Ignite Creation Date:
2025-12-24 @ 11:39 PM
Ignite Modification Date:
2026-01-01 @ 1:41 PM
Study NCT ID:
NCT03757351
Status:
TERMINATED
Last Update Posted:
2025-09-22
First Post:
2018-11-27
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Study to Evaluate DNL747 in Subjects With Amyotrophic Lateral Sclerosis
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D000690', 'term': 'Amyotrophic Lateral Sclerosis'}], 'ancestors': [{'id': 'D013118', 'term': 'Spinal Cord Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D016472', 'term': 'Motor Neuron Disease'}, {'id': 'D019636', 'term': 'Neurodegenerative Diseases'}, {'id': 'D057177', 'term': 'TDP-43 Proteinopathies'}, {'id': 'D009468', 'term': 'Neuromuscular Diseases'}, {'id': 'D057165', 'term': 'Proteostasis Deficiencies'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'DOUBLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'CROSSOVER'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 15}}, 'statusModule': {'whyStopped': "Due to change in Sanofi's development strategy for DNL747/SAR443060 - not due to any safety concerns", 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2018-12-14', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-09', 'completionDateStruct': {'date': '2020-06-18', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2025-09-17', 'studyFirstSubmitDate': '2018-11-27', 'studyFirstSubmitQcDate': '2018-11-27', 'lastUpdatePostDateStruct': {'date': '2025-09-22', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2018-11-28', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2020-06-18', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Number of Subjects with Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)', 'timeFrame': 'Randomization - Day 86'}, {'measure': 'Number of Subjects with clinically significant neurological examination abnormalities', 'timeFrame': 'Randomization - Day 86'}, {'measure': 'Number of Subjects with laboratory test abnormalities', 'timeFrame': 'Randomization - Day 86'}], 'secondaryOutcomes': [{'measure': 'Pharmacokinetic measure of maximum observed plasma concentration (Cmax) of DNL747', 'timeFrame': 'Randomization - Day 86'}, {'measure': 'Pharmacokinetic measure of time to reach maximum observed plasma concentration (Tmax) of DNL747', 'timeFrame': 'Randomization - Day 86'}, {'measure': 'Pharmacokinetic measure of area under the plasma drug concentration-time curve (AUC) of DNL747', 'timeFrame': 'Randomization - Day 86'}, {'measure': 'Pharmacokinetic terminal disposition rate constant (λz) with the respective t1/2 of DNL747', 'timeFrame': 'Randomization - Day 86'}, {'measure': 'Pharmacokinetic measure of CSF concentrations of DNL747', 'timeFrame': 'Randomization - Day 86'}, {'measure': 'Pharmacodynamic measure of pS166 in PBMCs', 'timeFrame': 'Randomization - Day 86'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Amyotrophic Lateral Sclerosis']}, 'referencesModule': {'references': [{'pmid': '35649245', 'type': 'DERIVED', 'citation': 'Vissers MFJM, Heuberger JAAC, Groeneveld GJ, Oude Nijhuis J, De Deyn PP, Hadi S, Harris J, Tsai RM, Cruz-Herranz A, Huang F, Tong V, Erickson R, Zhu Y, Scearce-Levie K, Hsiao-Nakamoto J, Tang X, Chang M, Fox BM, Estrada AA, Pomponio RJ, Alonso-Alonso M, Zilberstein M, Atassi N, Troyer MD, Ho C. Safety, pharmacokinetics and target engagement of novel RIPK1 inhibitor SAR443060 (DNL747) for neurodegenerative disorders: Randomized, placebo-controlled, double-blind phase I/Ib studies in healthy subjects and patients. Clin Transl Sci. 2022 Aug;15(8):2010-2023. doi: 10.1111/cts.13317. Epub 2022 Jun 1.'}], 'seeAlsoLinks': [{'url': 'https://www.trialsummaries.com/Study/StudyDetails?id=25354&tenant=MT_SNY_9011', 'label': 'TDR16536 Plain Language Results Summary'}]}, 'descriptionModule': {'briefSummary': 'The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple oral doses of DNL747 in subjects with Amyotrophic Lateral Sclerosis in a cross-over design'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '80 Years', 'minimumAge': '21 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Key Inclusion Criteria (Double-Blind Part):\n\n* Women of non-childbearing potential and men, aged 21-80 years\n* Willingness and ability to complete all aspects of the study; participant should