Ignite Creation Date:
2025-12-24 @ 11:55 PM
Ignite Modification Date:
2025-12-25 @ 9:51 PM
Study NCT ID:
NCT04601051
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-05-01
First Post:
2020-10-19
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of NTLA-2001 in Patients With Hereditary Transthyretin Amyloidosis With Polyneuropathy (ATTRv-PN) and Patients With Transthyretin Amyloidosis-Related Cardiomyopathy (ATTR-CM)
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D028227', 'term': 'Amyloid Neuropathies, Familial'}, {'id': 'D011115', 'term': 'Polyneuropathies'}, {'id': 'D000686', 'term': 'Amyloidosis'}, {'id': 'D009202', 'term': 'Cardiomyopathies'}], 'ancestors': [{'id': 'D020271', 'term': 'Heredodegenerative Disorders, Nervous System'}, {'id': 'D019636', 'term': 'Neurodegenerative Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D017772', 'term': 'Amyloid Neuropathies'}, {'id': 'D010523', 'term': 'Peripheral Nervous System Diseases'}, {'id': 'D009468', 'term': 'Neuromuscular Diseases'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D028226', 'term': 'Amyloidosis, Familial'}, {'id': 'D008661', 'term': 'Metabolism, Inborn Errors'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D057165', 'term': 'Proteostasis Deficiencies'}, {'id': 'D006331', 'term': 'Heart Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C000718870', 'term': 'NTLA-2001'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SEQUENTIAL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 72}}, 'statusModule': {'overallStatus': 'ACTIVE_NOT_RECRUITING', 'startDateStruct': {'date': '2020-11-05', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-04', 'completionDateStruct': {'date': '2026-08', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-04-29', 'studyFirstSubmitDate': '2020-10-19', 'studyFirstSubmitQcDate': '2020-10-19', 'lastUpdatePostDateStruct': {'date': '2025-05-01', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2020-10-23', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2025-08', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Number of Participants with Treatment-Emergent Adverse Events', 'timeFrame': 'up to Day 730'}, {'measure': 'Number of Participants with Clinically Significant Clinical Laboratory Test Findings', 'timeFrame': 'up to Day 730'}, {'measure': 'Number of Participants with Clinically Significant Safety Measurements', 'timeFrame': 'up to Day 730'}, {'measure': 'Percent Change from Baseline in Serum TTR (enzyme-linked immunosorbent assay [ELISA])', 'timeFrame': 'up to Day 730'}, {'measure': 'Percent Change from Baseline in Serum Prealbumin', 'timeFrame': 'up to Day 730'}, {'measure': 'Mean Area Under the Plasma Concentration-Time Curve from Time Zero to the Time of the Last Measurable Concentration (AUClast) for DMG-PEG2k, LP000001, Cas9 mRNA, and sgRNA', 'timeFrame': 'up to Day 730'}, {'measure': 'Mean Area Under the Plasma Concentration-Time Curve from Time Zero to Infinity (AUCinf) for DMG-PEG2k, LP000001, Cas9 mRNA, and sgRNA', 'timeFrame': 'up to Day 730'}, {'measure': 'Mean Maximum Concentration (Cmax) for DMG-PEG2k, LP000001, Cas9 mRNA, and sgRNA', 'timeFrame': 'up to Day 730'}, {'measure': 'Mean Time of the Maximum Concentration (Tmax) for DMG-PEG2k, LP000001, Cas9 mRNA, and sgRNA', 'timeFrame': 'up to Day 730'}, {'measure': 'Mean Terminal Half-Life (t½) for DMG-PEG2k, LP000001, Cas9 mRNA, and sgRNA', 'timeFrame': 'up to Day 730'}, {'measure': 'Mean Apparent Clearance (CL) for DMG-PEG2k, LP000001, Cas9 mRNA, and sgRNA', 'timeFrame': 'up to Day 730'}, {'measure': 'Mean Volume of Distribution (Vd) for DMG-PEG2k, LP000001, Cas9 mRNA, and sgRNA', 'timeFrame': 'up to Day 730'}, {'measure': 'Change from Baseline in Anti-Drug Antibody to NTLA-2001 and Anti-Cas9 Protein Antibody to Transgene Product Levels', 'timeFrame': 'up to Day 730'}], 'secondaryOutcomes': [{'measure': 'Polyneuropathy only: Change from Baseline in Familial Amyloid Polyneuropathy (FAP) Stage.', 'timeFrame': 'up to Day 730'}, {'measure': 'Polyneuropathy only: Change from Baseline in Polyneuropathy Disability (PND) Score', 'timeFrame': 'up to Day 730'}, {'measure': 'Polyneuropathy only: Change from Baseline in Modified Body Mass Index (mBMI)', 'timeFrame': 'up to Day 730'}, {'measure': 'Polyneuropathy only: Change from Screening in Neuropathy Impairment Score (NIS)', 'timeFrame': 'up to Day 730'}, {'measure': 'Polyneuropathy only: Change from Baseline in Modified Neuropathy Impairment Score +7 (mNIS+7)', 'timeFrame': 'up to Day 730'}, {'measure': 'Polyneuropathy only: Change from Screening in 10-Meter Walk Test (10-MWT)', 'timeFrame': 'up to Day 730'}, {'measure': 'Polyneuropathy only: Change from Baseline in Norfolk Quality of Life-Diabetic Neuropathy (QOL-DN)', 'timeFrame': 'up to Day 730'}, {'measure': 'Polyneuropathy only: Change from Baseline in EuroQOL (EQ)-5D-5L', 'timeFrame': 'up to Day 730'}, {'measure': 'Cardiomyopathy only: Change from Baseline in N-terminal prohormone of brain natriuretic peptide (NT-proBNP)', 'timeFrame': 'up to Day 730'}, {'measure': 'Cardiomyopathy only: Change from Baseline in hs Troponin T', 'timeFrame': 'up to Day 730'}, {'measure': 'Cardiomyopathy only: Change from Baseline in Magnetic resonance imaging (MRI)', 'timeFrame': 'up to Day 730'}, {'measure': 'Cardiomyopathy only: Change from Baseline in Echocardiogram', 'timeFrame': 'up to Day 730'}, {'measure': 'Cardiomyopathy only: Change from Baseline in Cardio-pulmonary exercise test', 'timeFrame': 'up to Day 730'}, {'measure': 'Cardiomyopathy only: Change from Baseline in 6-Minute Walk Test (6-MWT)', 'timeFrame': 'up to Day 730'}, {'measure': 'Cardiomyopathy only: Change from Baseline in New York Heart Association (NYHA) Classification', 'timeFrame': 'up to Day 730'}, {'measure': 'Cardiomyopathy only: Change from Baseline in Patient-reported outcomes (KCCQ)', 'timeFrame': 'up to Day 730'}]}, 'oversightModule': {'isUsExport': True, 'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['NTLA-2001', 'Pharmacokinetics', 'Pharmacodynamics', 'Neurologic Function', 'Clustered Regularly Interspaced Short Palindromic Repeats', 'CRISPR', 'Polyneuropathy', 'ATTR', 'Transthyretin', 'TTR', 'Amyloidosis', 'Familial Amyloid Polyneuropathy', 'FAP', 'Cardiomyopathy'], 'conditions': ['Transthyretin-Related (ATTR) Familial Amyloid Polyneuropathy', 'Transthyretin-Related (ATTR) Familial Amyloid Cardiomyopathy', 'Wild-Type Transthyretin Cardiac Amyloidosis']}, 'referencesModule': {'references': [{'pmid': '41002250', 'type': 'DERIVED', 'citation': 'Gillmore JD, Gane E, Taubel J, Pilebro B, Echaniz-Laguna A, Kao J, Litchy W, Shahda S, Haagensen A, Walsh L, Smith D, Kachadourian J, Ward JH, Lebwohl D, Zhu P, Xu Y, Leung A, Sonderfan A, Gutstein DE, Manvelian G, Adams D. Nexiguran Ziclumeran Gene Editing in Hereditary ATTR with Polyneuropathy. N Engl J Med. 2025 Oct 9;393(14):1375-1386. doi: 10.1056/NEJMoa2510209. Epub 2025 Sep 25.'}, {'pmid': '39555828', 'type': 'DERIVED', 'citation': 'Fontana M, Solomon SD, Kachadourian J, Walsh L, Rocha R, Lebwohl D, Smith D, Taubel J, Gane EJ, Pilebro B, Adams D, Razvi Y, Olbertz J, Haagensen A, Zhu P, Xu Y, Leung A, Sonderfan A, Gutstein DE, Gillmore JD. CRISPR-Cas9 Gene Editing with Nexiguran Ziclumeran for ATTR Cardiomyopathy. N Engl J Med. 2024 Dec 12;391(23):2231-2241. doi: 10.1056/NEJMoa2412309. Epub 2024 Nov 16.'}, {'pmid': '34215024', 'type': 'DERIVED', 'citation': "Gillmore JD, Gane E, Taubel J, Kao J, Fontana M, Maitland ML, Seitzer J, O'Connell D, Walsh KR, Wood K, Phillips J, Xu Y, Amaral A, Boyd AP, Cehelsky JE, McKee MD, Schiermeier A, Harari O, Murphy A, Kyratsous CA, Zambrowicz B, Soltys R, Gutstein DE, Leonard J, Sepp-Lorenzino L, Lebwohl D. CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis. N Engl J Med. 2021 Aug 5;385(6):493-502. doi: 10.1056/NEJMoa2107454. Epub 2021 Jun 26."