[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"leadSponsorName\":\"Aplagon Oy\",\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:":68},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,2,0,[8,42],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":15,"eligibilityCriteria":16,"healthyVolunteers":11,"sex":17,"minAge":4,"maxAge":18,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":25,"conditions":26,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":30,"lastUpdatePostDateStruct":31,"startDateStruct":34,"completionDateStruct":36,"leadSponsor":38,"locationsCount":41},"100620067","phase-2-safety-of-antithrombotic-heparin-proteoglycan-mimetic-apac-in-peripheral-arterial-occlusive-disease-and-chronic-limb-threatening-ischemia-100620067",false,"NCT07352800","Safety of Antithrombotic Heparin Proteoglycan Mimetic APAC in Peripheral Arterial Occlusive Disease and Chronic Limb-threatening Ischemia","A Phase 2a Open-label Study to Assess the Safety, Tolerability, and Dosing Regimen of Antithrombotic Heparin Proteoglycan Mimetic APAC in Patients With Peripheral Arterial Occlusive Disease and Chronic Limb-threatening Ischemia Undergoing Endovascular Revascularization","HEALING","Inclusion Criteria (Parts A1, B1 and B2):\n\n1. Males aged 45-85 years and postmenopausal females (i.e., no menstrual periods for 12 months without an alternative medical cause) up to 85 years.\n2. Diagnosed with a. PAOD classification Fontaine stage III or IV , b. the total length of the treatment-targeted arterial segment ≥ 5 cm below the knee lesion(s) based on contrast-enhanced computed tomography angiography (CTA)\u002Fmagnetic resonance angiography (MRA)\u002Fdigital subtraction angiography (DSA) (Part B1 and B2), c. superficial forefoot wounds without overt infection and bone invasion (WIfI 0-1 and 2 limited to digits and WIfI infection 0-1) allowed, d. undergoing endovascular intervention. (In Part A1, if prescheduled endovascular intervention would take place before the Day 8 study visit, patient is not to be enrolled.)\n3. CTA\u002FMRA\u002FDSA with contrast agent performed within 3 months prior to study enrolment as part of diagnostics of PAOD, with results available in the patient's medical records.\n4. Patients should be treated with antithrombotic medication either acetylsalicylic acid (up to 100 mg once a day \\[QD\\]) or clopidogrel (up to 75 mg QD) for at least the preceding five days before the first APAC administration.\n5. Adequate lipid lowering therapy, as evaluated by the investigator.\n6. Capability and willingness to provide valid, voluntary written informed consent for the study.\n7. Males must be willing to use a condom and their female partners of childbearing potential (i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile \\[hysterectomy, bilateral salpingectomy and bilateral oophorectomy\\]) must be willing to use highly effective contraception while on study treatment. Highly effective methods include: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable); intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomized partner; and sexual abstinence.\n8. Males must refrain from sperm donation while on study treatment.\n\nInclusion Criteria (Part A2):\n\n1. Males aged 45-85 years and postmenopausal females (i.e., no menstrual periods for 12 months without an alternative medical cause) up to 85 years.\n2. Diagnosed with a. PAOD classification Fontaine stage IIa and IIb, b. not prescheduled for endovascular revascularization within 90 days of first APAC administration.\n3. Moderate to severe arterial disease, ABI \\\u003C 0.7.\n4. Patients should be capable of performing evaluable treadmill exercise test.\n5. Patients should be treated with antithrombotic medication either acetylsalicylic acid (up to 100 mg QD) or clopidogrel (up to 75 mg QD) for at least the preceding five days before the first APAC administration.\n6. Adequate lipid lowering therapy, as evaluated by the investigator.\n7. Capability and willingness to provide valid, voluntary written informed consent for the study.\n8. Males must be willing to use a condom and their female partners of childbearing potential (i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile \\[hysterectomy, bilateral salpingectomy and bilateral oophorectomy\\]) must be willing to use highly effective contraception while on study treatment. Highly effective methods include: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable); IUD; IUS; bilateral tubal occlusion; vasectomized partner; and sexual abstinence.