A Phase III, Randomised, Double-blind, Placebo-controlled, Parallel-group, Pivotal Trial to Assess the Efficacy and Safety of Sonlicromanol in Adult Subjects With a Genetically Confirmed Mitochondrial DNA tRNALeu(UUR) m.3243A>G Variant

The KHENERFIN study is investigating whether the study medicine, sonlicromanol, is able to improve symptoms of fatigue and the impact of fatigue on daily life, and whether sonlicromanol is able improve physical abilities of people living with mitochondrial disease, such as balance control and lower limb skeletal muscle strength.
For this study, the effects of sonlicromanol are compared with those from a placebo (study medication that looks like the actual study medicine but contains no active medicine). The study medicine (or placebo) is a powder that is dissolved in water and must be taken twice daily during the treatment period of 52 weeks.
Additionally, the study evaluates the efficacy of sonlicromanol on selected secondary and exploratory outcome measures, as well as the safety and tolerability of sonlicromanol after 52 weeks of treatment with sonlicromanol.

开始日期2025-01-02

申办/合作机构

Khondrion BV

NCT06644534 / Not yet recruiting临床2期

A Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Oral TTI-0102 for Treatment of Patients With Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-like Episodes (MELAS)

This is a randomized, double-blind, placebo-controlled study. Prior to treatment, patients will undergo a screening visit. If eligible, each subject will return for a Day 1 visit and will receive their first dose of investigational product (TTI-0102 or placebo). At the end of the first week of treatment, subjects will return for a Week 1/Day 8 study visit to assess study drug dosing/tolerance and instruct on dosing for the upcoming second week of treatment.
For the first 8 weeks of treatment, subjects will alternate between returning to the clinic for detailed assessments (Weeks 4 and 8) and receiving a telephone call from the Investigator team to assess safety and TTI-0102 dose (Weeks 2 and 6) and the potential need for an immediate unscheduled study visit.
After the first 8 weeks of treatment, subjects will continue to return to the clinic for monthly assessments at Weeks 12, 16, 20. The Study Exit visit will occur at Week 24, and subjects will be offered to continue on an open-label extension study of TTI-0102. If a subject does not complete the study, they will be asked to return for a Study Exit visit 4 weeks after last study drug dose.
Primary Objective The primary objective of this study is to assess the efficacy, safety and tolerability of oral TTI 0102 compared to placebo, for up to 6 months in patients with MELAS.
Secondary Objective The secondary objectives of this study are to assess the efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) of cysteamine after oral administration of TTI-0102 at steady state, in patients with MELAS on a stable dose of TTI-0102.
This is a randomized, double-blind, placebo-controlled study. Prior to treatment, patients will undergo a screening visit. If eligible, each subject will return for a Day 1 visit and will receive their first dose of investigational product (TTI-0102 or placebo). At the end of the first week of treatment, subjects will return for a Week 1/Day 8 study visit to assess study drug dosing/tolerance and instruct on dosing for the upcoming second week of treatment.
For the first 8 weeks of treatment, subjects will alternate between returning to the clinic for detailed assessments (Weeks 4 and 8) and receiving a telephone call from the Investigator team to assess safety and TTI-0102 dose (Weeks 2 and 6) and the potential need for an immediate unscheduled study visit.
After the first 8 weeks of treatment, subjects will continue to return to the clinic for monthly assessments at Weeks 12, 16, 20. The Study Exit visit will occur at Week 24, and subjects will be offered to continue on an open-label extension study of TTI-0102. If a subject does not complete the study, they will be asked to return for a Study Exit visit 4 weeks after last study drug dose.
Study Drug Dosing To prevent any manifestation of intolerance at the initiation of drug treatment, only half a dose (2.75 grams) will be given once a day for the first week of treatment. During the following weeks of treatment, patients will be given a full dose of 5.5 grams once a day.
Interim Data Review After nine (9) patients have completed three months of treatment (the Week 12 visit) an interim data cut will take place to assess safety and potential efficacy signals. Even if no indications of efficacy are detected at this early stage, the trial itself will not be terminated unless there is a serious safety concern (i.e., protocol-defined Stopping Criteria are met).

