[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"leadSponsorName\":\"Pharming Technologies B.V.\",\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:":94},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,3,0,[8,47,70],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":15,"eligibilityCriteria":16,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":25,"conditions":26,"keywords":28,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":35,"lastUpdatePostDateStruct":36,"startDateStruct":39,"completionDateStruct":41,"leadSponsor":43,"locationsCount":46},"100489216","phase-2-efficacy-of-kl1333-in-adult-patients-with-primary-mitochondrial-disease-100489216",false,"NCT05650229","Efficacy of KL1333 in Adult Patients With Primary Mitochondrial Disease","An Interventional, Randomised, Double-blind, Parallel-group, Placebo-controlled, Flexible-dose, Adaptive Study of the Efficacy of KL1333 in Adult Patients With Primary Mitochondrial Disease","FALCON","Inclusion Criteria:\n\n* Age 18 years or older.\n* A confirmed PMD diagnosis caused by a known pathogenic gene mutation or deletion of the mitochondrial genome (category 6 of the International Classification of Inborn Metabolic Disorders \\[ICIMD\\])12 according to American College of Medical Genetics (ACMG)\u002FAssociation of Molecular Pathology (AMP) criteria1, with multisystemic disease expressions, including:\n\n  1. m.3243A\\>G associated MELAS-MIDD spectrum disorders,\n  2. single large scale mtDNA deletion associated KSS-CPEO spectrum disorders,\n  3. other multisystemic mtDNA-related disease (including MERRF).\n* Presence of chronic mitochondrial fatigue:\n\n  * History of mitochondrial fatigue for at least 3 months prior to the Screening Visit AND\n  * Presence of at least moderate level of fatigue, assessed by PROMIS® Fatigue PMD Short form raw score ≥ 27 at Screening and Baseline\n* Presence of mitochondrial myopathy defined as:\n\n  * Myopathy (proximal muscle weakness), NMDAS Section III Clinical Assessment, item 5 score ≥ 1, which reads: \"minimal reduction in hip flexion and\u002For shoulder abduction only (e.g. MRC 4+\u002F5)\". For the inclusion only hip flexion, but not shoulder abduction, should be taken into account. AND \u002F OR\n  * Exercise Tolerance: NMDAS Section I, item 9 score ≥ 1, which reads: \"unlimited on flat - symptomatic on inclines or stairs\".\n* Patients must be able to perform at least 2 repetitions and the maximal capacity must not exceed 17 repetitions in males or 16 repetitions in females in a 30s STS test at screening.\n* Clinically stable, apart from symptoms associated with the diagnosis of mitochondrial disease, at Screening and Baseline, as determined by medical history, physical examination, 12-lead ECG, vital signs measurements, and clinical laboratory evaluations at Screening, as assessed by the investigator.\n* The patient is willing and able to attend study appointments within the specified time windows.\n* Willingness and ability to complete electronic PROs.\n* Willingness to maintain a stable diet during the Screening and study periods.\n* Patients who take any mitochondrial disease-focused vitamins or supplemental therapies, including coenzyme Q10 (CoQ10), niacin\u002Fnicotinamide (vitamin B3), and L-arginine, has been on a stable dose regimen of these for 3 months prior to randomisation and intends to stay on a stable dose for the duration of the study period.\n* Willingness to suspend treatment with idebenone during the study.\n* Female patient is not pregnant and at least one of the following conditions apply:\n\n  1. Not a woman of childbearing potential (WOCBP)\n  2. WOCBP must agree not to try and become pregnant and use a highly effective method of contraception from the time of informed consent through at least 36 days (\\~5 half-lives of KL1333 plus 30 days) after the last dose of investigational medicinal product (IMP) administration.\n* Male patients with female partner(s) of childbearing potential must agree to use a male condom in addition to using highly effective contraception throughout the treatment period and for 96 days after the last dose of IMP administration. The requirement to use a male condom also applies to male patients with a pregnant or breastfeeding partner.\n* Female patients must agree not to breastfeed starting at Screening and throughout the study period and for 36 days after the last dose of IMP administration.\n* Female patients must agree to not donate ova throughout the study period and for 36 days after the last dose of IMP administration, and male patients must agree to not donate sperm throughout the study period and for 96 days after the last dose of IMP administration.\n\nExclusion Criteria:\n\n* Primary mitochondrial disease with predominant neurodegenerative phenotypes, such as, but not limited to, Leigh syndrome, Leber hereditary optic neuropathy (LHON) and Neuropathy ataxia-retinitis pigmentosa syndrome (NARP).