Safety, PK and Biodistribution of 18F-OP-801 in Patients With ALS, AD, MS, PD and Healthy Volunteers

Launched by ASHVATTHA THERAPEUTICS, INC. · May 25, 2022

Keywords

ClinConnect Summary

This clinical trial is exploring a new imaging agent called 18F-OP-801, which is designed to help detect inflammation in the brain related to conditions like Amyotrophic Lateral Sclerosis (ALS), Alzheimer's Disease (AD), Multiple Sclerosis (MS), and Parkinson's Disease (PD), as well as in healthy volunteers. The goal is to assess how safe and well-tolerated this agent is in people with these conditions, compared to those without them.

To participate, individuals should be between the ages of 18 and 80, depending on their specific condition. They need to be able to understand and sign consent forms and meet certain health criteria, such as having specific diagnoses and stable health conditions. Participants can expect to undergo imaging tests and will need to adhere to guidelines about medications and other health-related practices. Importantly, the study is currently recruiting participants, so there is an opportunity for eligible individuals to contribute to this important research.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Has the ability to understand and sign the written ICF and local medical privacy authorization forms, which must be obtained prior to the conduct of any study related procedures.
• • 2. Female subjects of non-childbearing potential must be either surgically sterile (hysterectomy, bilateral tubal ligation, salpingectomy, and/or bilateral oophorectomy at least 26 weeks before the Screening Visit) or postmenopausal, defined as spontaneous amenorrhea for at least 2 years, with follicle-stimulating hormone (FSH) in the postmenopausal range at screening, based on the local laboratory's defined ranges.
• 3. Female subjects of childbearing potential (i.e., ovulating, premenopausal, and not surgically sterile) and all male subjects must agree to practice abstinence from sexual intercourse or use a medically accepted contraceptive regimen (including hormonal contraceptives) during their participation in the study and for 90 days (males) or 6 months (females) after Day 1. Medically accepted contraceptive methods are defined as those with 90% or greater efficacy and are as follows:
• • 1. Male subjects: condoms or surgical sterilization of subject at least 26 weeks before the Screening Visit (i.e., vasectomy).
• 2. Female subjects:
• • 1. Surgical sterilization at least 26 weeks before the Screening Visit (includes hysterectomy or bilateral tubal ligation, bilateral oophorectomy, or salpingectomy);
• • 2. Intrauterine device or diaphragm with spermicide for at least 12 weeks before the Screening Visit; or
• • 3. Hormonal contraception (oral, implant, injection, ring, or patch) for at least 12 weeks before the Screening Visit.
• • 4. If male, subjects must agree to abstain from sperm donation through 90 days after the Day 1 Visit.
• • 5. Female subjects may not be pregnant, lactating, or breastfeeding.
• • 6. Female subjects of childbearing potential must have negative result for pregnancy test at Screening and Check-in.
• • 7. Subjects must have an estimated glomerular filtration rate (eGFR) of \>45 mL/min/1.73m2 at Screening.
• • 8. C-reactive protein level ≤10 mg/dL.
• • 9. Subjects must be willing and able to abide by all study requirements and restrictions.
• Inclusion Criteria Specific to ALS Subjects:
• • 10. Adult (Age 18 to 80, inclusive) at the Screening Visit
• • 11. Sporadic or familial ALS diagnosed as possible, laboratory-supported probable, probable, or definite as defined by the modified El Escorial criteria.
• • 12. Forced vital capacity (FVC) of ≥50%; or if in the opinion of the investigator can lay flat for up to 90 minutes. If FVC has been performed within the past 6 months, this data may be used at the discretion of the investigator.
• • 13. For ALS subjects, medication changes within 30 days prior to the Screening Visit should be discussed with the Medical Monitor.
• • Inclusion Criteria Specific to AD Subjects
• • 14. Adult (Age 40 to 80, inclusive) at the Screening Visit
• • 15. Clinical diagnosis of early stage dementia, Alzheimer type, plus positive Aβ and tau PET imaging, cerebrospinal fluid (CSF) and/or plasma biomarkers consistent with 2018 NIA-AA criteria
• • 16. MMSE score \>20 at Screening
• • 17. AD medication changes within 30 days prior to the Screening Visit should be discussed with the Medical Monitor.
• Inclusion Criteria Specific to MS Subjects:
• • 18. Adult (Age 18 to 70, inclusive) at the Screening Visit
• • 19. MS medication changes within 30 days prior to the Screening Visit should be discussed with the Medical Monitor.
• Inclusion criteria specific to subjects with RRMS:
• • 20. Diagnosis of RRMS based on 2017 McDonald criteria
• • 21. If not newly diagnosed, subjects should have at least 1 documented relapse in the last 24 months.
• • 22. "Active disease" subjects should have at least 1 Gadolinium-enhancing (Gd+) T1-weighted brain or spinal cord lesion at Screening MRI.
