Ignite Creation Date:
2025-12-24 @ 4:46 PM
Ignite Modification Date:
2025-12-26 @ 10:29 PM
Study NCT ID:
NCT02709850
Status:
COMPLETED
Last Update Posted:
2020-11-19
First Post:
2015-11-22
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IONIS ANGPTL3-LRx in Healthy Volunteers With Elevated Triglycerides and Participants With Familial Hypercholesterolemia
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D015228', 'term': 'Hypertriglyceridemia'}, {'id': 'D006938', 'term': 'Hyperlipoproteinemia Type II'}], 'ancestors': [{'id': 'D006949', 'term': 'Hyperlipidemias'}, {'id': 'D050171', 'term': 'Dyslipidemias'}, {'id': 'D052439', 'term': 'Lipid Metabolism Disorders'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D008052', 'term': 'Lipid Metabolism, Inborn Errors'}, {'id': 'D008661', 'term': 'Metabolism, Inborn Errors'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D006951', 'term': 'Hyperlipoproteinemias'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C000621591', 'term': 'IONIS-ANGPTL3-LRx'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'DOUBLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR']}, 'primaryPurpose': 'OTHER', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 48}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2015-11-30', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2020-11', 'completionDateStruct': {'date': '2017-06-26', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2020-11-17', 'studyFirstSubmitDate': '2015-11-22', 'studyFirstSubmitQcDate': '2016-03-10', 'lastUpdatePostDateStruct': {'date': '2020-11-19', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2016-03-16', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2017-04-12', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Safety and tolerability of single and multiple doses of IONIS ANGPTL3-LRx (incidence, severity, and dose-relationship of adverse effects and changes in the laboratory parameters)', 'timeFrame': 'Up to Day 127', 'description': 'The safety and tolerability of IONIS ANGPTL3-LRx will be assessed by determining the incidence, severity, and dose-relationship of adverse effects and changes in the laboratory parameters by dose. Safety results in subjects dosed with IONIS ANGPTL3-LRx will be compared with those from subjects dosed with placebo.'}, {'measure': 'Pharmacokinetics after single and multiple doses of IONIS ANGPTL3-LRx.', 'timeFrame': 'Up to Day 127', 'description': 'The plasma pharmacokinetics (concentration-time results) of IONIS ANGPTL3-LRx (unconjugated and conjugated ASO) will be assessed following single and multiple-dose SC administration. The amount of IONIS ANGPTL3-LRx excreted in urine at selected 24-hour intervals will also be determined.'}, {'measure': 'Pharmacodynamics of IONIS ANGPTL3-LRx (Changes in serum ANGPTL3 levels)', 'timeFrame': 'Up to Day 127', 'description': 'Changes in serum angiopoietin-like 3 (ANGPTL3) levels compared to baseline.'}], 'secondaryOutcomes': [{'measure': 'Pharmacodynamic effects of IONIS ANGPTL3-LRx', 'timeFrame': 'Up to Day 127', 'description': 'Effects of IONIS ANGPTL3-LRx on changes in ANGPTL3 plasma protein compared to baseline.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['ANGPTL-3'], 'conditions': ['Hypertriglyceridemia', 'Familial Hypercholesterolemia']}, 'referencesModule': {'references': [{'pmid': '28538111', 'type': 'DERIVED', 'citation': 'Graham MJ, Lee RG, Brandt TA, Tai LJ, Fu W, Peralta R, Yu R, Hurh E, Paz E, McEvoy BW, Baker BF, Pham NC, Digenio A, Hughes SG, Geary RS, Witztum JL, Crooke RM, Tsimikas S. Cardiovascular and Metabolic Effects of ANGPTL3 Antisense Oligonucleotides. N Engl J Med. 2017 Jul 20;377(3):222-232. doi: 10.1056/NEJMoa1701329. Epub 2017 May 24.'