开始日期2024-11-30

申办/合作机构

Thiogenesis Therapeutics, Inc.

NCT06080594 / RecruitingN/AIIT

Exercise-mediated Rescue of Mitochondrial Derangements Driving Insulin Resistance in Humans (EX-MITO-DYS-IR)

The overarching aim of this intervention study is to interrogate the interconnection between the muscle mitochondrial adaptations and the changes in muscle insulin sensitivity elicited by exercise training in individuals harbouring pathogenic mitochondrial DNA mutations associated with an insulin-resistant phenotype.
In a within-subject parallel-group longitudinal design, participants will undergo an exercise training intervention with one leg, while the contralateral leg will serve as an inactive control. After the exercise intervention, patients will attend an experimental trial including:
* A hyperinsulinemic-euglycemic clamp combined with measurements of femoral artery blood flow and arteriovenous difference of glucose
* Muscle biopsy samples

开始日期2024-09-22

申办/合作机构

Rigshospitalet

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100 项与线粒体肌病相关的临床结果

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100 项与线粒体肌病相关的转化医学

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0 项与线粒体肌病相关的专利（医药）

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9,481

项与线粒体肌病相关的文献（医药）

2025-02-01·Current Pediatric Reviews

A Case Series of Appendicitis and Pseudo-appendicitis in a Paediatric Intensive Care Unit

Review

作者: Leung, Wai Y.M. ; Lee, Yan T.K. ; Cheung, Wing L. ; Hon, Kam L. ; Tsang, Stephanie ; Leung, Karen K.Y. ; Leung, Alexander K.C. ; Hui, Wun F.A.

Introduction:Appendicitis is a common childhood condition that can be diagnostically challenging. Severe cases may necessitate support in the critical or intensive care unit. These “criti-cal appendicitis diagnoses” have rarely been described.Case Description:We retrospectively reviewed the Paediatric Intensive Care Unit (PICU) database of the Hong Kong Children’s Hospital and identified cases of suspected and confirmed appendicitis. Clinical features, radiologic findings and final diagnosis of each case were summarized and report-ed in this case series. We review six anonymized cases of appendicitis managed in a PICU to illus-trate the different age spectrum and clinical manifestations of the condition. Rupture of the inflamed appendix, peritonitis and pancreatitis were some of the complications encountered. Crohn’s disease was found in one case as an underlying diagnosis. Also, one girl clinically diagnosed with appendi-citis was found to be a case of ruptured hepatoblastoma with no appendicitis (i.e., pseudo-appendicitis).Conclusion:Prompt diagnosis, surgical removal of the inflamed appendix, and use of appropriate antimicrobials when indicated are essential in reducing mortality and morbidity associated with se-vere appendicitis. Significant premorbid conditions such as acute myeloid leukemia, Mitochondrial Encephalopathy Lactic Acidosis Syndrome (MELAS), inflammatory bowel disease and complica-tions may be present in patients needing intensive care as is illustrated in the present cases. Pseudo-appendicitis is an important differential diagnosis. Imaging is crucial and useful in establishing and confirming the diagnosis of appendicitis and pseudo-appendicitis in these PICU cases.

2025-01-01·Journal of Affective Disorders

Clinical features of obsessive-compulsive disorder among individuals who experience health-related obsessive-compulsive symptoms

Article

作者: Fontenelle, Leonardo F. ; Brierley, Mary-Ellen E. ; Albertella, Lucy ; Nanthakumar, Sandhiya ; Brierley, Mary-Ellen E ; Fontenelle, Leonardo F ; do Rosário, Maria Conceição