be capable of completing assessments either alone or with help of a caregiver\n* Diagnosis of laboratory-supported probable, probable, or definite (sporadic or familial) ALS according to the El Escorial World Federation of Neurology revised research diagnostic criteria\n* Less than 3 years since symptom onset\n* Forced vital capacity (FVC) \\>50% predicted measured within 30 days of screening\n* If subject is taking approved ALS treatments (riluzole and/or edaravone), doses must be stable for ≥2 months prior to screening and subject is expected to stay on a stable regimen throughout the study\n\nKey Exclusion Criteria (Double-Blind Part):\n\n* History of a clinically significant non-ALS neurologic disorder (other than frontal temporal lobe dementia), including, but not limited to, muscular dystrophy, spinal stenosis, peripheral neuropathy, inherited neuropathies, AD, Parkinson's disease, Lewy body dementia, vascular dementia, Huntington's disease, epilepsy, stroke, multiple sclerosis, brain tumor, or brain infection or abscess\n* Unstable or poorly controlled comorbid disease process of any organ system currently requiring active treatment or likely to require treatment adjustment during the study\n\nKey Inclusion Criteria (Open-Label Extension):\n\n* Successful completion of both periods of the the double-blind, crossover part of the study\n* Continued diagnosis of laboratory-supported probable, probable, or definite (sporadic or familial) ALS according to the El Escorial World Federation of Neurology revised research diagnostic criteria\n\nKey Exclusion Criteria (Open-Label Extension):\n\n* Presence of laboratory abnormalities, physical examination findings, or AEs determined to be clinically significant by the investigator from the double-blind part of the study that have not resolved by the final follow-up visit as part of the double-blind study period\n* New diagnosis of clinically significant neurological disorder (other than frontal temporal lobe dementia)"}, 'identificationModule': {'nctId': 'NCT03757351', 'briefTitle': 'Study to Evaluate DNL747 in Subjects With Amyotrophic Lateral Sclerosis', 'organization': {'class': 'INDUSTRY', 'fullName': 'Sanofi'}, 'officialTitle': 'A Multicenter, Randomized, Placebo-Controlled, Double-Blind, Phase 1b Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL747 in Subjects With Amyotrophic Lateral Sclerosis', 'orgStudyIdInfo': {'id': 'TDR16536'}, 'secondaryIdInfos': [{'id': 'DNLI-D-0003', 'type': 'OTHER', 'domain': 'Denali Therapeutics Inc.'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'DNL747 First, Placebo Second', 'interventionNames': ['Drug: DNL747', 'Drug: Placebo']}, {'type': 'EXPERIMENTAL', 'label': 'Placebo First, DNL747 Second', 'interventionNames': ['Drug: DNL747', 'Drug: Placebo']}, {'type': 'EXPERIMENTAL', 'label': 'Open-Label Extension', 'description': 'Conducted in the Netherlands only.', 'interventionNames': ['Drug: DNL747']}], 'interventions': [{'name': 'DNL747', 'type': 'DRUG', 'description': 'Repeating oral dose', 'armGroupLabels': ['DNL747 First, Placebo Second', 'Open-Label Extension', 'Placebo First, DNL747 Second']}, {'name': 'Placebo', 'type': 'DRUG', 'description': 'Repeating oral dose', 'armGroupLabels': ['DNL747 First, Placebo Second', 'Placebo First, DNL747 Second']}]}, 'contactsLocationsModule': {'locations': [{'zip': '32806', 'city': 'Orlando', 'state': 'Florida', 'country': 'United States', 'facility': 'Bioclinica', 'geoPoint': {'lat': 28.53834, 'lon': -81.37924}}, {'zip': '84124', 'city': 'Salt Lake City', 'state': 'Utah', 'country': 'United States', 'facility': 'PRA Health Sciences', 'geoPoint': {'lat': 40.76078, 'lon': -111.89105}}, {'zip': '2333', 'city': 'Leiden', 'state': 'South Holland', 'country': 'Netherlands', 'facility': 'CHDR', 'geoPoint': {'lat': 52.15833, 'lon': 4.49306}}], 'overallOfficials': [{'name': 'Clinical Sciences & Operations', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Sanofi'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'YES', 'description': "Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org"}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Sanofi', 'class': 'INDUSTRY'}, 'collaborators': [{'name': 'Denali Therapeutics Inc.', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'SPONSOR'}}}}