A Study to Evaluate the Safety, Pharmacokinetics and Biodistribution of an Imaging Agent, 18F-OP-801 (18F Hydroxyl Dendrimer) in Patients With Amyotrophic Lateral Sclerosis (ALS) and Healthy Volunteers (HV)

• ClinicalTrials.gov Identifier: NCT05395624
• Recruitment Status: Recruiting
• First Posted: May 27, 2022
• Last Update Posted: February 13, 2023
• Sponsor: Ashvattha Therapeutics, Inc.
• Information provided by (Responsible Party): Ashvattha Therapeutics, Inc.

Tracking Information

• First Submitted Date: May 13, 2022
• First Posted Date: May 27, 2022
• Last Update Posted Date: February 13, 2023
• Actual Study Start Date: February 2, 2023
• Estimated Primary Completion Date: June 30, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 25, 2022)

The number of participants with treatment emergent adverse events (Safety and Tolerability) [ Time Frame: Safety and tolerability of 18F-OP-801 as assessed by the frequency, and severity of treatment-emergent adverse events (TEAEs) from Day 1 to Day 15 or Day 18 ]

Safety of single dose of 18F-OP-801 as measured by treatment-related adverse events as assessed by CTCAE v5.0

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 25, 2022)

• Measurement of biodistribution of 18F-OP-801 for each participant [ Time Frame: Through study completion at Day 15 or Day 18 ]
  Measure biodistribution of 18F-OP-801 using whole body PET/MRI or PET/computed tomography (CT) scans
• Uptake of 18F-OP-801 in ALS participants [ Time Frame: Through study completion at Day 15 or Day 18 ]
  Determination of the correlation between MRI and PET images in the same ALS subjects, quantifying the extent of 18F-OP-801 uptake in the region of neuroinflammation relative to normal brain section in the same ALS subject as measured by whole body PET/MRI or PET/CT scans
• Measurement of clearance of 18F-OP-801 for each participant [ Time Frame: Through study completion at Day 15 or Day 18 ]
  Measure clearance of 18F-OP-801 using whole body PET/MRI or PET/computed tomography (CT) scans

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate the Safety, Pharmacokinetics and Biodistribution of an Imaging Agent, 18F-OP-801 (18F Hydroxyl Dendrimer) in Patients With Amyotrophic Lateral Sclerosis (ALS) and Healthy Volunteers (HV)
• Official Title: A Phase 1 Study to Evaluate the Safety, Pharmacokinetics and Biodistribution of an Imaging Agent, 18F-OP-801 (18F Hydroxyl Dendrimer), After Intravenous Administration to Patients With Amyotrophic Lateral Sclerosis (ALS) and Healthy Volunteers (HV)
• Brief Summary: A Phase 1 Study to Evaluate the Safety, Pharmacokinetics and Biodistribution of an Imaging agent, 18F-OP-801 (18F Hydroxyl Dendrimer), After Intravenous Administration to Patients with Amyotrophic Lateral Sclerosis (ALS) and Healthy Volunteers (HV)
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Diagnostic
• Condition: Amyotrophic Lateral Sclerosis (ALS)

Intervention

Drug: 18F-OP-801

18F Hydroxyl Dendrimer

Other Name: 18F Hydroxyl Dendrimer

Study Arms

• Experimental: Healthy Volunteers participants
  Intravenous Administration of 18F-OP-801 (18F Hydroxyl Dendrimer)
  Intervention: Drug: 18F-OP-801
• Experimental: Amyotrophic Lateral Sclerosis participants
  Intravenous Administration of 18F-OP-801 (18F Hydroxyl Dendrimer)
  Intervention: Drug: 18F-OP-801

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 9, 2023): 26
• Original Estimated Enrollment (submitted: May 25, 2022): 25
• Estimated Study Completion Date: June 30, 2023
• Estimated Primary Completion Date: June 30, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Adult (Age 18-80, inclusive) at the Screening Visit.
2. 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.
3. 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.
4. Female subjects of childbearing potential (i.e., ovulating, premenopausal, and not surgically sterile) and all male subjects must 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.

5. Acceptable methods of contraception for male subjects enrolled in the study include the following:

   1. Condoms or surgical sterilization of subject at least 26 weeks before the Screening Visit (i.e., vasectomy).

      Acceptable methods of contraception for female subjects enrolled in the study include the following:

   2. Surgical sterilization at least 26 weeks before the Screening Visit (includes hysterectomy or bilateral tubal ligation, bilateral oophorectomy, or salpingectomy);
   3. Intrauterine device or diaphragm with spermicide for at least 12 weeks before the Screening Visit; or
   4. Hormonal contraception (oral, implant, injection, ring, or patch) for at least 12 weeks before the Screening Visit.
6. If male, subjects must agree to abstain from sperm donation through 90 days after the Day 1 Visit.
7. Female subjects may not be pregnant, lactating, or breastfeeding.
8. Female subjects of childbearing potential must have negative result for pregnancy test at Screening and Check-in.
9. Subjects must have an estimated glomerular filtration rate (eGFR) of >45 mL/min/1.73m2 at Screening.
10. C-reactive protein level ≤10 mg/dL.

11. Subjects must be willing and able to abide by all study requirements and restrictions.

    Inclusion Specific to ALS Subjects:

12. Serum NfL concentration at Screening Visit above the 95th percentile of the reference range for healthy subjects of the same age (using reference data).
13. Sporadic or familial ALS diagnosed as possible, laboratory-supported probable, probable, or definite as defined by the modified El Escorial criteria.
14. ALS cognitive behavioral screen score >10 on the cognitive scale and/or >32 on the behavioral scale.
15. 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.
16. Medications for ALS subjects should be stable for 30 days prior to the Screening Visit and remain unchanged during the subject's participation in the study.

Exclusion Criteria:

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.
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 the above 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, 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 of the investigational medicinal product (whichever is longer) prior to Day 1.
12. Treatment with immunosuppressive agents (e.g., prednisone, solumedrol) within 30 days of Day 1. Treatment with anti-inflammatory agents including any medications in the following classes of nonsteroidal anti-inflammatory drugs (NSAIDS): carboxylic acids, enolic acids, cyclooxygenase (COX) II inhibitors within 14 days of Day 1.
13. Lost or donated >450 mL of whole blood or blood products within 30 days prior to screening.
14. MRI exclusion criteria include: 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.
15. 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).
16. Investigator has reason to believe that the subject may be unable to fulfill the protocol visit schedule or requirements.
17. Has any finding that, in the view of the Investigator and Medical Monitor, would compromise the subject's safety requirements.

18. Is employed by the Sponsor, the CRO, or the study site (permanent, temporary contract worker, or designee responsible for the direct conduct of the study), or is a family member (spouse, parent, sibling, or child) of the Sponsor, CRO, or study site employee.

    Exclusion Criteria Specific to HV Subjects:

19. Clinically relevant finding on physical examination at screening.
20. Family history of ALS or frontotemporal dementia.

21. History of any central nervous system disorder or brain trauma (concussions, etc.).

    1. Medical monitor must be consulted for potential inclusion of subject with history of CNS involvement.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Jenni Herber; 650-505-5058; jherber@avttx.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05395624
• Other Study ID Numbers: OP-801-001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Ashvattha Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Ashvattha Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Ashvattha Therapeutics, Inc.
• Verification Date: February 2023