A Study to Evaluate ASP0367 in Participants With Primary Mitochondrial Myopathy
The purpose of the phase 2 portion of this study is to select a biologically-active ASP0367 dose level by pharmacokinetic (PK) and pharmacodynamic (PD) evaluation. The phase 2 portion of this study will also assess the safety and tolerability of ASP0367. The purpose of the phase 3 portion of this study is to assess the effect of ASP0367 on functional improvement relative to placebo and will also assess the safety and tolerability of ASP0367 relative to placebo. The phase 3 portion of this study will also assess the effect of ASP0367 on functional improvement and fatigue relative to placebo and will assess the effect of ASP0367 in overall participant functioning relative to placebo.
- Primary Mitochondrial Myopathy
- Eligible Ages
- Between 18 Years and 80 Years
- Eligible Genders
- Accepts Healthy Volunteers
- Participant agrees and is able to adhere to the study requirements for the length of the study, including performing 6MWT, as well as the use of digital applications and video recordings. - Diagnosed with primary mitochondrial myopathy (PMM), consisting of the following: - Molecular genetic abnormality (i.e., nuclear or mitochondrial) known to be associated with causing mitochondrial dysfunction (such as, but not limited to, mitochondrial DNA (mtDNA) single, variable deletions in chronic progressive external ophthalmoplegia (CPEO) and Kearns-Sayre syndrome (KSS); mtDNA m.3243 A > G common mutation in mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS); pathogenic nuclear or mitochondrial genome variants demonstrated to cause primary mitochondrial disease), and - Participant reported symptoms (i.e., muscle weakness, fatigue and exercise intolerance) or physical examination findings of myopathy that are the predominant symptoms of the participant's mitochondrial disorder. - Participant has been on stable dose regimen of coenzyme Q10 (CoQ10), carnitine, creatine or other mitochondrial disease-focused vitamins or supplemental therapies for 3 months prior to randomization and intends to stay on a stable dose for duration of study period (for participants who take any above-mentioned medications or supplements). - Participant has been on stable exercise regimen within 4 weeks prior to randomization and intends to stay on a stable regimen for duration of study period (for participants who participate in a regular exercise regimen). - Female participant is not pregnant and at least one of the following conditions apply: - Not a woman of childbearing potential (WOCBP). - WOCBP who agrees to follow the contraceptive guidance from the time of informed consent through at least 30 days after final study treatment administration. - Female participant must agree not to breastfeed starting at screening and throughout the study period and for 30 days after final study treatment administration. - Female participant must not donate ova starting at first dose of IP and throughout the study period and for 30 days after final study treatment administration. - Male participant with female partner(s) of childbearing potential (including breastfeeding partner) must agree to use contraception throughout the treatment period and for 30 days after final study treatment administration. - Male participant must not donate sperm during the treatment period and for 30 days after final study treatment administration. - Male participant with pregnant partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy throughout the study period and for 30 days after final study treatment administration. - Participant agrees not to participate in another interventional study while participating in the present study. Open-label Extension Continuation Criteria: - Participant must meet all of the following OLE criteria at the week 52 study visit in the treatment period to be eligible for OLE: - Participant must continue to be able and willing to adhere to the study requirements. - Participant who is eligible to continue in OLE.
- Participant has additional signs and/or symptoms due to non-myopathic process (e.g., cerebellar dysfunctions, movement disorder, peripheral neuropathy, stroke or other) or a gait problem not attributed to the myopathy that would interfere/may in addition to the myopathy affect the participant's performance during 6MWT or 5 times sit to stand (5XSTS). - Participant has received any investigational therapy within 28 days or 5 half-lives, whichever is longer, prior to screening. - Participant has any condition, which makes the participant unsuitable for study participation. - Participant has cardiac troponin I (cTnI) > upper limit of normal (ULN) at screening and is assessed as clinically significant. - Participant has estimated glomerular filtration rate (eGFR) calculated by the Modification of Diet in Renal Disease equation < 60 mL/min/1.73 m^2 at screening. - Participant has at screening: total bilirubin (TBL) > ULN or transaminase(s) (aspartate aminotransferase [AST] or alanine aminotransferase [ALT]) > ULN in the absence of elevations in creatine kinase (CK). - Participant has psychiatric conditions such as schizophrenia, bipolar disorder or major depressive disorder that has not been under control within 3 months prior to screening. - Participant has a history of suicide attempt, suicidal behavior or has any suicidal ideation within 1 year prior to screening that meets criteria at a level of 4 or 5 by using the Columbia-Suicide Severity Rating Scale (C-SSRS) or who is at significant