BACKGROUNDWhile some obsessive-compulsive disorder (OCD) phenotypes are well-established and better understood, it is unclear whether the presence of health-related obsessive-compulsive symptoms (OCS) is associated with specific clinical characteristics. We aimed to investigate whether OCS involving concerns with illness, diseases, body parts or aspects of appearance (i.e. health-related OCS) are associated with differences in demographics, experience of stressful life events, clinical severity, clinical course, endorsement of established OCD dimensions, and psychiatric comorbidities.METHODSIndividuals (N = 1001) with a clinical diagnosis of OCD (M = 34.85, SD = 12.99) completed a questionnaire battery assessing clinical course (age at symptom onset, age at diagnosis, duration of illness), total and dimensional symptom severity, and psychiatric comorbidities. We ran initial univariate, and follow-up multivariate analyses where appropriate, to compare individuals reporting health-related OCS with those not reporting health-related OCS in terms of demographics, symptom severity and clinical course, OCD symptom dimensions, and psychiatric comorbidities.RESULTSThe presence of health-related OCS was associated with higher severity of contamination, hoarding and harm symptoms. Additionally, those with health-related OCS displayed significantly lower symptom insight, increased incidence of hypochondriasis, panic disorder and anxiety, and lower depression symptoms. Overall OCD symptom severity and clinical course did not differ between participants with and without health-related OCS.IMPLICATIONSThese novel findings provide clinicians with an enhanced understanding of health-related OCS in order to guide assessment and allow for more targeted treatment planning. Future investigations may examine the effectiveness of specialised treatment methods which target underlying clinical features of health-related OCS.

2024-12-31·Renal Failure

Obeticholic acid ameliorates sepsis-induced renal mitochondrial damage by inhibiting the NF-κb signaling pathway

Article

作者: Li, Yu ; Lin, Jin ; Li, Tian ; Jing, Danyang ; Liu, Jingfeng ; Qin, Da ; Duan, Meili

Acute kidney injury (AKI), a common complication of sepsis, might be caused by overactivated inflammation, mitochondrial damage, and oxidative stress. However, the mechanisms underlying sepsis-induced AKI (SAKI) have not been fully elucidated, and there is a lack of effective therapies for AKI. To this end, this study aimed to investigate whether obeticholic acid (OCA) has a renoprotective effect on SAKI and to explore its mechanism of action. Through bioinformatics analysis, our study confirmed that the mitochondria might be a critical target for the treatment of SAKI. Thus, a septic rat model was established by cecal ligation puncture (CLP) surgery. Our results showed an evoked inflammatory response via the NF-κB signaling pathway and NLRP3 inflammasome activation in septic rats, which led to mitochondrial damage and oxidative stress. OCA, an Farnesoid X Receptor (FXR) agonist, has shown anti-inflammatory effects in numerous studies. However, the effects of OCA on SAKI remain unclear. In this study, we revealed that pretreatment with OCA can inhibit the inflammatory response by reducing the synthesis of proinflammatory factors (such as IL-1β and NLRP3) via blocking NF-κB and alleviating mitochondrial damage and oxidative stress in the septic rat model. Overall, this study provides insight into the excessive inflammation-induced SAKI caused by mitochondrial damage and evidence for the potential use of OCA in SAKI treatment.

