A Study to Evaluate ASP0367 in Participants With Primary Mitochondrial Myopathy (MOUNTAINSIDE)

Overview

About this study

The purpose of this study is to evaluate the effectiveness, safety and tolerability of ASP0367 in participants with Primary Mitochondrial Myopathy (PMM).

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written informed consent and privacy language as per national regulations (e.g., Health Insurance Portability and Accountability Act authorization for US study sites) must be obtained from the participant prior to any study-related procedures (including withdrawal of prohibited medication, if applicable).
  • 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.
  • Participant is ≥ 18 and ≤ 80 years of age at the time of signing an informed consent form (ICF).
  • Diagnosed with PMM in the opinion of the investigator, 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, mtDNA single, variable deletions in CPEO and KSS; mtDNA m.3243 A > G common mutation in 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);
    • OCBP 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, in the opinion of the investigator.

Exclusion Criteria:

  • 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), in the opinion of the investigator.
  • Participant has received any investigational therapy within 28 days or 5 half-lives, whichever is longer, prior to screening.
  • Participant has any condition, which, in the investigator’s opinion, makes the participant unsuitable for study participation.
  • Participant has cTnI > ULN at screening and is assessed as clinically significant by the investigator.
  • 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 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, as assessed by the investigator at screening.
  • Participant has severe behavioral or cognitive problems that preclude participation in the study, in the opinion of the investigator.
  • Participant has undergone an in-patient hospitalization that precludes participation in the study, in the opinion of the investigator, 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 in the opinion of the investigator.
  • Participant has clinically significant and unstable respiratory disease and/or cardiac disease (medical history or current clinical findings) in the opinion of the investigator, 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 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, in the opinion of the investigator, may interfere with their ability to complete all study requirements.
  • Participant has an intractable seizure disorder that, in the opinion of the investigator, 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 whom 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, in the opinion of the investigator, a history of active substance abuse within 1 year prior to randomization.
  • Participant has used any 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.       

Eligibility last updated 5/18/22. Questions regarding updates should be directed to the study team contact.                                                                                                                                                                                                                                                                                                                                                                   

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Ralitza Gavrilova, M.D.

Closed-enrolling by invitation

What is this? (?)
"Close"
Not open to everyone who meets the eligibility criteria, but only those invited to participate by the study team.

Contact information:

Danielle Bostrom

(507) 422-5380

Bostrom.Danielle@mayo.edu

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Radhika Dhamija, M.B.B.S.

Closed-enrolling by invitation

What is this? (?)
"Close"
Not open to everyone who meets the eligibility criteria, but only those invited to participate by the study team.

Contact information:

Aatikah Mouti

(480) 342-2479

Mouti.Aatikah@mayo.edu

Jacksonville, Fla.

Mayo Clinic principal investigator

Klaas Wierenga, M.D.

Closed-enrolling by invitation

What is this? (?)
"Close"
Not open to everyone who meets the eligibility criteria, but only those invited to participate by the study team.

Contact information:

Clinical Studies Unit

(904) 953-2255

More information

Publications

Publications are currently not available
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CLS-20521243

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