risk to commit suicide. - Participant has severe behavioral or cognitive problems that preclude participation in the study. - Participant has undergone an in-patient hospitalization that precludes participation in the study, within the 30 days prior to the randomization. - Participant has a planned hospitalization or a surgical procedure during the study, which may affect the study assessments. - Participant has clinically significant and unstable respiratory disease and/or cardiac disease (medical history or current clinical findings), or prior interventional cardiac procedure (e.g., cardiac catheterization, angioplasty/percutaneous coronary intervention, balloon valvuloplasty, etc.) within 3 months prior to randomization. - Participant has a corrected mean QT interval using Fridericia's correction (QTcF) > 450 msec for male participants and > 480 msec for female participants at screening or randomization. If QTcF exceeds these limits, one additional triplicate ECG can be repeated on the same day in order to determine the participant's eligibility. - ECG evidence of acute ischemia, atrial fibrillation or active conduction system abnormalities with the exception of any of the following: - First degree atrioventricular (AV)-block - Second degree AV-block Type 1 (Mobitz Type 1/Wenckebach type) - Right bundle branch block - Left fascicular block - Bi-fascicular block - Participant requires 24/7 ventilator support (those who require nocturnal ventilation support such continuous positive airway pressure [CPAP] or bilevel positive airway pressure [BiPAP], due to nighttime hypoxia from chest muscle weakness or obstructive sleep apnea are allowed). - Participant has severe vision impairment that may interfere with their ability to complete all study requirements. - Participant has an intractable seizure disorder that may interfere with their ability to complete all study requirements. - Active malignancy or any other cancer from which the participant has been disease-free for < 5 years, except for curative treated localized non-melanoma skin cancer (e.g., basal cell or squamous cell carcinoma). - Participant has a solid organ transplant and/or is currently receiving treatment with therapy for immunosuppression. - Participant has severe scoliosis or kyphoscoliosis that significantly impair respiratory capacity and pulmonary function tests or limit positioning due to pain who would be likely to require orthopedic surgical intervention within a year after study randomization. - Participant has a positive for human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection at screening. - Participant has previously received ASP0367. - Participant has a history of active substance abuse within 1 year prior to randomization. - Participant has used any peroxisome proliferator-activated receptor (PPAR) ligands such as fibrates and thiazolidinediones within 4 weeks prior to randomization. - Participant has initiated the use of CoQ10, carnitine, creatine or other mitochondrial disease-focused supplements within 3 months prior to study randomization. - Participant has a known or suspected hypersensitivity to ASP0367 or any components of the formulation used.
- Phase 2/Phase 3
- Study Type
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Triple (Participant, Care Provider, Investigator)
- Masking Description
- Phase 2/3 masking: Subject, Caregiver, Investigator Open-label extension: No masking
Phase 2: low dose ASP0367
|Participants will receive ASP0367 once daily in the morning for 2 weeks.||
Phase 2: high dose ASP0367
|Participants will receive ASP0367 once daily in the morning for 2 weeks.||
Phase 2: Placebo
|Participants will receive placebo once daily in the morning for 2 weeks.||
Phase 3: ASP0367
|Participants will receive ASP0367 once daily in the morning for up to 52 weeks.||
Phase 3: Placebo
|Participants will receive placebo once daily in the morning for up to 52 weeks.||
Open Label Extension: ASP0367
|Participants will receive ASP0367 once daily in the morning for 24 weeks.||
- Astellas Pharma Inc
Study ContactAstellas Pharma Inc.
Efficacy (i.e., functional improvement) will be assessed by a functional motor test, 6-minute walk test (6MWT). The study consists of the following portions: screening (4 weeks); phase 2 dose selection portion with 2 doses of ASP0367 versus matching placebo (2 weeks); phase 3 portion with selected, single dose treatment versus placebo (up to 52 weeks); open-label extension (OLE) (24 weeks); and follow-up (4 weeks). During the phase 2 portion of the study, participants will be randomly placed into 1 of 3 arms (low dose ASP0367, high dose ASP0367 or placebo). The relevant dose level will be selected based on the pharmacokinetics/pharmacodynamics and overall safety. Participants will maintain their original Phase 2 dose level and no new participants will be enrolled in the study until phase 3 dose selection is made. After the phase 3 dose is selected, all participants except the placebo group will switch to the selected dose level of ASP0367 for the remainder of the phase 3 portion of the study (up to a total 52 weeks including the phase 2 portion). Participants who were originally assigned to placebo will remain on placebo for up to 52 weeks. The remaining enrollment of participants will be randomized to either ASP0367 or matching placebo at a ratio of 1:1. All participants who have completed the phase 3 portion of the study and are eligible for the OLE will be offered the opportunity to take ASP0367 for an additional 24 weeks.