\n* Primary mitochondrial disease nuclear DNA mutations or mutations causing mtDNA destabilisation. Genetic mtDNA variants of uncertain significance, likely pathogenic, or pathogenic mutations with degrees of heteroplasmy below what can be considered to definitely cause PMD.\n* General fatigue or muscle weakness due to causes other than mitochondrial disease, in the opinion of the investigator.\n* Significant cardiovascular disease (e.g., sustained or symptomatic arrhythmia; dilated heart chambers or reduced function; Mobitz II atrioventricular block or greater) OR abnormal ECG that is clinically significant, as determined by the investigator. Any QTcF \\> 450 msec for male patients and \\> 470 msec for female patients is exclusionary. In the case of an exclusionary QTcF, the ECG can be repeated twice and the average of 3 QTcF intervals should be used to determine the QTcF eligibility.\n* Recent history of unstable disease, inadequately controlled neurological manifestations or not recovered from stroke-like episodes including but not limited to:\n\n  1. stroke-like episodes within the last 6 months\n  2. more than 1 seizure\u002Fmonth within the last 6 months\n  3. hospitalised for Status Epilepticus within the last 6 months\n  4. more than 4 days of migraine episodes\u002Fmonth within the last 6 months\n* History of inflammatory bowel disease, gastric erosions, peptic ulcer disease, or gastrointestinal bleeding episodes. Gastroesophageal reflux disease diagnosed by objective endoscopic or radiographic means, and clinically symptomatic at any point over the last 6 months.\n* The patient has one or more clinical laboratory test values outside the reference range, based on the blood and urine samples taken at the Screening Visit, that are of potential risk to the patient's safety, or the patient has, at the Screening Visit:\n\n  * estimated glomerular filtration rate (eGFR) calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation \\\u003C30 mL\u002Fmin\u002F1.73 m2\n  * a serum total bilirubin value \\> 1.5 times the upper limit of the reference range unless elevation is related to Gilbert's syndrome and the investigator can rule out any underlying liver dysfunction based on other tests, the patient has a Child-Pugh score ≤6, and after discussing the case with the medical monitor\n  * a serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value \\> 2 times the upper limit of the reference range. Values between 2 and 3 times the upper limit of the reference range may be allowed if concomitant to elevation in creatine kinase as long as the investigator can rule out any underlying liver dysfunction based on other tests, the patient has a Child-Pugh score ≤6, and after discussing the case with the medical monitor\n* The patient has, in the investigator's opinion, severe ataxia, neuropathy, balance problems or other medical condition that would interfere the evaluation of the 30s STS test.\n* Untreated or undertreated sleep apnoea, in the opinion of the investigator.\n* Use of idebenone within 14 days prior to the first dose.\n* Patients have a history of unstable or severe pulmonary, immunological, oncological, hepatic disease, renal disease, or another medically significant illness other than PMD or takes medication that could, in the investigator's opinion, interfere with the assessments of safety, tolerability, or efficacy, or interfere with the conduct or interpretation of the study.\n* The patient is, in the investigator's opinion, unlikely to comply with the protocol e.g. due to cognitive impairment or is unsuitable for any reason.\n* The patient has an immediate family member (defined as family members residing at the same address) who participates in the study.\n* Female patients with a positive pregnancy result at Screening or at Baseline.\n* A patient cannot participate if they received an investigational drug 30 days or 5 half-lives prior to the Screening Visit (whichever is longer), or plans to use an investigational drug (other than the study intervention) during the study\n* Hypersensitivity to the active substance or to any of the excipients or placebo.","ALL","18 Years",{"count":20,"type":21},180,"ESTIMATED","INTERVENTIONAL",[24],"PHASE2","The primary objective of the FALCON study is to evaluate the efficacy of KL1333 on selected disease manifestations of primary mitochondrial disease (PMD) following 48 weeks of treatment. This objective involves evaluating the efficacy of KL1333 versus placebo on fatigue symptoms and impacts on daily living as well as on functional lower extremity strength and endurance. Additionally, the study evaluates the safety and tolerability of KL1333.",[27],"Primary Mitochondrial Disease",[29,30,31,32,33],"Chronic fatigue","Myopathy","Muscle weakness","Exercise