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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT04641962
Other study ID # 0367-CL-1201
Secondary ID
Status Terminated
Phase Phase 2
First received
Last updated
Start date May 17, 2021
Est. completion date May 8, 2024

Study information

Verified date June 2024
Source Astellas Pharma Inc
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the dose response of ASP0367 on functional improvement relative to placebo, safety, and tolerability in participants with Primary Mitochondrial Myopathy.


Description:

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); double-blind treatment period with 2 doses of ASP0367 vs matching placebo (24 weeks) and follow up (4 weeks). Participants will be randomly placed into 1 of 3 arms (low dose ASP0367, high dose ASP0367 or placebo).


Recruitment information / eligibility

Status Terminated
Enrollment 34
Est. completion date May 8, 2024
Est. primary completion date April 9, 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years to 65 Years
Eligibility Inclusion Criteria: - Participant agrees and is able to adhere to the study requirements for the length of the study, including performing 6MWT. - Diagnosed with primary mitochondrial myopathy (PMM), consisting of the following: - Molecular genetic abnormality (i.e., nuclear or mitochondrial) known to be associated with mitochondrial dysfunction (such as, but not limited to, mitochondrial DNA (mtDNA) single deletions in chronic progressive external ophthalmoplegia (CPEO) and Kearns-Sayre syndrome (KSS); mtDNA m.3243 A > G 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 the treatment of symptoms of the mitochondrial disease for at least 3 months prior to randomization and intends to stay on a stable dose for duration of study period. - 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. 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 with 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. - Participant has estimated glomerular filtration rate (eGFR) calculated by the chronic kidney disease epidemiology collaboration equation < 60 milliliter per minute per 1.73-meter square at screening or a history of chronic kidney disease stage 3 or greater. - 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. Participants who have a slightly elevated TBL and/or ALT and/or AST and are suitable candidates for the study may be enrolled after discussion of the case with the medical monitor and completion of further evaluation as warranted. - 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. Participants with pacemakers are allowed in the study per investigator's discretion and after discussion with the medical monitor, and as long as it is used for prevention and there is no underlying cardiac dysfunction. - 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. The following conduction system abnormalities may be permitted per the investigator's discretion, only after discussing the case with the medical monitor: - 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 any ventilatory support, inclusive of any respiratory device to support breathing such as home ventilators and any form of non-invasive positive pressure ventilation (including continuous positive airway pressure [CPAP], bilevel positive airway pressure [BiPAP], and average volume-assured pressure support [AVAPS]). Participants who require oxygen therapy (even by low flow nasal cannula [LFNC]) are not candidates for this study. - 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 test 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 for the treatment of symptoms of the mitochondrial disease within 3 months prior to study randomization. - Participant has a known or suspected hypersensitivity to ASP0367 or any components of the formulation used. - Participant has symptomatic coronavirus disease 2019 (COVID-19) infection within 3 months prior to study randomization that required treatment (Monoclonal antibodies, ventilator support, hospitalization) and/or led to long-term sequelae or lingering symptoms. - Participant has body mass index (BMI) below 17 kg/ m^2 or above 35 kg/ m^2 at screening. - Participant has signs or symptoms of bulbar weakness, such as dysphagia, dysphonia, hoarseness or drooling/sialorrhea, due to either neuropathy or myopathy.

Study Design


Intervention

Drug:
Bocidelpar
Oral
Placebo
Oral

Locations

Country Name City State
United States Akron Children's Hospital Akron Ohio
United States Children's Hospital Colorado Aurora Colorado
United States Massachusetts General Hospital Boston Massachusetts
United States Cleveland Clinic Cleveland Ohio
United States Baylor College of Medicine Houston Texas
United States University of Texas Health Science Center at Hosuton Houston Texas
United States University of California, San Diego La Jolla California
United States Columbia University Irving Medical Center New York New York
United States Children's Hospital of Philadelphia Philadelphia Pennsylvania
United States Seattle Children's Hospital Seattle Washington
United States Stanford University Medical Center Stanford California

Sponsors (1)