\n9. Males must refrain from sperm donation while on study treatment.\n\nExclusion Criteria:\n\n1. Any ischemic lesions of the heel and midfoot and lesions (wounds or gangrene) invading bones, joints, or tendons at metatarsophalangeal joints or more proximal sites.\n2. Acute limb-threatening ischemia (e.g., thromboembolic disease).\n3. Medical history of, or an existing aneurysm.\n4. Endovascular revascularization intervention is done from the contralateral side using cross-over access (Part B1 and B2).\n5. Medical history of, or condition known to be associated with impaired hemostasis, i.e., increased intracranial bleeding risk e.g., previous history of intracranial hemorrhage, subarachnoidal bleeding, hemorrhagic stroke, thrombotic or thromboembolic stroke, gastrointestinal bleeding within 6 months of enrolment, or retroperitoneal bleeding any time, or any inherited or acquired bleeding disorder, i.e., von Willebrand disease or hemophilia or other relevant diagnosis causing impaired hemostasis.\n6. Current use of therapeutic dose of anticoagulation (warfarin, apixaban, rivaroxaban, dabigatran, edoxaban, fondaparinux, or any heparin derivative) for any medical reason. (Use of dual pathway inhibition \\[= acetylsalicylic acid 100 mg + rivaroxabahn 2.5 mg x 2\\] is not a contraindication, but will be temporarily halted for the day of intervention and day of repeating dosing)\n7. Patients treated with combined antiplatelet agents: aspirin + P2Y12 antagonist (clopidogrel, ticagrelor, prasugrel).\n8. Diagnosis of autoimmune diabetes mellitus (Type 1 diabetes, or latent autoimmune diabetes in adults \\[LADA\\]) vasculitis, rheumatoid arthritis, inflammatory bowel diseases, or other general autoimmune diseases.\n9. Body mass index \\> 35 kg\u002Fm\\^2.\n10. Patients with clinically significant acute infection, as judged by the investigator.\n11. Use of non-steroidal anti-inflammatory medications within 2 weeks prior to the first dose of APAC or during the treatment period. If medication for pain is required, paracetamol or tramadol (e.g. an opioid patch) may be used.\n12. Use of selective serotonin reuptake inhibitor (SSRI) medication within 2 weeks prior to the first dose of APAC or during the treatment period.\n13. Peroral use of glycosaminoglycans or omega 3 or related products within 28 days before IMP treatment.\n14. Major surgery, major trauma or any endovascular intervention within the past 90 days or organ biopsy prior to the screening visit or scheduled for such an intervention during the study.\n15. Uncontrolled arterial hypertension (systolic blood pressure \\>160 mmHg or diastolic blood pressure \\>100 mmHg).\n16. Blood hemoglobin concentration \\\u003C120 g\u002FL or \\> 170 g\u002FL (men) and \\\u003C110 g\u002FL or \\>160 g\u002FL (women) at screening.\n17. Blood platelet count \\\u003C150 x 10\\^9\u002FL or \\> 450 x10\\^9\u002FL and\u002For leukocyte count in the lower reference range or not above \\>12 x 10\\^9\u002FL.\n18. Clinically significantly prolonged plasma PT (\\> 1.2-fold) or a value of less than 50% (when normal reference range is 70-130%).\n19. APTT above the upper limit of the reference range.\n20. Patients with a medical history of heparin-induced thrombocytopenia.\n21. Patients with known significant liver disease, incl. an alanine aminotransferase (ALT) and\u002For aspartate aminotransferase (AST) level \\> 2.5 x the upper limit of normal (ULN) at screening.\n22. A diagnosis of severe chronic kidney disease, defined as having an eGFR category 4 or 5 (eGFR \\\u003C 30 mL\u002Fmin\u002F1.73 m2 as per calculation of Chronic Kidney Disease Epidemiology Collaboration \\[CKD-EPI\\]) or albuminuria stage A3 (uACR \\>300 mg\u002Fg).\n23. Patients with an active malignancy, or who have received treatment for any malignancy including bone marrow transplantation within 5 years before the screening visit, except for localized basal cell or squamous cell skin cancer that has been cured at least 90 days before screening.\n24. Previous treatment with APAC.\n25. Patients with known allergy or hypersensitivity to heparin, or heparin products, APAC, and\u002For antiplatelet agents (e.g., aspirin or clopidogrel), and protamine sulphate, the reversal agent for APAC.\n26. Participation in an investigational drug or device study within 90 days prior to screening.\n27. Patients who have ever received treatment with a gene therapy.\n28. Patients with known antiphospholipid antibody syndrome or other known significant thrombophilia (homozygosity for FV Leiden or FIIG20210A mutation, or phospholipid antibody syndrome, deficiency of antithrombin, protein C or protein S or combined thrombophilia).\n29. Any concomitant disease or condition or treatment that could interfere with, or the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the patient in this study as judged by the investigator.\n30. Patients with severe comorbidities and limited life expectancy as judged by the investigator.\n31. Patients unable or unwilling to comply with the protocol or to cooperate fully with the investigator or site personnel.\n32. Patients with current and\u002For history of drug abuse (defined as illicit drug use) or alcohol abuse (defined as daily consumption of more than 23-24 and 12-16 alcoholic drinks per week in males and females, respectively).","ALL","85 Years",{"count":20,"type":21},42,"ESTIMATED","INTERVENTIONAL",[24],"PHASE2","The goal of this study is to learn if a new medicine (called antiplatelet and anticoagulant \\[APAC\\]) can help the body to prevent blood clots and whether APAC is safe and well tolerated in patients with blocked or narrowed arteries in their legs (peripheral arterial occlusive disease \\[PAOD\\]), and in patients with severely restricted poor blood flow to the legs that threatens limb health (chronic limb-threatening ischemia \\[CTLI\\]). The study also aims to find the best dose of the medicine. The study consists of two parts: Part A will include patients with PAOD and CTLI, Part B will only include patients with CTLI who are having a procedure to restore blood flow in their legs. Both parts will be subdivided into two subgroups (A1 and A2, B1 and B2) which will test different APAC doses and compare single dosing to weekly dosing for 4 weeks. APAC is injected into the blood. The possible treatment response will be compared either to a placebo (a look-alike substance that contains no drug), or to the current standard treatment. Patients will participate in the study for up to 90 or 180 days. During this time, patients will be regularly examined and asked to answer questions concerning their quality of life.",[27,28],"Peripheral Arterial Occlusive Disease","Chronic Limb-Threatening Ischemia","RECRUITING","2026-04-08",{"date":32,"type":33},"2026-04-09","ACTUAL",{"date":35,"type":33},"2026-01-29",{"date":37,"type":21},"2027-06-30",{"name":39,"class":40},"Aplagon Oy","INDUSTRY",3,{"id":43,"slug":44,"hasResults":11,"nctId":45,"briefTitle":46,"officialTitle":47,"acronym":48,"eligibilityCriteria":49,"healthyVolunteers":50,"sex":17,"minAge":51,"maxAge":18,"enrollmentInfo":52,"targetDuration":4,"studyType":22,"phases":54,"briefSummary":56,"conditions":57,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":59,"lastUpdatePostDateStruct":60,"startDateStruct":62,"completionDateStruct":64,"leadSponsor":66,"locationsCount":67},"100531779","early-phase-1-safety-tolerability-and-biodistribution-of-89zrzr-dfo-apac-in-subjects-with-paodcli-and-healthy-volunteers-acronyms-89zr--zirconium-89-dfo--desferrioxamine-apac--antiplatelet-anticoagulant-petct--positron-emission-tomographycomputed-tomography-100531779","NCT06204237","Safety, Tolerability, and Biodistribution of [89Zr]Zr-DFO-APAC in Subjects With PAOD\u002FCLI and Healthy Volunteers (Acronyms: 89Zr = Zirconium-89, DFO = Desferrioxamine, APAC = AntiPlatelet AntiCoagulant, PET\u002FCT = Positron Emission Tomography\u002FComputed Tomography)","Safety, Tolerability, and Biodistribution of [89Zr]Zr-DFO-APAC (Phase 0) in Subjects With Peripheral Arterial Occlusive Disease \u002F Critical Limb Ischemia (PAOD\u002FCLI) and Healthy Volunteers - an Open Label PET Study (Acronyms: 89Zr = Zirconium-89, DFO = Desferrioxamine, APAC = AntiPlatelet AntiCoagulant, PET\u002FCT = Positron Emission Tomography\u002FComputed Tomography)","CHASE","INCLUSION CRITERIA PATIENTS\n\n1. Males and females aged 40-85 years.\n2. PAOD\u002FCLI patients Rutherford categories 1-4 and category 5 with Wlfl wound grade of 0 or 1.\n3. Estimated glomerular filtration rate (eGFR) \\>46 mL\u002Fmin\u002F1.73 m2 as per calculation of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI).\n4. CT angiography with contrast agent performed of within 3 months of the patients' first PET-scan as part of diagnostics of PAOD, with results available in the subject's medical records.\n5. No surgical or endovascular intervention for PAOD within 1 year of the first PET\u002FCT-scan or planned between inclusion and the patients' last PET-scan.\n6. Provision of valid informed consent and capability to communicate well with the investigator.\n7. Pre-menopausal woman must be willing to practise highly effective contraception for 195 days after IMP administration.\n8. Men must be willing to practise highly effective contraception for 105 days after IMP administration, including condom use during the first 15 days to prevent transmission of 89-Zr to a partner of childbearing potential.\n9. Patients should be able to understand all study-related information in Dutch.\n\nEXCLUSION CRITERIA PATIENTS\n\n1. Acute limb-threatening ischemia (e.g., embolic disease).\n2. An existing aneurysm that requires surgical intervention.\n3. Medical history of, or condition known to be associated with impaired hemostasis, such as an increased intracranial bleeding risk e.g., previous history of intracranial hemorrhage, subarachnoidal bleeding, hemorrhagic stroke, or gastrointestinal or retroperitoneal bleeding, or any inherited or acquired bleeding disorder, such as von Willebrand disease or hemophilia.\n4. Any cerebrovascular event (including transient ischemic attack, thrombotic or embolic stroke) within the past year.\n5. Diagnosis of autoimmune (Type 1, or latent autoimmune diabetes in adults (LADA))diabetes mellitus.\n6. HbA1c \\>10% at screening.\n7. Current use of anticoagulant therapy (warfarin, apixaban, rivaroxaban, dabigatran, edoxaban, fondaparinux, or any heparin derivative) for any medical reason.\n8. Patients treated with combined antiplatelet agents, excluding a single agent, such as acetylsalicylic acid (up to 100 mg QD) or clopidogrel (up to 75 mg QD).\n9. Use of non-steroidal anti-inflammatory medications within 2 weeks prior to dosing with \\[89Zr\\]Zr-DFO-APAC. If pain relief is required, paracetamol may be used.\n10. Use of selective serotonin reuptake inhibitor (SSRI) medications within 2 weeks prior to dosing with \\[89Zr\\]Zr-DFO-APAC.\n11. Major surgery, major trauma or any endovascular intervention within the past 90 days or organ biopsy or diagnostic angiography within the past 30 days prior to the screening visit.\n12. Uncontrolled arterial hypertension (persistent systolic blood pressure \\> 160 mmHg or diastolic blood pressure \\> 100 mmHg).\n13. Hemoglobin \\\u003C8.0 mmol\u002FL (130 g\u002Fl) (men) or \\\u003C7.5 mmol\u002FL (120 g\u002Fl) (women) at screening, or platelet count \\\u003C150 x 109\u002FL and leukocyte count \\>12 x 109\u002FL.\n14. Clinically significantly prolonged plasma prothrombin time (PT) and activated plasma partial thromboplastin time (APTT) (\\> 1.2-fold).\n15. Patients with a medical history of heparin-induced thrombocytopenia.\n16. Patients with known significant liver disease, incl. an alanine aminotransferase (ALT) and\u002For aspartate aminotransferase (AST) level \\> 2.5 x ULN (Upper limit normal) at screening.\n17. A diagnosis of severe chronic kidney disease, defined as having a glomerular filtration rate (GFR) category 4 or 5 (GFR ≤ 45 mL\u002Fmin\u002F1.73 m2) and albuminuria stage A3 albumin:creatinine ratio (ACR) of \\>300 mg\u002Fg).\n18. Patients with an active malignancy or who have received treatment for any malignancy within 1 year before the screening visit, except for localized basal cell or squamous cell skin cancer that has been cured at least 90 days before screening.\n19. Patients with a history of metastatic malignancy.\n20. Women who are pregnant or lactating.\n21. Patients with a known allergy or hypersensitivity to heparin or heparin products, and\u002For antiplatelet agents (e.g., aspirin or clopidogrel).\n22. Participation in an investigational drug or device study within 30 days prior to screening.\n23. Patients who have ever received treatment with an antibody or gene therapy product or participated in a clinical trial with such agents (unless there is evidence that they received placebo only).\n24. Patients with known antiphospholipid antibody syndrome or other thrombophilia.\n25. Patients with a medical history of severe infection or vasculitis due to an autoimmune disease, inflammatory bowel disease (IBD) or Crohn's disease.