169

项与线粒体肌病相关的新闻（医药）

2024-10-15

·PMLiVE

FDA advisory committee recommends Stealth’s elamipretide for Barth syndrome

A US Food and Drug Administration (FDA) panel of experts has voted in support of Stealth BioTherapeutics’ elamipretide for Barth syndrome, an ultra-rare genetic disease that affects approximately 150 people in the US. There are currently no therapies approved by the regulator for Barth syndrome, which primarily occurs in males and is characterised by cardiac abnormalities. The disease leads to muscle weakness, exercise intolerance, fatigue, heart failure, recurrent infections and delayed growth, and is associated with a reduced life expectancy. The Cardiovascular and Renal Drugs Advisory Committee (CRDAC) voted ten to six in favour of Stealth’s application for elamipretide, concluding that the drug is effective for this patient population. Among the evidence supporting the committee’s decision was positive results from the TAZPOWER part two baseline-controlled extension study, the late-stage SPIBA-001 natural history control study, as well as supportive biomarker and preclinical data. Stealth’s chief executive officer, Reenie McCarthy, said: “We are pleased that the FDA advisory committee has thoughtfully considered the elamipretide data package… and recognised that this data supports the potential of elamipretide to improve the lives of patients with this devastating disease.” The CRDAC’s vote will now be considered by the FDA as it completes its independent review of elamipretide in this indication, with a final decision expected in January 2025. Elamipretide has already been granted orphan drug, fast track and rare paediatric disease designations by the FDA, as well as orphan drug designation by the European Medicines Agency for Barth syndrome. The drug is also being evaluated in late-stage trials for primary mitochondrial myopathy and dry age-related macular degeneration. Beyond elamipretide, Stealth is evaluating a topical ophthalmic formulation of its clinical-stage candidate bevemipretide for dry age-related macular degeneration, and has a pipeline of compounds under evaluation for rare neurological and cardiac disease indications. The vote on elamipretide comes just one month after the company was awarded a grant from the Friedreich’s Ataxia (FA) Research Alliance to evaluate its mitochondria-targeted molecule SBT-589 in FA, an inherited disease that causes progressive damage to the nervous system and estimated to affect one in 50,000 individuals in the US.

孤儿药快速通道临床结果

2024-10-11

·药明康德

10：6！创新疗法获FDA咨询委员会支持用以治疗这项无药可医的疾病

▎药明康德内容团队编辑 Stealth BioTherapeutics今天宣布，美国FDA心血管和肾脏药物咨询委员会（CRDAC）以10比6的票数支持该公司在研疗法elamipretide用于治疗巴思综合征（Barth syndrome）患者。该疗法的新药申请（NDA）已获得优先审评资格，FDA预计在2025年1月29日以前公布审评结果。如果获得批准，elamipretide将成为巴思综合征的首款获批疗法。 CRDAC讨论了elamipretide用于治疗巴思综合征的益处和风险，包括TAZPOWER试验第2部分基线对照扩展研究的结果、SPIBA-001临床3期试验自然史对照研究的结果，以及其他支持性生物标志物和临床前数据。CRDAC的投票虽然不具约束力，但美国FDA在就elamipretide治疗巴思综合征做出潜在批准决定时会考虑该投票结果。巴思综合征是一种危及生命、极为罕见的遗传性线粒体疾病，其特征是患者的心脏异常，导致其运动不耐受、肌肉无力、虚弱性疲劳、心力衰竭、反复感染和生长迟缓。患者的的预期寿命通常较短，85%患者的死亡发生在5岁之前。巴思综合征主要发生在男性身上，据估计，全球每1百万名男性中有1人患有该病。目前尚无美国FDA或欧洲药品管理局（EMA）批准针对巴思综合征患者的疗法。 Elamipretide是一种肽化合物，可轻易穿透细胞膜，靶向线粒体内膜，并可逆性地与心磷脂（cardiolipin）结合。在临床前或临床研究中观察到该疗法可增加线粒体呼吸作用、改善电子递送链功能和ATP生成，并减少致病性活性氧（ROS）的形成。这种elamipretide-心磷脂结合已被证明可以使线粒体内膜结构正常化，从而改善线粒体功能。除了正在接受用以治疗巴思综合征的审评外，该疗法还处于治疗原发性线粒体肌病和干性年龄相关性黄斑变性的后期开发阶段。Elamipretide已获得美国FDA授予孤儿药资格、快速通道资格和罕见儿科疾病认定，以及EMA的孤儿药资格，用于治疗巴思综合征。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料： [1] Stealth BioTherapeutics Announces Positive Vote from FDA Advisory Committee Meeting Supporting Potential Approval of Elamipretide for the Treatment of Barth Syndrome. Retrieved October 11, 2024 from https://stealthbt.com/stealth-biotherapeutics-announces-positive-vote-from-fda-advisory-committee-meeting-supporting-potential-approval-of-elamipretide-for-the-treatment-of-barth-syndrome/ [2] Programs & Pipeline. Retrieved October 11, 2024 from https://stealthbt.com/programs-pipeline/#pipeline 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