Lead Sponsor Collaborator
Astellas Pharma Inc

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Safety and tolerability assessed by nature, frequency and severity of treatment emergent adverse events (TEAEs) TEAE will be coded using medical dictionary for regulatory activities (MedDRA). A TEAE is defined as an adverse event (AE) observed after starting administration of the investigational product (IP) to 28 days after the last dose of IP for the double-blind treatment period of the study or moving to the OLE or day 182, whichever comes first based on the protocol version on which participants were enrolled. An AE is any untoward medical occurrence in a participant, temporally associated with the use of IP, whether or not considered related to the IP. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of IP. This includes events related to the comparator and events related to the study procedures. Through Week 24
Primary Number of participants with body weight change abnormalities and/or AEs Number of participants with potentially clinically significant body weight changes. Through Week 24
Primary Number of participants with 12-lead electrocardiogram (ECG) abnormalities and/or AEs Number of participants with potentially clinically significant 12-lead ECG values. Through Week 24
Primary Number of participants with laboratory value abnormalities and/or AEs Number of participants with potentially clinically significant laboratory values. Through Week 24
Primary Number of participants with vital sign abnormalities and/or AEs Number of participants with potentially clinically significant vital sign values. Through Week 24
Primary Number of participants with suicidal ideation and/ or behavior as assessed Columbia-Suicide Severity Rating Scale (C-SSRS) The Columbia-Suicide Severity Rating Scale (C-SSRS) is a clinician administered assessment tool that evaluates suicidal ideation and behavior. Number of participants that have an affirmative response provided to the 5 items for suicidal ideation (1. Wish to be dead, 2. Nonspecific active suicidal thoughts, 3. Active suicidal ideation with any methods (not plan) without intent to act, 4. Active suicidal ideation with some intent to act, without specific plan, 5. Active suicidal ideation with specific plan and intent) and/or to the 6 items for suicidal behavior (1. Actual attempt, 2. Interrupted attempt, 3. Aborted attempt, 4. Preparatory acts or behavior, 5. Suicidal Behavior 6. Completed suicide). Through Week 24
Primary Safety and tolerability assessed by nature, frequency and severity of treatment emergent adverse events (TEAEs) Treatment emergent adverse events will be coded using medical dictionary for regulatory activities (MedDRA). A TEAE is defined as an adverse event (AE) observed after starting administration of the investigational product (IP) to 28 days after the last dose of IP for the double-blind treatment period of the study or moving to the OLE or day 182, whichever comes first based on the protocol version on which participants were enrolled. An AE is any untoward medical occurrence in a participant, temporally associated with the use of IP, whether or not considered related to the IP. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of IP. This includes events related to the comparator and events related to the study procedures. Through Week 28 (end of study)
Primary Number of participants with body weight change abnormalities and/or AEs Number of participants with potentially clinically significant body weight changes. Through Week 28 (end of study)
Primary Number of participants with 12-lead electrocardiogram (ECG) abnormalities and/or AEs Number of participants with potentially clinically significant 12-lead ECG values. Through Week 28 (end of study)
Primary Number of participants with laboratory value abnormalities and/ or AEs Number of participants with potentially clinically significant laboratory values. Through Week 28 (end of study)
Primary Number of participants with vital sign abnormalities and/ or AEs Number of participants with potentially clinically significant vital sign values. Through Week 28 (end of study)
Primary Number of participants with suicidal ideation and/ or behavior as assessed Columbia-Suicide Severity Rating Scale (C-SSRS) The Columbia-Suicide Severity Rating Scale (C-SSRS) is a clinician administered assessment tool that evaluates suicidal ideation and behavior. Number of participants that have an affirmative response provided to the 5 items for suicidal ideation (1. Wish to be dead, 2. Nonspecific active suicidal thoughts, 3. Active suicidal ideation with any methods (not plan) without intent to act, 4. Active suicidal ideation with some intent to act, without specific plan, 5. Active suicidal ideation with specific plan and intent) and/or to the 6 items for suicidal behavior (1. Actual attempt, 2. Interrupted attempt, 3. Aborted attempt, 4. Preparatory acts or behavior, 5. Suicidal Behavior 6. Completed suicide). Through Week 28 (end of study)
Primary Change from baseline in distance walked in 6 minutes assessed in meters The 6-minute walk test (6MWT) is a measurement of endurance that assesses walking distance over 6 minutes. Baseline and Week 24
Secondary Change from baseline in quality of life in neurological disorders (Neuro-QoL) Short Form Fatigue and Lower Extremity Function (Mobility) scores The Neuro-QoL Short Form Fatigue score is an 8-item self- assessment questionnaire evaluating the perception of fatigue and its impact in daily life activities. Participants have five response options for each item: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always. The questionnaire is scored by adding the response to each of the items. Higher scores indicate a greater level of fatigue. Baseline and Week 24
Secondary Change from baseline in time spent on the 5 Times Sit to Stand (5XSTS) test Change from baseline in time spent on the 5XSTS test. The test requires participants to sit with arms folded across chest and back against the chair and stand up and sit down 5 times in a row, as quickly as he/she can. Baseline and Week 24
Secondary Change from baseline in Modified Fatigue Impact Scale (MFIS) MFIS is a modified form of the Fatigue Impact Scale questionnaire specific to measuring how fatigue impacts the lives of those affected by fatigue-like symptoms. The 21 items in the scale measure three domains of fatigue including physical, cognitive and psychosocial functioning. Participants have five response options for each item: 0=Never, 1=Rarely, 2=Sometimes, 3=Often, and 4=Almost always. The scale is scored by adding the response to each of the items. Higher scores indicate a greater level of fatigue. Baseline and Week 24
Secondary Score on Patient Global Impression of Change (PGIC) The Patient Global Impression of Change evaluates participant's most bothersome symptom and assesses if there has been an improvement or decline in clinical status. Ratings range from (1) very much improved to (7) very much worse. Week 24
Secondary Change from baseline in Patient Global Impression of Severity (PGIS) The Patient Global Impression of Severity questionnaire assesses patient's impression of disease severity. The questionnaire asks the participant to best describe the severity of the participant's most bothersome pre-defined symptom over the past week scored from (1) None to (4) Severe. Baseline and Week 24
See also
  Status Clinical Trial Phase
Terminated NCT03323749 - A Trial to Evaluate Safety and Efficacy of Elamipretide Primary Mitochondrial Myopathy Followed by Open-Label Extension Phase 3
Completed NCT04535609 - An Efficacy and Safety Study of 24 Week Treatment With Mavodelpar (REN001) in Primary Mitochondrial Myopathy Patients Phase 2
Terminated NCT03862846 - A Study of the Safety of REN001 in Patients With Primary Mitochondrial Myopathy Phase 1
Terminated NCT05267574 - An Open Label, Long Term Safety Study of REN001 in Primary Mitochondrial Myopathy Patients (Stride Ahead) Phase 2/Phase 3