}]}, 'descriptionModule': {'briefSummary': 'The purpose is to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of IONIS ANGPTL3-LRx (ISIS 703802) given to healthy volunteer subjects with elevated triglycerides and subjects with familial hypercholesterolemia.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '65 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria for All Cohorts:\n\n* Must have given written informed consent and be able to comply with all study requirements\n* Males or females 18 to 65 years, inclusive, at the time of informed consent\n* Body Mass Index (BMI) ≤ 35.0 kg/m2\n* Females must be non-pregnant and non-lactating, and either surgically sterile or postmenopausal.\n* Males must be surgically sterile, abstinent or using an acceptable contraceptive method\n\nInclusion criteria for Cohorts, A, D, and AA to DD only:\n\n* Fasting triglycerides (TG) ≥ 150 mg/dL at Screening\n* Fasting low density lipoprotein cholesterol (LDL-C) \\> 70 mg/dL at Screening\n\nInclusion criteria for Cohorts B and C only:\n\n* Fasting TG 90 - 150 mg/dL at Screening\n* Fasting LDL-C \\> 70 mg/dL at Screening\n\nInclusion Criteria for Cohort EE Only:\n\n* Homozygous FH diagnosis and fasting LDL-C ≥ 190 mg/dL (4.9 mmol/L)\n\nInclusion Criteria for Cohort FF Only:\n\n* Heterozygous FH diagnosis and fasting LDL-C ≥ 160 mg/dL (4.1 mmol/L)\n\nInclusion Criteria for Cohorts EE and FF Only:\n\n* Maximally tolerated stable LDL-C lowering agents (stable for at least 12 weeks)\n* On stable low-fat diet\n* Stable weight (± 4 kg) for ≥ 6 weeks prior to screening\n\nExclusion Criteria for All Cohorts:\n\n* Known history or positive test for Human Immunodeficiency Virus (HIV), Hepatitis C (HCV), or Hepatitis B (HBV)\n* Treatment with another Study Drug, biological agent, or device within one-month or 5-half-lives of screening\n* Regular use of alcohol within 6 months of screening\n* Use of concomitant drugs unless authorized by the Sponsor Medical Monitor\n* Known contraindication and/or allergy to heparin\n* Smoking \\> 10 cigarettes a day\n* Considered unsuitable for inclusion by the Principal Investigator\n\nExclusion Criteria for Cohorts EE and FF:\n\n* Myocardial infarction, percutaneous transluminal coronary intervention, or coronary artery bypass graft surgery within 12 weeks prior to screening, or cerebrovascular accident within 24 weeks prior to screening. Participants with adequately treated stable angina, per Investigator assessment, may be included\n* Congestive heart failure defined by NYHA Classes III or IV\n* Type 2 diabetes mellitus (T2DM) with HbA1c \\> 8.0%\n* Prior treatment with gene therapy\n* Currently receiving apheresis treatments or last apheresis treatment was within 8 weeks of screening'}, 'identificationModule': {'nctId': 'NCT02709850', 'briefTitle': 'Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IONIS ANGPTL3-LRx in Healthy Volunteers With Elevated Triglycerides and Participants With Familial Hypercholesterolemia', 'organization': {'class': 'INDUSTRY', 'fullName': 'Ionis Pharmaceuticals, Inc.'}, 'officialTitle': 'A Placebo-Controlled, Dose-Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Doses of ISIS 703802, Targeting ANGPTL3, Administered Subcutaneously to Healthy Volunteers With Elevated Triglycerides and Subjects With Familial Hypercholesterolemia', 'orgStudyIdInfo': {'id': 'ISIS 703802-CS1'}, 'secondaryIdInfos': [{'id': '2015-004003-23', 'type': 'EUDRACT_NUMBER'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'PLACEBO_COMPARATOR', 'label': 'Cohorts A, D: Placebo', 'description': 'Participants received a single-dose of IONIS ANGPTL3-LRx-matching placebo subcutaneously on Day 1.', 'interventionNames': ['Drug: Placebo']}, {'type': 'EXPERIMENTAL', 'label': 'Cohorts A, D: IONIS ANGPTL3-LRx 20 mg', 'description': 'Participants received a single-dose of IONIS ANGPTL3-LRx 20 milligrams (mg) subcutaneously on Day 1.', 'interventionNames': ['Drug: IONIS ANGPTL3-LRx']}, {'type': 'EXPERIMENTAL', 'label': 'Cohorts A, D: IONIS ANGPTL3-LRx 120 mg', 'description': 'Participants received a single-dose of IONIS ANGPTL3-LRx 120 mg subcutaneously on Day 1.', 'interventionNames': ['Drug: IONIS ANGPTL3-LRx']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Cohorts B, C: Placebo', 'description': 'Participants received a single-dose of IONIS ANGPTL3-LRx-matching placebo subcutaneously on Day 1.', 'interventionNames': ['Drug: Placebo']}, {'type': 'EXPERIMENTAL', 'label': 'Cohorts B, C: IONIS ANGPTL3-LRx 40 mg', 'description': 'Participants received a single-dose of IONIS ANGPTL3-LRx 40 mg subcutaneously on Day 1.', 'interventionNames': ['Drug: IONIS ANGPTL3-LRx']}, {'type': 'EXPERIMENTAL', 'label': 'Cohorts B, C: IONIS ANGPTL3-LRx 80 mg', 'description': 'Participants received a single-dose of IONIS ANGPTL3-LRx 80 mg subcutaneously on Day 1.', 'interventionNames': ['Drug: IONIS ANGPTL3-LRx']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Cohorts AA-DD: Placebo', 'description': 'Participants received IONIS ANGPTL3-LRx-matching placebo subcutaneously once per week for 6 weeks.', 'interventionNames': ['Drug: Placebo']}, {'type': 'EXPERIMENTAL', 'label': 'Cohorts AA-DD: IONIS ANGPTL3-LRx 10 mg', 'description': 'Participants received IONIS ANGPTL3-LRx 10 mg subcutaneously once per week for 6 weeks.', 'interventionNames': ['Drug: IONIS ANGPTL3-LRx']}, {'type': 'EXPERIMENTAL', 'label': 'Cohorts AA-DD: IONIS ANGPTL3-LRx 20 mg', 'description': 'Participants received IONIS ANGPTL3-LRx 20 mg subcutaneously once per week for 6 weeks.', 'interventionNames': ['Drug: IONIS ANGPTL3-LRx']}, {'type': 'EXPERIMENTAL', 'label': 'Cohorts AA-DD: IONIS ANGPTL3-LRx 40 mg', 'description': 'Participants received IONIS ANGPTL3-LRx 40 mg subcutaneously once per week for 6 weeks.', 'interventionNames': ['Drug: IONIS ANGPTL3-LRx']}, {'type': 'EXPERIMENTAL', 'label': 'Cohorts AA-DD: IONIS ANGPTL3-LRx 60 mg', 'description': 'Participants received IONIS ANGPTL3-LRx 60 mg subcutaneously once per week for 6 weeks.', 'interventionNames': ['Drug: IONIS ANGPTL3-LRx']}], 'interventions': [{'name': 'IONIS ANGPTL3-LRx', 'type': 'DRUG', 'otherNames': ['ISIS 703802'], 'armGroupLabels': ['Cohorts A, D: IONIS ANGPTL3-LRx 120 mg', 'Cohorts A, D: IONIS ANGPTL3-LRx 20 mg', 'Cohorts AA-DD: IONIS ANGPTL3-LRx 10 mg', 'Cohorts AA-DD: IONIS ANGPTL3-LRx 20 mg', 'Cohorts AA-DD: IONIS ANGPTL3-LRx 40 mg', 'Cohorts AA-DD: IONIS ANGPTL3-LRx 60 mg', 'Cohorts B, C: IONIS ANGPTL3-LRx 40 mg', 'Cohorts B, C: IONIS ANGPTL3-LRx 80 mg']}, {'name': 'Placebo', 'type': 'DRUG', 'description': '0.9%NaCl, water, riboflavin', 'armGroupLabels': ['Cohorts A, D: Placebo', 'Cohorts AA-DD: Placebo', 'Cohorts B, C: Placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': 'M9L 3A2', 'city': 'Toronto', 'state': 'Ontario', 'country': 'Canada', 'facility': 'Clinical Site', 'geoPoint': {'lat': 43.70643, 'lon': -79.39864}}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Ionis Pharmaceuticals, Inc.', 'class': 'INDUSTRY'}, 'collaborators': [{'name': 'Akcea Therapeutics', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'SPONSOR'}}}}