• • 23. "Disease in remission" subjects should have no Gd+ T1-weighted brain or spinal cord lesions at Screening MRI and stable clinical symptoms for at least 3 months prior to Day 1.
• • 24. EDSS score between 2.0 and 5.5 inclusive at Screening
• Inclusion criteria specific to subjects with progressive MS:
• • 25. Diagnosis of PPMS or SPMS based on 2017 McDonald criteria
• • 26. EDSS score between 3.0 and 6.5 inclusive at Screening
• • 27. No evidence of relapse in the prior 6 months
• • 28. Neurological exam and symptom stability for ≥30 days prior to Day 1
• • 29. Documented evidence of disability progression in the past 24 months not temporally related to a relapse
• Inclusion Criteria Specific to PD Subjects:
• • 30. Adult (Age 55 to 80, inclusive) at the Screening Visit
• • 31. Diagnosis of definite, idiopathic Parkinson's disease according to UK Parkinson's Society Brain Bank diagnostic criteria
• • 32. PD medication changes within 30 days prior to the Screening Visit should be discussed with the Medical Monitor.
• Overall Exclusion Criteria - For All Subjects:
• Subjects meeting any of the following criteria will be excluded from this study:
• • 1. Body weight \>120 kg
• • 2. Evidence of clinically significant or past medical history of hematologic, renal, endocrine, pulmonary, cardiac, gastrointestinal, hepatic, psychiatric, neurologic, immunologic, allergic disease (including multiple or clinically significant drug allergies) or any other condition that, in the opinion of the Investigator, might significantly interfere with the absorption, distribution, metabolism or excretion of study drug or place the subject at an unacceptable risk as a participant in this study
• • 3. History of recurrent kidney or liver malignancy
• • 4. Pacemaker or defibrillator or any non-removable metallic foreign objects in the body not compatible with MRI
• • 5. Inability to lie in a PET/CT or PET/MRI scanner for up to 90 minutes at a time
• • 6. Laboratory results (serum chemistry, hematology, coagulation and urinalysis) outside the normal range at Screening and Check-In and considered clinically significant in the opinion of the Investigator. Any elevation of aspartate transaminase (AST) and alanine transaminase (ALT) more than 3 times above the upper limit of normal at screening and/or check-in is exclusionary. One retest of an exclusionary laboratory result is allowed at the discretion of the Investigator and with approval from the Medical Monitor.
• • 7. Resolved acute illness considered clinically significant by the Investigator within 10 days prior to Screening
• • 8. History of alcoholism or drug abuse within 2 years prior to Screening. No cannabinoid drug use for at least 10 days prior to Day 1.
• • 9. Positive urine drug test, marijuana test or cotinine test at Screening or Check-In
• • 10. Any immunizations within the 28 days prior to screening
• • 11. Received any other investigational medicinal product within 30 days or 5 half-lives (whichever is longer) prior to Day 1
• • 12. Corticosteroid treatment (e.g., prednisone, solumedrol) within 30 days of Baseline
• • 13. Treatment with any of the following classes of nonsteroidal anti-inflammatory drugs (NSAIDS): carboxylic acids, enolic acids, cyclooxygenase (COX) II inhibitors within 14 days of Day 1
• • 14. Lost or donated \>450 mL of whole blood or blood products within 30 days prior to Screening
• • 15. MRI exclusion criteria: findings that may interfere with interpretation of the PET imaging, including but not limited to significant cortical/subcortical cerebrovascular disease, infectious disease, space-occupying lesions, hydrocephalus or other abnormalities associated with CNS disease not related to ALS, AD, MS or PD
• • 16. CT exclusion criteria include any medical device or metallic implant that may interfere with image acquisition or affect image reconstruction (e.g., CT attenuation correction).
• • 17. Investigator has reason to believe that the subject may be unable to fulfill the protocol visit schedule or requirements
• • 18. Has any finding that, in the view of the Investigator and Medical Monitor, would compromise the subject's safety in the trial
• Exclusion Criteria Specific to MS Subjects:
• • 19. Clinical signs or laboratory findings suggestive of neuromyelitis optica (NMO) spectrum disorders or myelin oligodendrocyte glycoprotein (MOG)-associated encephalomyelitis (i.e., presence of anti-NMO \[aquaporin-4\] antibodies or anti-MOG antibodies)
• • 20. Diagnosis of progressive multifocal leukoencephalopathy (PML)
• Exclusion Criteria Specific to PD Subjects:
• • 21. Secondary, atypical, or genetic parkinsonism
• Exclusion Criteria Specific to HV Subjects:
• • 22. Clinically relevant finding on physical examination at Screening
• • 23. Family history of neurological disease that may confound interpretation of imaging results
• • 24. History of any central nervous system disorder or brain trauma that could cause imaging abnormalities in the opinion of the Principal Investigator and Medical Monitor