\n26. Any concomitant disease or condition that could interfere with, or the treatment of which might interfere with, the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject.\n27. Patients unable or unwilling to comply with the protocol or to cooperate fully with the investigator or site personnel.\n28. Patients with anamnestic history of drug abuse (defined as illicit drug use) or anamnestic history of alcohol abuse (defined as regular or daily consumption of more than 4 alcoholic drinks per day) within the past 12 months.\n\nINCLUSION CRITERIA HEALTHY VOLUNTEERS\n\n1. Male or female volunteers 40-80 years old, inclusive.\n2. Healthy status defined by the absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead ECG, hematology, blood chemistry, serology and urinalysis.\n3. No diagnosis of diabetes, pre-diabetes or insulin resistance.\n4. Normal eGFR as per calculation of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI).\n5. Premenopausal woman must be willing to practise highly effective contraception for 195 days after IMP administration.\n6. Men must be willing to practise highly effective contraception for 105 days after IMP administration, including condom use during the first 15 days to prevent transmission of 89-Zr to a partner of childbearing potential\n7. Healthy volunteers should be able to understand all study-related information in Dutch.\n\nEXCLUSION CRITERIA HEALTY VOLUNTEERS\n\n1. Any sign or symptom of PAOD\u002FCLI or other cardiovascular disease.\n2. Abnormal ankle-brachial index (ABI) at rest and\u002For decrease of ABI following treadmill exercise.\n3. Use of any anticoagulant or antiplatelet (not including aspirin at recommended doses) agent within the recent 12 months before screening.\n4. Any regular prescription or over-the-counter medication, except for vitamins.\n5. Medical history of heparin-induced thrombocytopenia.\n6. Medical history of atrial fibrillation and\u002For those with a mechanical heart valve.\n7. Major surgery, major trauma or organ biopsy within the past 90 days before screening.\n8. Medical history of, or any condition, associated with an increased bleeding risk.\n9. Arterial hypertension (systolic blood pressure \\>140 mmHg or diastolic blood pressure \\>90 mmHg.\n10. Subjects with a medical history of, or an existing aneurysm.\n11. Hemoglobin \\\u003C8.0 mmol\u002FL (130 g\u002Fl) (men) or \\\u003C7.5 mmol\u002FL (120 g\u002Fl) (women) at screening or platelet count \\< 150 x 109\u002FL or leukocyte count above normal (12 x 109\u002FL).\n12. Clinically significantly prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT) (\\> 1.2-fold).\n13. Participation in an investigational drug or device study within 30 days prior to screening.\n14. Subjects who have ever received treatment with an antibody or gene therapy product or participated in a clinical trial with such agents (unless there is evidence that they were received placebo only).\n15. Subjects with known thrombophilia.\n16. Women who are pregnant or lactating.\n17. Subjects unable or unwilling to comply with the protocol or to cooperate fully with the investigator or site personnel.\n18. Subjects with anamnestic history of drug abuse (defined as illicit drug use) or a anamnestic history of alcohol abuse (defined as regular or daily consumption of more than 4 alcoholic drinks per day) within the past 3 months.",true,"40 Years",{"count":53,"type":21},10,[55],"EARLY_PHASE1","The goal of this Phase 0 clinical trial is to evaluate safety and biodistribution of \\[89Zr\\]Zr-DFO-APAC in patients with peripheral arterial occlusive disease \u002F critical limb ischemia (PAOD\u002FCLI) and healthy volunteers. The main questions it aims to answer are:\n\n* What is the safety, tolerability and pharmacokinetic profile (PK: both systemic and local vascular injury site-specific PK) of \\[89Zr\\]Zr-DFO-APAC?\n* What is the biodistribution and internal radiation dosimetry of the tracer dose of \\[89Zr\\]Zr-DFO-APAC?\n* What is the binding and retention time of \\[89Zr\\]Zr-DFO-APAC to arteries and atherosclerotic or microvascular lesions? Participants will receive a dose of the \\[89Zr\\]Zr-DFO-APAC (IMP) and PET\u002FCT imaging is performed on days 1, 3 and 7, and follow-up visit 7-14 days post IMP dosing.",[27,58],"Critical Limb Ischemia","2025-01-28",{"date":61,"type":33},"2025-01-30",{"date":63,"type":33},"2024-02-01",{"date":65,"type":21},"2025-06",{"name":39,"class":40},1,""]