Ignite Creation Date:
2025-12-26 @ 11:07 AM
Ignite Modification Date:
2025-12-29 @ 5:48 AM
Study NCT ID:
NCT05876312
Status:
RECRUITING
Last Update Posted:
2024-11-15
First Post:
2023-05-17
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Safety, Tolerability, PK and PD of ADX-038 in Healthy Participants and Paroxysmal Nocturnal Hemoglobinuria (PNH) Patients
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D006457', 'term': 'Hemoglobinuria, Paroxysmal'}], 'ancestors': [{'id': 'D000743', 'term': 'Anemia, Hemolytic'}, {'id': 'D000740', 'term': 'Anemia'}, {'id': 'D006402', 'term': 'Hematologic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}, {'id': 'D009190', 'term': 'Myelodysplastic Syndromes'}, {'id': 'D001855', 'term': 'Bone Marrow Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D034741', 'term': 'RNA, Small Interfering'}, {'id': 'D012965', 'term': 'Sodium Chloride'}], 'ancestors': [{'id': 'D016372', 'term': 'RNA, Antisense'}, {'id': 'D016375', 'term': 'Antisense Elements (Genetics)'}, {'id': 'D009706', 'term': 'Nucleic Acids, Nucleotides, and Nucleosides'}, {'id': 'D012313', 'term': 'RNA'}, {'id': 'D009696', 'term': 'Nucleic Acids'}, {'id': 'D058727', 'term': 'RNA, Small Untranslated'}, {'id': 'D022661', 'term': 'RNA, Untranslated'}, {'id': 'D002712', 'term': 'Chlorides'}, {'id': 'D006851', 'term': 'Hydrochloric Acid'}, {'id': 'D017606', 'term': 'Chlorine Compounds'}, {'id': 'D007287', 'term': 'Inorganic Chemicals'}, {'id': 'D017670', 'term': 'Sodium Compounds'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1', 'PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR'], 'maskingDescription': 'Masking is only applicable to Phase 1 in HP. Phase 2a is open label and there is no masking.'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Model Description'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 50}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2023-08-07', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-11', 'completionDateStruct': {'date': '2026-09-30', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2024-11-12', 'studyFirstSubmitDate': '2023-05-17', 'studyFirstSubmitQcDate': '2023-05-17', 'lastUpdatePostDateStruct': {'date': '2024-11-15', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2023-05-25', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2026-03-30', 'type': 'ESTIMATED'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Immune Response in Healthy Participants', 'timeFrame': '365 days', 'description': 'Anti-polyethylene glycol (PEG) antibody titers and anti-drug antibody titers'}, {'measure': 'Pharmacodynamics in Healthy Participants', 'timeFrame': '365 days', 'description': 'Change in complement classical pathway activity via assay measurement'}, {'measure': 'Safety in Paroxysmal Nocturnal Hemoglobinuria Participants', 'timeFrame': '365 days', 'description': 'Evaluate the change from baseline in follow up visits for safety assesments'}, {'measure': 'Clinical Effect in Paroxysmal Nocturnal Hemoglobinuria Participants', 'timeFrame': '365 days', 'description': 'Look at time (number of days) from dosing (Day 1) to diminished therapeutics effect (DTE)'}, {'measure': 'Efficacy in Paroxysmal Nocturnal Hemoglobinuria Participants', 'timeFrame': '365 days', 'description': 'Evaluate changes in lactate dehydrogenase (LDH) (U/L)'}, {'measure': 'Effects on Hemolysis in Paroxysmal Nocturnal Hemoglobinuria Participants', 'timeFrame': '365 days', 'description': 'Evaluate incidence of clinical breakthrough hemolysis, blood transfusions and Incidence of major adverse vascular events (MAVEs)'}, {'measure': 'Pharmacokinetics in Paraxysmal Nocturnal Hemoglobinuria', 'timeFrame': '8 days', 'description': 'Characterize PK parameters of ADX-038 by plasma C(max)'}, {'measure': 'Pharmacodynamics in Paraxysmal Nocturnal Hemoglobinuria', 'timeFrame': '365 days', 'description': 'Characterize changes in complement classical pathway activity level'}, {'measure': 'Immune Response in Paraxysmal Nocturnal Hemoglobinuria', 'timeFrame': '365 days', 'description': 'Determine Anti-PEG and anti-drug antibody titers'}, {'measure': 'Efficacy in Paroxysmal Nocturnal Hemoglobinuria Participants', 'timeFrame': '365 days', 'description': 'Evaluate changes in serum free hemoglobin'}, {'measure': 'Efficacy in Paroxysmal Nocturnal Hemoglobinuria Participants', 'timeFrame': '365 days', 'description': 'Evaluate changes in Haptoglobin Concentrations'}, {'measure': 'Efficacy in Paroxysmal Nocturnal Hemoglobinuria Participants', 'timeFrame': '365 days', 'description': 'Evaluate changes in Reticulocyte Counts (%)'}, {'measure': 'Efficacy in Paroxysmal Nocturnal Hemoglobinuria Participants', 'timeFrame': '365 days', 'description': 'Evaluate changes in Bilirubin (umol/L)'}, {'measure': 'Efficacy in Paroxysmal Nocturnal Hemoglobinuria Participants', 'timeFrame': '365 days', 'description': 'Evaluate changes in Aspartate aminotransferase (U/L)'}, {'measure': 'Pharmacokinetics in Paraxysmal Nocturnal Hemoglobinuria', 'timeFrame': '8 days', 'description': 'Characterize PK parameters of ADX-038 by plasma AUC (0-infinity)'}, {'measure': 'Pharmacokinetics in Paraxysmal Nocturnal Hemoglobinuria', 'timeFrame': '8 days', 'description': 'Characterize PK parameters of ADX-038 by plasma AUC(0-last)'}, {'measure': 'Pharmacokinetics in Paraxysmal Nocturnal Hemoglobinuria', 'timeFrame': '8 days', 'description': 'Characterize PK parameters of ADX-038 by plasma T(max)'}], 'primaryOutcomes': [{'measure': 'Safety in Healthy Volunteers', 'timeFrame': '365 days', 'description': 'To evaluate the safety and tolerability of ADX-038 in HVs by incidence, relationship, and severity of adverse events and serious adverse events'}, {'measure': 'Safety in Paroxysmal Nocturnal Hemoglobinuria Participants', 'timeFrame': '365 days', 'description': 'Evaluate the safety and tolerability of ADX-038 by incidence, relationship, and treatment-emergent adverse events and serious adverse events.'}], 'secondaryOutcomes': [{'measure': 'Pharmacokinetics in Healthy Participants', 'timeFrame': '8 days', 'description': 'To characterize the Pharmacokinetics of ADX-038 in HPs by measuring the Maximum observed plasma concentration (Cmax)'}, {'measure': 'Pharmacodynamics in Healthy Participants', 'timeFrame': '365 days', 'description': 'Change from base in plasma concentrations over time in Complement factor B (CFB) protein via assay measurement'}, {'measure': 'Pharmacodynamics in Paraxysmal Nocturnal Hemoglobinuria', 'timeFrame': '365 days', 'description': 'Evaluate the changes in hemoglobin concentrations'}, {'measure': 'Pharmacodynamics in Paraxysmal Nocturnal Hemoglobinuria', 'timeFrame': '365 days', 'description': 'Characterize the changes in serum concentration of complement factor B (CFB) protein and complement alternative pathway activity level.'}, {'measure': 'Pharmacodynamics in Healthy Participants', 'timeFrame': '365 days', 'description': 'Change in complement alternative pathway activity via assay measurement'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['siRNA', 'PNH'], 'conditions': ['Paroxysmal Nocturnal Hemoglobinuria (PNH)']}, 'descriptionModule': {'briefSummary': 'The first-in-human Phase 1/Phase 2a study described herein will evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of ADX-038 in both healthy participants (HP) and in patients with paroxysmal nocturnal hemoglobinuria (PNH).', 'detailedDescription': 'The clinical study described in this protocol is a Phase 1/Phase 2a study evaluating safety, tolerability, PK, and PD of ADX-038.\n\nThe study consists of 2 parts:\n\n1. Phase 1 - Randomized, double-blind, placebo-controlled, parallel group, single ascending dose (SAD) in HP with up to 5 dose cohorts.\n2. Phase 2a - Open label, single-arm (ADX-038), 2 dose study in participants with paroxysmal nocturnal hemoglobinuria (PNH) and residual anemia on a standard-of-care (SOC) anti-C5 regimen of ravulizumab or eculizumab.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Phase 1 Key Inclusion Criteria\n\n* 18 to 55 years of age\n* Participants who are healthy as determined by medical evaluation\n* History of recent meningococcal, pneumococcal and Haemophilus influenzae type B vaccinations or willing to be vaccinated\n* Screening tests negative for illicit drug, nicotine, and alcohol use\n\nPhase 1 Key Exclusion Criteria\n\n* History of any significant medical conditions, except for completely excised non-melanoma skin cancer or low grade cervical intraepithelial neoplasia without evidence of recurrence within the prior 3 months\n* Any viral, bacterial, parasitic, or fungal infection within the prior 30 days\n* Frequent respiratory, nasopharyngeal or ear infections (more than 5 infections per year)\n* History of environmental exposure or sick contact that increase the risk of meningococcal, pneumococcal and/or Haemophilus influenza type B infections\n* Complement deficiency or immunodeficiency syndrome\n* Major surgery or significant traumatic injury within the prior 3 months\n* History of anaphylaxis or hypersensitivity reactions\n* History of penicillin allergy\n* History of splenectomy\n* History of alcohol abuse or illicit drug use\n* Donated plasma within the prior 7 days\n* Donated blood or loss more than 400 milliliters of blood (excluding blood volume drawn at screening) within the prior 90 days\n* Screening estimated creatinine clearance of less than 60 milliliters per minute\n* Screening hematology, serum chemistry, or coagulation parameters that are outside the normal range\n* Screening vital signs that are abnormal per protocol specification\n* Screening electrocardiogram findings that are clinically significant\n* Pregnant or lactating females\n* Use of prescription (except for contraceptives and study-related prophylactic antibiotics) or over-the counter medications (except for paracetamol or ibuprofen) or vitamins/supplements within the prior 7 days\n* Use of medications that may reduce the effectiveness of hormonal contraceptives within the prior 28 days\n* Use of an investigational therapeutics within the prior 30 days or within the expected washout (at least 5 half-lives)\n* Unwilling or unable to adhere to study-related prophylactic antibiotics requirements\n\nPhase 2a Key Inclusion Criteria\n\n* at least 18 years of age\n* Diagnosis of paroxysmal nocturnal hemoglobinuria based on documented clone size\n* Hemoglobin concentration of less than 12 gram per deciliter\n* History of recent meningococcal, pneumococcal and Haemophilus influenzae type b vaccinations or willing to be vaccinated\n* On a stable anti-C5 regimen for greater than or equal to 12 weeks prior to Day 1\n\nPhase 2a Key Exclusion Criteria\n\n* Any viral, bacterial, parasitic, or fungal infection within the prior 14 days\n* HIV, active hepatitis C or hepatitis B infection\n* History of meningococcal or tuberculosis infection\n* History of malignancy in the past 5 years, except for completely excised non-melanoma skin cancer or low grade cervical intraepithelial neoplasia with no evidence of recurrence within the prior 3 months\n* Complement deficiency syndrome\n* History of hematopoietic stem cell transplantation\n* History of splenectomy\n* Inflammatory bowel disease, systemic lupus erythematosus, rheumatoid arthritis, or chronic liver disease\n* Clinically significant and uncontrolled medical conditions including, but not limited to, thromboembolic disease, acute coronary syndrome, and diabetes\n* Pregnant or lactating females\n* Use of an investigational therapeutics within the prior 30 days or within the expected washout period (at lest 5 half-lives)\n* Abstain from alcohol consumption for 48 hrs before day of dosing and restrict to no more than an average of 14 standard drinks per week'}, 'identificationModule': {'nctId': 'NCT05876312', 'acronym': 'PNH', 'briefTitle': 'Safety, Tolerability, PK and PD of ADX-038 in Healthy Participants and Paroxysmal Nocturnal Hemoglobinuria (PNH) Patients', 'organization': {'class': 'INDUSTRY', 'fullName': 'ADARx Pharmaceuticals, Inc.'}, 'officialTitle': 'A Phase 1, Randomized, Double Blind, Placebo-Controlled, Single Ascending Dose Study in Healthy Participants Followed by a Phase 2a Open Label Study in Participants with PNH and Residual Anemia to Evaluate the Safety, Tolerability, PK and PD of ADX-038', 'orgStudyIdInfo': {'id': 'ADX-038-101'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Phase 1 - Active ADX-038 administered to HP', 'description': "For each cohort in Phase 1 (SAD), 8 participants will be randomized in a 3:1 ratio; 6 participants to active (ADX-038): 2 participants to control (matched placebo). Randomization will be on Day 1. Initially, 2 sentinel participants (1 active and 1 placebo) will be randomized and dosed. The sentinel participants will be evaluated for safety. The investigator's assessment and the independent medical monitor will decide upon the randomization and dosing of the 6 remaining participants (5 active and 1 placebo) according to the randomization schedule.", 'interventionNames': ['Drug: ADX-038']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Phase 1- Placebo administered to HP', 'description': "For each cohort in Phase 1 (SAD), 8 participants will be randomized in a 3:1 ratio; 6 participants to active (ADX-038): 2 participants to control (matched placebo). Randomization will be on Day 1. Initially, 2 sentinel participants (1 active and 1 placebo) will be randomized and dosed. The sentinel participants will be evaluated for safety. The investigator's assessment and the independent medical monitor will decide upon the randomization and dosing of the 6 remaining participants (5 active and 1 placebo) according to the randomization schedule.", 'interventionNames': ['Drug: Placebo']}, {'type': 'EXPERIMENTAL', 'label': 'Phase 2a - ADX-038 administered to PNH participants', 'description': 'This will be initiated at the dose level determined by the Safety Review Committee from SAD in HPs. The treatment of PNH participants is an open-label study.', 'interventionNames': ['Drug: ADX-038']}], 'interventions': [{'name': 'ADX-038', 'type': 'DRUG', 'otherNames': ['siRNA'], 'description': 'siRNA duplex oligonucleotide', 'armGroupLabels': ['Phase 1 - Active ADX-038 administered to HP', 'Phase 2a - ADX-038 administered to PNH participants']}, {'name': 'Placebo', 'type': 'DRUG', 'otherNames': ['Saline'], 'description': 'Saline', 'armGroupLabels': ['Phase 1- Placebo administered to HP']}]}, 'contactsLocationsModule': {'locations': [{'zip': '4006', 'city': 'Brisbane', 'state': 'Queensland', 'status': 'RECRUITING', 'country': 'Australia', 'contacts': [{'name': 'Richard Friend, MD', 'role': 'CONTACT', 'email': 'rfriend@nucleusnetwork.com.au', 'phone': '+61 403 415 925'}], 'facility': 'Nucleus Network Brisbane', 'geoPoint': {'lat': -27.46794, 'lon': 153.02809}}, {'zip': '3000', 'city': 'Melbourne', 'state': 'Victoria', 'status': 'NOT_YET_RECRUITING', 'country': 'Australia', 'contacts': [{'name': 'Jeff Szer, MD', 'role': 'CONTACT', 'email': 'PCCTU.HaemA@petermac.org', 'phone': '+61385595000'}], 'facility': 'Peter MacCallum Cancer Centre', 'geoPoint': {'lat': -37.814, 'lon': 144.96332}}, {'zip': '3052', 'city': 'Parkville', 'state': 'Victoria', 'status': 'NOT_YET_RECRUITING', 'country': 'Australia', 'contacts': [{'name': 'Jeff Szer, MD', 'role': 'CONTACT', 'email': 'PCCTU.HaemA@petermac.org', 'phone': '+61385595000'}], 'facility': 'Royal Melbourne Hospital', 'geoPoint': {'lat': -37.78333, 'lon': 144.95}}, {'zip': 'SE1 1YR', 'city': 'London', 'state': 'London', 'status': 'RECRUITING', 'country': 'United Kingdom', 'contacts': [{'name': 'Ulrike Lorch, MD', 'role': 'CONTACT'}, {'name': 'Matej Goricar, MD', 'role': 'CONTACT'}], 'facility': 'Richmond Pharmacology Ltd', 'geoPoint': {'lat': 51.50853, 'lon': -0.12574}}], 'centralContacts': [{'name': 'Richard Friend, MD', 'role': 'CONTACT', 'email': 'r.friend@nucleusnetwork.com.au', 'phone': '+61 403 415 925'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'ADARx Pharmaceuticals, Inc.', 'class': 'INDUSTRY'}, 'collaborators': [{'name': 'ADARx Australia Pty Ltd', 'class': 'UNKNOWN'}, {'name': 'Novotech (Australia) Pty Limited', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'SPONSOR'}}}}