优先审批孤儿药快速通道临床3期

2024-10-11

·PRNewswire

Stealth BioTherapeutics Announces Positive Vote from FDA Advisory Committee Meeting Supporting Potential Approval of Elamipretide for the Treatment of Barth Syndrome

Advisory Committee Voted 10 to 6 in Favor, Concluding that Elamipretide is Effective for the Treatment of Barth Syndrome Elamipretide NDA Received Priority Review with a PDUFA Action Date of January 29, 2025 If Approved, Elamipretide Would Be the First Therapy for Barth Syndrome, a Life-Threatening Ultra-Rare Mitochondrial Disease NEEDHAM, Mass., Oct. 11, 2024 /PRNewswire/ -- Stealth BioTherapeutics Inc. (the "Company" or "Stealth"), a clinical-stage biotechnology company focused on the discovery, development and commercialization of novel therapies for diseases involving mitochondrial dysfunction, today announced that the U.S. Food and Drug Administration ("FDA") Cardiovascular and Renal Drugs Advisory Committee ("CRDAC") voted 10 to 6 in favor of Stealth's New Drug Application ("NDA"), concluding that elamipretide is effective for the treatment of patients with Barth syndrome. The CRDAC discussed the benefits and risks of elamipretide for the treatment of Barth syndrome, including results from the TAZPOWER Part 2 baseline-controlled extension study, the SPIBA-001 Phase 3 natural history control study, and additional supportive biomarker and preclinical data. The CRDAC's vote, while not binding, will be considered by the FDA when making its decision regarding the potential approval of elamipretide for Barth syndrome. If approved, elamipretide would be the first therapy for this ultra-rare, progressive, life-shortening, cardioskeletal disease that affects approximately 150 individuals in the United States. The NDA for elamipretide was granted priority review and has been assigned a Prescription Drug User Fee Act ("PDUFA") action date of January 29, 2025. "We are pleased that the FDA advisory committee has thoughtfully considered the elamipretide data package – including the positive results from the rigorously constructed natural history control trial, the durable open-label extension data, and expanded access cases – and recognized that these data support the potential of elamipretide to improve the lives of patients with this devastating disease," said Reenie McCarthy, Chief Executive Officer. "We are grateful to the many patients, caregivers, advocates, and healthcare providers who shared their perspectives and experiences with the advisory committee. We look forward to collaborative conversations with the FDA as the agency completes its review of elamipretide, the first potential therapy for Barth syndrome." If approved, this would be the first marketing authorization for elamipretide, a first-in-class mitochondria-targeted therapeutic. In addition to Barth syndrome, elamipretide is in Phase 3 trials for primary mitochondrial myopathy, with pivotal data expected by the end of 2024, and for dry age-related macular degeneration. About Barth Syndrome Barth syndrome is an ultra-rare genetic condition characterized by cardiac abnormalities leading to exercise intolerance, muscle weakness, debilitating fatigue, heart failure, recurrent infections, and delayed growth. The disease is associated with reduced life expectancy, with 85% of early deaths occurring by age 5. Barth syndrome occurs primarily in males and is estimated to affect one in 1,000,000 males worldwide or around 150 individuals in the United States. There are currently no FDA- or EMA-approved therapies for patients with Barth syndrome. Elamipretide has Orphan Drug, Fast Track and Rare Pediatric Designation from the FDA and Orphan Drug Designation from the EMA for the treatment of Barth syndrome. About Stealth BioTherapeutics Our mission is to develop novel therapies to improve the lives of patients living with diseases of mitochondrial dysfunction. Our lead product candidate, elamipretide, is under review for Barth syndrome and in late-stage development for primary mitochondrial myopathy and dry age-related macular degeneration. We are also evaluating a topical ophthalmic formulation of our second-generation clinical-stage candidate, bevemipretide (SBT-272), for dry age-related macular degeneration, and have a deep pipeline of novel compounds under evaluation for rare neurological and cardiac disease indications. Media Contact Anna Stallmann Communications Anna Stallmann [email protected] Investor Contact Precision AQ Austin Murtagh [email protected] SOURCE Stealth BioTherapeutics Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED