Ignite Creation Date:
2025-12-26 @ 10:37 AM
Ignite Modification Date:
2026-03-02 @ 6:43 PM
Study NCT ID:
NCT03647228
Status:
COMPLETED
Last Update Posted:
2021-02-04
First Post:
2018-08-23
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
A Phase 1/2a Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of IONIS-ENaCRx in Healthy Volunteers and Patients With Cystic Fibrosis
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D003550', 'term': 'Cystic Fibrosis'}], 'ancestors': [{'id': 'D010182', 'term': 'Pancreatic Diseases'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}, {'id': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D007232', 'term': 'Infant, Newborn, Diseases'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'DOUBLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 98}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2018-12-13', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2021-02', 'completionDateStruct': {'date': '2020-10-13', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2021-02-02', 'studyFirstSubmitDate': '2018-08-23', 'studyFirstSubmitQcDate': '2018-08-23', 'lastUpdatePostDateStruct': {'date': '2021-02-04', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2018-08-27', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2020-10-13', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Safety and Tolerability as Measured by the Number of Participants with at least one Treatment-Emergent Adverse Event', 'timeFrame': 'Up to 113 Days'}], 'secondaryOutcomes': [{'measure': 'Cmax: maximum observed drug concentration in plasma of IONIS-ENaCRx', 'timeFrame': 'Up to 113 Days'}, {'measure': 'Tmax: time taken to reach maximal concentration in plasma of IONIS-ENaCRx', 'timeFrame': 'Up to 113 Days'}, {'measure': 'AUCt: area under the plasma concentration-time curve from time zero to time t for IONIS-ENaCRx', 'timeFrame': 'Up to 113 Days'}, {'measure': 'CL/F: apparent total clearance of IONIS-ENaCRx', 'timeFrame': 'Up to 113 Days'}, {'measure': 't1/2λz: termination half-life of IONIS-ENaCRx', 'timeFrame': 'Up to 113 Days'}, {'measure': 'The amount of administered dose of IONIS-ENaCRx excreted in urine over a 24-hour period', 'timeFrame': 'Up to 113 Days'}]}, 'oversightModule': {'isUsExport': True, 'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['ION-827359', 'ENaC'], 'conditions': ['Healthy Subjects', 'Cystic Fibrosis']}, 'descriptionModule': {'briefSummary': 'This Phase 1/2a study is a double-blinded (subject and Investigator), randomized, placebo-controlled, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple nebulized doses of IONIS-ENaCRx.', 'detailedDescription': 'This study will be conducted in 3 parts: a single ascending dose (SAD) leading to a multiple ascending dose (MAD) in healthy volunteers, followed by a MAD in patients with cystic fibrosis. The study will enroll up to 88 participants.\n\nThe study will consist of 4 single-dose randomized cohorts. Participants enrolled will receive a single inhaled dose of the Study Drug (IONIS-ENaCRx or placebo) on Day 1.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT'], 'maximumAge': '50 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': "Inclusion Criteria (Healthy Volunteers)\n\n1. Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal.\n2. Males must be surgically sterile or, abstinent or, if engaged in sexual relations with a woman of child-bearing potential, the subject or the subject's non-pregnant female partner must be using a highly effective contraceptive method\n3. Willing to refrain from strenuous exercise/activity for at least 72 hours prior to study visits\n4. Body mass index (BMI) \\< 35 kg/m2 with a minimum weight of 45 kg\n5. Normal diffusing capacity in the lung (≥ 80% predicted) at Screening\n\nExclusion Criteria (Healthy Volunteers)\n\n1. Clinically-significant (CS) abnormalities in medical history, screening laboratory results, physical or physical examination that would render a subject unsuitable for inclusion, including but not limited to:\n\n 1. Urine protein/creatinine (P/C) ratio ≥ 0.2 mg/mg\n 2. Positive test (including trace) for blood on urinalysis\n 3. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, alkaline phosphatase (ALP), serum creatinine, blood urea nitrogen (BUN), fasting blood glucose, potassium \\> upper limit of normal (ULN)\n 4. Platelet count \\< LLN\n2. Active infection requiring systemic antiviral or antimicrobial therapy that will not be completed prior to Study Day 1\n3. Respiratory infection within 4 weeks of Study Day 1\n4. Presence or past history of CS chronic respiratory disease, including any current history (or within 2 years) of asthma. History of allergic rhinitis is acceptable\n5. Forced expiratory volume in 1 second (FEV1) \\< 80% of predicted at Screening or an FEV1/FVC ratio of \\< 0.7\n6. Smoking of a tobacco or nicotine-containing product within the previous 6 months (use of a nicotine patch is permitted) or a smoking history of ≥ 10 pack years\n7. Any CS finding on chest radiograph\n8. Uncontrolled hypertension (blood pressure \\[BP\\] \\> 160/100 mm Hg) at Screening\n9. Treatment with another investigational drug, biological agent, or device within one month of screening, or 5 half-lives of investigational agent, whichever is longer\n10. Any history of previous treatment with an oligonucleotide\n11. Regular use of alcohol within 6 months prior to screening or hard drugs within 1 year prior to screening, or positive urine drug screen at Screening\n12. Blood donation of 50 to 499 mL within 30 days of screening or of \\> 499 mL within 60 days of screening\n\nInclusion Criteria (Cystic Fibrosis Participants)\n\n1. Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal.\n2. Males must be surgically sterile or, abstinent or, if engaged in sexual relations with a woman of child-bearing potential, the subject or the subject's non-pregnant female partner must be using a highly effective contraceptive method\n3. Confirmed diagnosis of CF by seat chloride and/or genetics by referring clinician\n4. FEV1 \\>/= 50% of predicted\n5. Stable CF disease as judged by the Investigator\n6. Weight \\> 40 kg\n\nExclusion Criteria (Cystic Fibrosis Participants)\n\n1. Clinically-significant (CS) abnormalities in medical history, screening laboratory results, physical or physical examination that would render a subject unsuitable for inclusion, including but not limited to:\n\n 1. Abnormal liver function defined as \\> 2 times upper limit of normal (ULN) for bilirubin, or 3 time ULN for ALT, AST, or alkaline phosphatase\n 2. Platelet count \\< LLN\n2. Active infection requiring systemic antiviral or antimicrobial therapy that will not be completed prior to Study Day 1\n3. Respiratory infection within 4 weeks of Study Day 1\n4. Colonization with Burkholderia cepacia or M. abscessus"}, 'identificationModule': {'nctId': 'NCT03647228', 'briefTitle': 'A Phase 1/2a Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of IONIS-ENaCRx in Healthy Volunteers and Patients With Cystic Fibrosis', 'organization': {'class': 'INDUSTRY', 'fullName': 'Ionis Pharmaceuticals, Inc.'}, 'officialTitle': 'A Double-Blind, Placebo-Controlled, Dose-Escalation, Phase 1/2a Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of ION-827359, an Antisense Oligonucleotide Inhibitor of ENaC, Administered to Healthy Volunteers and Patients With Cystic Fibrosis', 'orgStudyIdInfo': {'id': 'ION-827359-CS1'}, 'secondaryIdInfos': [{'id': '2018-002621-27', 'type': 'EUDRACT_NUMBER'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'IONIS-ENaCRx', 'description': 'Ascending single and multiple doses of IONIS-ENaCRx inhaled or nebulized.', 'interventionNames': ['Drug: IONIS-ENaCRx']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', 'description': 'Placebo comparator calculated volume to match active comparator inhaled or nebulized.', 'interventionNames': ['Drug: Placebo']}], 'interventions': [{'name': 'IONIS-ENaCRx', 'type': 'DRUG', 'description': 'Ascending single and multiple doses of IONIS-ENaCRx inhaled or nebulized.', 'armGroupLabels': ['IONIS-ENaCRx']}, {'name': 'Placebo', 'type': 'DRUG', 'description': 'Placebo comparator calculated volume to match active comparator inhaled or nebulized.', 'armGroupLabels': ['Placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': '45239', 'city': 'Essen', 'country': 'Germany', 'facility': 'Universitätsmedizin Essen', 'geoPoint': {'lat': 51.45657, 'lon': 7.01228}}, {'zip': 'D-60589', 'city': 'Frankfurt', 'country': 'Germany', 'facility': 'Universitätsklinikum Frankfurt', 'geoPoint': {'lat': 49.68333, 'lon': 10.53333}}, {'zip': '81241', 'city': 'München', 'country': 'Germany', 'facility': 'Lungenheilkunde München-Pasing', 'geoPoint': {'lat': 51.60698, 'lon': 13.31243}}, {'zip': 'M23 9QZ', 'city': 'Wythenshawe', 'state': 'Manchester', 'country': 'United Kingdom', 'facility': 'Medicines Evaluation Unit', 'geoPoint': {'lat': 53.38027, 'lon': -2.2654}}, {'zip': 'BT9 6AD', 'city': 'Belfast', 'state': 'Northern Ireland', 'country': 'United Kingdom', 'facility': 'Celerion', 'geoPoint': {'lat': 54.59682, 'lon': -5.92541}}, {'zip': 'EH4 2XU', 'city': 'Edinburgh', 'country': 'United Kingdom', 'facility': 'Western General Hospital', 'geoPoint': {'lat': 55.95206, 'lon': -3.19648}}, {'zip': 'SE5 9RS', 'city': 'London', 'country': 'United Kingdom', 'facility': "Adults Cystic Fibrosis King's College Hospital - Hambleden Wing (East)", 'geoPoint': {'lat': 51.50853, 'lon': -0.12574}}, {'zip': 'SW3 6HP', 'city': 'London', 'country': 'United Kingdom', 'facility': 'Royal Brompton Hospital', 'geoPoint': {'lat': 51.50853, 'lon': -0.12574}}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Ionis Pharmaceuticals, Inc.', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}