intolerance","Diabetes","RECRUITING","2026-06-23",{"date":37,"type":38},"2026-06-26","ACTUAL",{"date":40,"type":38},"2022-12-13",{"date":42,"type":21},"2027-11",{"name":44,"class":45},"Pharming Technologies B.V.","INDUSTRY",55,{"id":48,"slug":49,"hasResults":11,"nctId":50,"briefTitle":51,"officialTitle":52,"acronym":53,"eligibilityCriteria":54,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":55,"targetDuration":4,"studyType":22,"phases":57,"briefSummary":58,"conditions":59,"keywords":4,"overallStatus":61,"whyStopped":4,"lastUpdateSubmitDate":62,"lastUpdatePostDateStruct":63,"startDateStruct":65,"completionDateStruct":67,"leadSponsor":69,"locationsCount":4},"100632488","phase-2-open-label-extension-to-assess-long-term-safety-and-efficacy-of-kl1333-in-patients-with-primary-mitochondrial-disease-100632488","NCT07514338","Open Label Extension to Assess Long Term Safety and Efficacy of KL1333 in Patients With Primary Mitochondrial Disease","An Open-label, Single-arm Extension Study to Evaluate the Long-term Safety, Tolerability, and Efficacy of KL1333 (Napazimone) in Patients With Primary Mitochondrial Disease","Falcon-OLE","Inclusion Criteria:\n\n* Completed the FALCON study (age 18 years or older), and in the opinion of the investigator and sponsor has been compliant with the study requirements\n* Willingness and ability to attend study appointments within the specified time windows\n* Willingness and ability to complete electronic patient-reported outcomes\n* Concomitant medications likely to remain stable throughout participation in the study where clinically possible\n* Willingness to suspend treatment with idebenone during the study\n\nExclusion Criteria:\n\n* The subject is, in the investigator's opinion, unlikely to comply with the protocol, e.g., due to cognitive impairment, or is unsuitable for any reason.\n* Any medical, psychiatric, laboratory or other condition that may negatively affect the benefit-risk considerations of study participation or interfere with the interpretation of study results and, in the judgment of the investigator and\u002For the medical monitor, would make the subject inappropriate for entry into this study.\n\nSubjects not enrolling directly at the FALCON study completion visit (FALCON Week 48) or the safety follow-up visit (FALCON Week 53) study will be required to fulfill the additional exclusion criteria below during the screening visit:\n\n• General fatigue or muscle weakness due to causes other than mitochondrial disease, in the opinion of the investigator.",{"count":56,"type":21},140,[24],"The purpose of this study is to investigate if the study medicine, KL1333, is safe, well-tolerated and effective long-term in improving the symptoms of fatigue and impacts on daily living and functional capacity (physical abilities) in people with PMD.",[60],"Mitochondrial Diseases","NOT_YET_RECRUITING","2026-03-31",{"date":64,"type":38},"2026-04-07",{"date":66,"type":21},"2026-06-09",{"date":68,"type":21},"2029-03-31",{"name":44,"class":45},{"id":71,"slug":72,"hasResults":11,"nctId":73,"briefTitle":74,"officialTitle":75,"acronym":4,"eligibilityCriteria":76,"healthyVolunteers":11,"sex":17,"minAge":77,"maxAge":78,"enrollmentInfo":79,"targetDuration":4,"studyType":22,"phases":81,"briefSummary":82,"conditions":83,"keywords":4,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":85,"lastUpdatePostDateStruct":86,"startDateStruct":88,"completionDateStruct":90,"leadSponsor":92,"locationsCount":93},"100592215","phase-2-long-term-safety-and-efficacy-of-leniolisib-in-pids-with-immune-dysregulation-100592215","NCT06990529","Long-term Safety and Efficacy of Leniolisib in PIDs With Immune Dysregulation","An Open-label, Single-arm Extension Study to Evaluate the Long-term Safety, Tolerability, and Efficacy of Leniolisib for Immune Dysregulation in Primary Immunodeficiency Disorders","Inclusion Criteria:\n\n1. Subject must have participated in LE 7201.\n2. Subject is deemed by the Investigator to benefit from continued leniolisib therapy.\n3. Subject or their legal representatives (for a patient under the age of 18 years) must be able to communicate with the Investigator and understand and comply with the requirements of the study, including an ability to provide written informed consent before any assessment is performed.\n\nExclusion Criteria:\n\n1. Subject has had a successful allogeneic hematopoietic stem cell transplant.\n2. Previous or concurrent use of immunosuppressive medication, such as:\n\n   1. Use of an mTOR inhibitor or a PI3K delta inhibitor, besides leniolisib, within 3 weeks prior to first dosing of study medication.\n   2. Rituximab or other B-cell depleting antibodies, belimumab, cyclophosphamide, or alemtuzumab within 6 months prior to first dosing of study medication.\n   3. Cyclosporine A, mycophenolate mofetil, 6-mercaptopurine, azathioprine, methotrexate, tacrolimus, ruxolitinib or other Janus kinase (JAK) inhibitors within 3 weeks prior to first dosing of study medication.\n   4. Corticosteroids above 25 mg prednisone or equivalent per day within 2 weeks prior to first dosing of study medication.\n   5. Other immunosuppressive agents expected to have a significant impact on immune cell number or function.\n3. Subject is receiving concurrent treatment with another investigational therapy or use of another investigational therapy less than 4 weeks or 5 half lives (whichever is longer) prior to first dosing of study medication.\n4. History of hypersensitivity to the study drug or to drugs of similar chemical classes.\n5. Current use of medication known to be a strong inhibitor or moderate or strong inducer, of isoenzyme cytochrome P450 (CYP)3A.\n6. Current use of medications that to a larger extent are breast cancer resistant protein (BCRP), organic anion transporting polypeptide (OATP)1B1, and\u002For OATP1B3 substrates.\n7. History of acquired immunodeficiency diseases, including a positive human immunodeficiency virus (HIV) test result at screening.\n8. Uncontrolled chronic or recurrent infectious disease (except those considered to be characteristic of PID), or evidence of tuberculosis (TB) infection as defined by a positive QuantiFERON TB-Gold test at Screening.\n9. Any surgical or medical condition which may jeopardize the subject in case of participation in the study, or might significantly alter the absorption, distribution, metabolism, or excretion of drugs (conditions due to underlying clinical PID phenotype may be permitted):\n\n   1. Uncontrolled hypertension\n   2. Congestive heart failure (New York Heart Association status of class III or IV)\n   3. Diagnosis of electrocardiogram (ECG) abnormalities indicating a significant risk of safety\n   4. Chronic obstructive pulmonary disease (Global Initiative for Chronic Obstructive Lung Disease \\[GOLD\\] stage 3-4)\n   5. Chronic need for supplemental oxygen or invasive or non-invasive respiratory support\n   6. Major GI tract surgery that may affect drug absorption (such as gastric bypass surgery, gastroenterostomy)\n   7. Acute pancreatitis\n   8. Liver failure or clinically significant liver disease or dysfunction as indicated by ALT or AST greater than 2.5 times the upper limit of normal, bilirubin greater than 2 times the upper limit of normal, INR greater than 1.5 in the absence of anticoagulation, or presence of diuretic refractory ascites\n   9. History of significant renal injury\u002Frenal disease severely affecting renal function or presence of impaired renal function as indicated by estimated glomerular filtration rate (eGFR) of less than 30 mL\u002Fmin\u002F1.73 m2.\n10. A positive hepatitis B surface antigen (HBsAg), positive hepatitis B polymerase chain reaction (PCR), positive hepatitis C PCR, or positive hepatitis C antibody result at screening.\n11. Administration of live vaccines (this includes any attenuated live vaccines) starting from 6 weeks prior to first dosing of study medication, during the study, and up to 7 days after the last dose of leniolisib.\n12. Subject has a previous diagnosis of lymphoma that has been treated with chemotherapy, radiotherapy, or transplant within 1 year prior to first dosing of study medication or is anticipated to require lymphoma treatment within 6 months of the first dose of study medication.\n13. Subject has a history of malignancy (except lymphoma) within 3 years prior to first dosing of study medication or has evidence of residual disease from a previously diagnosed malignancy, except for adequately treated cancers of the skin (basal or squamous cell) or carcinoma in situ of the uterine cervix.\n14. Subject has uncontrolled post-transplant lymphoproliferative disease-like Epstein-Barr-virus-related lymphoproliferative disease.\n15. Subject has had major surgery requiring hospitalization or radiotherapy within 4 weeks prior to first dosing of study medication or has a planned or expected major surgical procedure during the study period.\n16. Pregnant or nursing (lactating) women.\n17. An individual of child-bearing potential who is physiologically capable of becoming pregnant, unless using highly effective methods of contraception.","12 Years","75 Years",{"count":80,"type":21},12,[24],"This is an open-label extension (OLE) study to extend treatment to patients with primary immunodeficiency (PID) disorders linked to phosphoinositide 3-kinase delta signaling who participated in a prior study of leniolisib, LE 7201. The primary objective is to assess long-term safety and tolerability of leniolisib. Secondary and exploratory objectives include various efficacy and immunophenotyping measures for leniolisib.",[84],"PIDs Linked to PI3K","2026-02-10",{"date":87,"type":38},"2026-02-13",{"date":89,"type":38},"2025-04-29",{"date":91,"type":21},"2029-04-13",{"name":44,"class":45},4,""]