A Study of BHV-3241 in Subjects with Multiple System Atrophy

Overview

About this study

The purpose of this study is to compare the effectiveness of BHV-3241 versus placebo in subjects with Multiple System Atrophy.

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: 

  • Subjects must provide a written signed and dated informed consent form/forms (IRB/EC specific) in accordance with regulatory and institutional guidelines, prior to the initiation of any protocol required procedures. Only patients with the capacity to understand the nature, significance and scope of the clinical trial interventions and to express their wishes accordingly may provide consent to participate in the study.
  • Caregivers must be willing to sign and date an IRB/EC-approved written informed consent form that outlines the caregiver expectations and responsibilities in this study in accordance with regulatory and institutional guidelines, as appropriate.
  • Male and female subjects between the ages of > 40 to < 80 years at time of Screening.
  • Diagnosis of probable or possible MSA according to consensus clinical criteria (Gilman et al 2008), including subjects with MSA of either subtype (MSA-P or MSA-C).
  • Able to ambulate without the assistance of another person, defined as the ability to take at least 10 steps. Use of assistive devices (e.g., walker or cane) is allowed.
  • Anticipated survival of at least 3 years at the time of Screening, as judged by the Investigator.
  • A brain MRI scan (conducted within the 14 days prior to Baseline/Day 1, approximately) that does not rule out a diagnosis of MSA.
  • Able to tolerate MRI.
  • Body mass index (BMI) < 40 kg/m2 at Screening.
  • Able to swallow tablets whole and anticipated to be able to do so throughout the duration of the study.
  • Willing and able to adhere to the study drug regimen.
  • Willing and able to perform all protocol-specified assessments and comply with the study visit schedule.
  • Able to read, understand, and speak local language fluently to ensure comprehension of informed consent and protocol-specified assessments.
  • Must have reliable caregiver to accompany subject to study visits, with the same caregiver completing caregiver assessments at Baseline, Week 24 and Week 48/Early Discontinuation, when possible. Caregiver must be able to read, understand, and speak local language fluently to ensure comprehension of informed consent and protocolspecified assessments. Caregiver must also have frequent contact with subject (at least 3 hours per week at one time or different times) and be willing to monitor the subject's health and concomitant medications throughout the study.
  • If subject is receiving treatment for MSA, the doses must have been stable for at least 30 days prior to Baseline/Randomization and medications present at Baseline expected to remain relatively stable during the study period. This may include medications commonly used for Parkinson's disease (e.g., coenzyme Q10, levodopa/carbidopa, levodopa/benserazide, fava bean extract, a dopamine agonist, catechol-0- methyltransferase inhibitor, amantadine) or those for autonomic dysfunction (e.g., ephedrine, midodrine, fludrocortisone, octreotide, desmopressin, oxybutynine, droxidopa).
  • Stable on other chronic medications and supplements for at least 30 days prior to Baseline/Randomization and expected to remain relatively stable during the study period.
  • Women of child bearing potential (WOCBP) and fertile men (including those vasectomized for less than 6 months) with female partners who are WOCBP (not surgically sterile and not postmenopausal) must agree to use highly effective birth control, including two methods of contraception, for the duration of the study (i.e., beginning 30 days prior to Baseline/ Randomization and extending to 30 days for women and 90 days for men after the last dose of study drug). The two methods of contraception should include:
    • one barrier method (e.g., diaphragm with spermicide, condom with spermicidal gel, cervical cap); and
    • one other method that could include hormonal contraceptives (e.g., oral contraceptives, injectable contraceptives, contraceptive implant, patch) used for at least 4 weeks prior to sexual intercourse.
  • WOCBP must have a negative serum pregnancy test at Screening and a negative urine pregnancy test within approximately 24 hours prior to dosing at Baseline/ Randomization.

Exclusion Criteria:

  • Subjects having advanced disease, defined by the presence of one or more of the following on the UMSARS Part I:
    • Speech impairment, as assessed by a score greater than or equal to 3, Question 1;
    • Swallowing impairment, as assessed by a score of greater than or equal to 3 on Question 2;
    • Falling more frequently than once per week, as assessed by a score of greater than or equal to 3 on Question 8.
  • Subjects having significant cognitive impairment, defined by a score of less than or equal to 20 on the MoCA (score includes any limitation due to motor impairments).
  • Any condition that would interfere with the subject’s ability to comply with study instructions, place the subject at unacceptable risk, and/or confound the interpretation of safety or efficacy data from the study, as judged by the Investigator.
  • Diagnosis of neurological disorders, other than MSA, including (but not limited to) the following:
    • Idiopathic Parkinson's disease or another form of parkinsonism (e.g., dementia with Lewy bodies, drug-induced, post-encephalitic, vascular), which has not subsequently revised to a diagnosis of MSA;
    • Any other neurodegenerative disease (e.g., Alzheimer's disease, frontotemporal dementia, amyotrophic lateral sclerosis, prion disease);
    • Any other clinically significant neurological disorder (e.g., history of stroke, history of head injury with loss of consciousness for at least 15 minutes within the past 20 years, history of seizure disorder, brain tumor, or other space-occupying lesion).
  • History of or Screening brain MRI scan indicative of significant abnormality, including (but not limited to) the following:  prior hemorrhage or infarct greater than 1 cm3; 3 or more lacunar infarcts; cerebral contusion;  encephalomalacia; aneurysm;  vascular malformation; subdural hematoma; hydrocephalus; space-occupying lesion (e.g., abscess or brain tumor).
  • Contraindication to MRI examination for any reason.
  • For those participating in the optional CSF sub-study, contraindication to undergoing an LP including, but not limited to: inability to tolerate an appropriately flexed position for the time necessary to perform an LP; infection at the desired LP site; taking antiplatelet/ anticoagulant medications that cannot be discontinued for a short period of time prior to performing the LP; degenerative arthritis of the lumbar spine; suspected non-communicating hydrocephalus or intracranial mass; prior history of spinal mass or trauma.
  • Presence of clinically significant thyroid disease with abnormal free T4 levels and TSH >10 mIU/L (despite treatment) at Screening, confirmed by repeat.
  • Within 1 year prior to Screening or between Screening and Baseline (Day -1), any of the following: myocardial infarction; hospitalization for congestive heart failure; hospitalization for, or symptoms of, unstable angina; or syncope not related to MSA.
  • Diagnosis of clinically significant psychiatric disorder including (but not limited to) the following:  any psychotic disorder, severe bipolar or unipolar depression, prior history of suicidal thoughts or behavior that are believed to represent a current safety risk.
  • History of substance use disorder (drug or alcohol) in the last 12 months, with the exception of nicotine, as defined by DSM-V criteria.
  • History or presence of gastrointestinal or other disease known to interfere with absorption, distribution, metabolism, or excretion of drugs, or a history of surgery known to interfere with absorption or excretion of drugs (i.e., gastric bypass).
  • History of any other clinically significant disease (e.g., autoimmune, cardiovascular, endocrine, gastrointestinal, hematological, hepatic, immunological, infectious, neurological, pulmonary, psychiatric, or renal) that, based on the judgment of the Investigator, is clinically unstable, is likely to deteriorate during the course of the study, could put the patient at risk because of participation in the study, could affect the subject’s ability to complete the study, or could influence the study results.
  • History of human immunodeficiency virus infection.
  • Hematologic or solid malignancy diagnosis within 5 years prior to Screening.
    • Note: Subjects with a history of localized skin cancer, basal cell or squamous cell carcinoma, may be enrolled in the study as long as they are cancer free prior to randomization. Subjects with other localized cancers (without metastatic spread) who have previously completed their course of treatment more than 5 years prior to Screening, are not currently receiving treatment and have been in remission may be enrolled only if, in the opinion of the Investigator, there is no expectation for recurrence or further cancer treatment during the study period. Antihormonal therapy (e.g., tamoxifen) is allowed if the subject's cancer is in remission and the subject is on stable maintenance therapy to reduce their risk of recurrence.
  • Any major surgery within 4 weeks of Screening.
  • Blood transfusion within 4 weeks of Screening.
  • History of brain surgery for Parkinsonism (i.e., deep-brain stimulation).
  • History of stem-cell treatment.
  • Women who are pregnant or breastfeeding.
  • Subjects or prisoners who are involuntarily detained or incarcerated for treatment of either a psychiatric or physical illness must not be enrolled into the study.
  • Any medical condition, based on the judgement of the Investigator, that would confound the ability to adequately assess safety and efficacy outcome measures.
  • Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG, or clinical laboratory determinations beyond what is consistent with the target population.
  • Clinically significant abnormality on 12-lead ECG prior to study drug administration beyond what is consistent with the target population, confirmed by repeat.
  • QTcF (Fridericia) interval ≥ 470 msec during the Screening/Baseline period or uncontrolled arrhythmia or frequent premature ventricular contraction (PVCs) (> 5/minute) or Mobitz Type II second or third degree atrioventricular (AV) block or left bundle branch block, or right bundle branch block with a QRS duration ≥ 150 msec or intraventricular conduction defect with a QRS duration ≥ 150 msec or evidence of acute or sub-acute myocardial infarction or ischemia or other ECG findings that, in the Investigator’s opinion, would preclude participation in the study. d. Abnormal free T4 levels and TSH > 10 mIU/L (despite treatment) at Screening, confirmed by repeat.
  • Total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 2 times the upper limit of normal (ULN), confirmed by repeat. If the patient is diagnosed as having Gilbert’s syndrome, the patient can be discussed with the Medical Monitor.
  • Pathologic renal findings at Screening as defined by the presence of either of the following criteria:
    • Estimated glomerular filtration rate (eGFR) according to the re- expressed abbreviated (four-variable) Modification of Diet in Renal Disease (MDRD) Study equation < 30 ml/min/ 1.73m^2;
    • The MDRD estimation is calculated as follows: eGFR (mL/min/1.73m^2) = 175 x (standardized Scr)-1.154 x (Age)-0.203 x (0.742 if female) x (1.212 if Black). [Scr: Standardized serum creatinine];
    • Creatinine ≥ 2mg/dL g.
  • Hematologic abnormalities at Screening:
    • Hemoglobin < 10 g/dL; or
    • WBC < 3.0 x 103/mm^3; or
    • Platelet count < 100,000/mm^3; or
    • Neutrophils, Absolute ≤ 1000/mm^3;
    • Hemoglobin A1C > 7.5%, confirmed by repeat.
  • Urine drug screen positive for a drug of abuse, for which the patient does not have a valid prescription and is suspected of abusing, in the judgement of the Investigator.
    • Note: urine drug screen positive for cannabis is exclusionary unless the Investigator and Medical Monitor agree that the subject can abstain from use for the duration of the study, or if the subject has a valid medical prescription.
  • Human Immunodeficiency Virus (HIV) positive at Screening (indicated by positive confirmatory Western Blot).
  • HBsAg or HCV positive at Screening.
  • For WOCBP, positive serum β-hCG which is indicative of pregnancy and not false positive at Screening or a positive urine pregnancy test at Baseline.

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

Jacksonville, Fla.

Mayo Clinic principal investigator

Zbigniew Wszolek, M.D.

Closed for enrollment

Contact information:

Audrey Strongosky C.C.R.C.

(904)953-8308

Strongosky.Audrey2@mayo.edu

More information

Publications

Publications are currently not available
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CLS-20471965

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