}, {'pmid': '34175043', 'type': 'DERIVED', 'citation': 'Stephenson AA, Flanigan KM. Gene editing and modulation for Duchenne muscular dystrophy. Prog Mol Biol Transl Sci. 2021;182:225-255. doi: 10.1016/bs.pmbts.2021.01.029. Epub 2021 Mar 3.'}]}, 'descriptionModule': {'briefSummary': 'This study will be conducted to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of NTLA-2001 in participants with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) and participants with hereditary transthyretin amyloidosis with cardiomyopathy (ATTRv-CM) or wild type cardiomyopathy (ATTRwt-CM)', 'detailedDescription': 'For ATTRv-PN participants, Part 1 consists of an open-label, single-ascending dose study, which identifies the dose for evaluation in the cohort expansion of Part 2. Part 2 will follow as an open-label, dose expansion study to further characterize the activity of NTLA-2001, provide an initial assessment of the effect of NTLA-2001 on clinical measures of neuropathy and neurological function, and obtain additional safety data.\n\nFor ATTR-CM participants, Part 1 consists of an open-label, single-ascending dose study, which identifies the dose for evaluation in the cohort expansion of Part 2. Part 2 will follow as an open-label, dose expansion study to further characterize the activity of NTLA-2001, provide an initial assessment of the effect of NTLA-2001 on cardiac measures, and obtain additional safety data.\n\nAll participants who are dosed with NTLA-2001 will be offered to participate in a long-term safety monitoring follow-up study via a separate protocol.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '90 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Polyneuropathy Inclusion Criteria:\n\n* Male and/or female participants 18 to 80 years of age inclusive, at the time of signing the informed consent\n* Diagnosis of polyneuropathy (PN) due to transthyretin (TTR) amyloidosis (ATTR)\n* Must have a body weight of at least 45 kilograms (kg) at Screening visit\n* Lack of access to approved treatments for ATTR and/or progression of hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) despite use of approved treatment for ATTRv-PN\n\nPolyneuropathy Exclusion Criteria:\n\n* Amyloidosis attributable to non-TTR protein, e.g., amyloid light-chain (AL) amyloidosis\n* Known leptomeningeal transthyretin amyloidosis\n* Use of any of the following TTR-directed therapy for ATTR within certain timeframe:\n\n 1. Patisiran\n 2. Inotersen\n 3. Vutrisiran\n 4. Tafamidis\n 5. Diflunisal\n 6. Doxycycline and/or tauroursodeoxycholic acid\n 7. Any other investigational agent for the treatment of ATTRv-PN:\n* Other protocol defined Inclusion/Exclusion criteria may apply\n\nCardiomyopathy Inclusion Criteria (UK only):\n\n* Male and/or female participants 18 to 90 years of age inclusive, at the time of signing the informed consent\n* Diagnosis of transthyretin (ATTR) amyloidosis with cardiomyopathy, classified as hereditary ATTR amyloidosis with cardiomyopathy (ATTRv-CM) or wild type cardiomyopathy (ATTRwt-CM).\n* Must have a body weight of at least 45 kilograms (kg) at Screening visit\n* New York Heart Association (NYHA) Class I-III heart failure\n* At least 1 prior hospitalization for heart failure and/or clinical evidence of heart failure.\n* Able to complete ≥150 meters on the 6-minute walk test (6-MWT) during the Screening period.\n\nCardiomyopathy Exclusion Criteria (UK only):\n\n* Amyloidosis attributable to non-TTR protein, e.g., amyloid light-chain (AL) amyloidosis\n* Known leptomeningeal transthyretin amyloidosis\n* Use of any of the following TTR-directed therapy for ATTR within certain timeframes:\n\n 1. Patisiran\n 2. Inotersen\n 3. Vutrisiran\n 4. Tafamidis\n 5. Diflunisal\n 6. Doxycycline and/or tauroursodeoxycholic acid\n 7. Investigational TTR stabilizer (e.g., AG-10)\n* Participants with heart failure that in the opinion of the investigator is caused by ischemic heart disease, hypertension, or uncorrected valvular disease and not primarily due to transthyretin amyloid cardiomyopathy.