.1056/NEJMoa2405734. Epub 2024 Oct 24. | |
| 38294975 |
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| ID | Term |
|---|---|
| D054179 | Angioedemas, Hereditary |
| ID | Term |
|---|---|
| D000799 | Angioedema |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D000081208 | Hereditary Complement Deficiency Diseases |
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Phase 1 is an open label non-randomized study Phase 2 is a randomized, double-blind, placebo-controlled study
| Normal Saline IV Administration | Other | The administration of IV normal saline |
|
(Phase 1 & 2)
| From NTLA-2002 infusion up to week 104 post-infusion |
| Safety and tolerability of NTLA-2002 as determined by AEs | (Phase 2 only) | From study drug infusion up to week 104 post-infusion |
| Number of HAE attacks per month (Weeks 5-16) | (Phase 2 only) | From week 6 post-infusion up to week 16 post-infusion |
| Number of HAE attacks per month requiring acute therapy (Weeks 1-16, Weeks 5-16) | (Phase 2 only) | From study drug infusion up to week 16 post-infusion |
| Grenoble |
| France |
| Clinical Trial Site | Lille | France |
| Clinical Trial Site | Paris | France |
| Clinical Trial Site | Berlin | Germany |
| Clinical Trial Site | Frankfurt | Germany |
| Clinical Trial Site | Amsterdam | Netherlands |
| Clinical Trial Site | Auckland | New Zealand |
| Clinical Trial Site | Cambridge | United Kingdom |
| Longhurst HJ, Lindsay K, Petersen RS, Fijen LM, Gurugama P, Maag D, Butler JS, Shah MY, Golden A, Xu Y, Boiselle C, Vogel JD, Abdelhady AM, Maitland ML, McKee MD, Seitzer J, Han BW, Soukamneuth S, Leonard J, Sepp-Lorenzino L, Clark ED, Lebwohl D, Cohn DM. CRISPR-Cas9 In Vivo Gene Editing of KLKB1 for Hereditary Angioedema. N Engl J Med. 2024 Feb 1;390(5):432-441. doi: 10.1056/NEJMoa2309149. |
| D000081207 | Primary Immunodeficiency Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D014581 | Urticaria |
| D017445 | Skin Diseases, Vascular |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D007153 | Immunologic Deficiency Syndromes |