\n* Participants with a history of sustained ventricular tachycardia or aborted ventricular fibrillation or with a history of atrioventricular (AV) nodal or sinoatrial (SA) nodal dysfunction for which a pacemaker is indicated but will not be placed. Pacemaker or defibrillator placement, initiation of or change in anti-arrhythmic medication within 28 days prior to study drug administration.\n* Other protocol defined Inclusion/Exclusion criteria may apply'}, 'identificationModule': {'nctId': 'NCT04601051', 'briefTitle': 'Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of NTLA-2001 in Patients With Hereditary Transthyretin Amyloidosis With Polyneuropathy (ATTRv-PN) and Patients With Transthyretin Amyloidosis-Related Cardiomyopathy (ATTR-CM)', 'organization': {'class': 'INDUSTRY', 'fullName': 'Intellia Therapeutics'}, 'officialTitle': 'Phase 1 Two-Part (Open-label, Single Ascending Dose (Part 1) and Open-label, Single Dose Expansion (Part 2)) Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of NTLA-2001 in Patients With Hereditary Transthyretin Amyloidosis With Polyneuropathy (ATTRv-PN) and Patients With Transthyretin Amyloidosis-Related Cardiomyopathy (ATTR-CM)', 'orgStudyIdInfo': {'id': 'ITL-2001-CL-001'}, 'secondaryIdInfos': [{'id': '2020-002034-32', 'type': 'EUDRACT_NUMBER'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Polyneuropathy Part 1: NTLA-2001', 'description': 'Participants, assigned to one of 4 dose-escalation cohorts, will receive a single dose of NTLA-2001.', 'interventionNames': ['Biological: NTLA-2001']}, {'type': 'EXPERIMENTAL', 'label': 'Polyneuropathy Part 2: NTLA-2001', 'description': 'Participants, assigned to the dose-expansion cohort, will receive a single dose of NTLA-2001.', 'interventionNames': ['Biological: NTLA-2001']}, {'type': 'EXPERIMENTAL', 'label': 'Cardiomyopathy Part 1 (UK only): NTLA-2001', 'description': 'Participants, assigned to one of 2 dose-escalation cohorts, will receive a single dose of NTLA-2001.', 'interventionNames': ['Biological: NTLA-2001']}, {'type': 'EXPERIMENTAL', 'label': 'Cardiomyopathy Part 2 (UK only): NTLA-2001', 'description': 'Participants, assigned to the dose-expansion cohort, will receive a single dose of NTLA-2001.', 'interventionNames': ['Biological: NTLA-2001']}, {'type': 'EXPERIMENTAL', 'label': 'Polyneuropathy Follow-on Dosing (PN Part 1 Dose Level 1 Subjects only): NTLA-2001', 'description': 'Participants assigned to the follow-on dosing cohort will receive a subsequent dose of NTLA-2001.', 'interventionNames': ['Biological: NTLA-2001']}], 'interventions': [{'name': 'NTLA-2001', 'type': 'BIOLOGICAL', 'description': 'A clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing system delivered by lipid nanoparticles (LNPs) for intravenous (IV) administration', 'armGroupLabels': ['Cardiomyopathy Part 1 (UK only): NTLA-2001', 'Cardiomyopathy Part 2 (UK only): NTLA-2001', 'Polyneuropathy Follow-on Dosing (PN Part 1 Dose Level 1 Subjects only): NTLA-2001', 'Polyneuropathy Part 1: NTLA-2001', 'Polyneuropathy Part 2: NTLA-2001']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Paris', 'country': 'France', 'facility': 'Clinical Trial Site', 'geoPoint': {'lat': 48.85341, 'lon': 2.3488}}, {'city': 'Auckland', 'country': 'New Zealand', 'facility': 'Clinical Trial Site', 'geoPoint': {'lat': -36.84853, 'lon': 174.76349}}, {'city': 'Umeå', 'country': 'Sweden', 'facility': 'Clinical Trial Site', 'geoPoint': {'lat': 63.82842, 'lon': 20.25972}}, {'city': 'London', 'country': 'United Kingdom', 'facility': 'Clinical Trial Site', 'geoPoint': {'lat': 51.50853, 'lon': -0.12574}}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Intellia Therapeutics', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}