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Safety and Dosimetry of a New Radiotracer to Detect Misfolded SOD1 Associated With Amyotrophic Lateral Sclerosis

Primary Purpose

Amyotrophic Lateral Sclerosis

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
89Zr-DFO-AP-101
Sponsored by
Université de Sherbrooke
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Amyotrophic Lateral Sclerosis focused on measuring PET imaging, CT imaging, AP-101, 89-Zirconium

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Aged of: For healthy participants: Male or female subjects aged 50 years or older For ALS patients: Male or female subjects aged 18 years and older Able to remain in a lying position for up to 45 minutes without respiratory support. A) For ALS patients, confirmed diagnostic of definitive ALS according to El-Escorial criteria14 B) for healthy participants: no neurologic condition (confirmed by physical exam) Have venous access sufficient to allow for blood sampling Are reliable and willing to make themselves available for the duration of the study and are willing to follow CRCHUS-specific study procedures. Exclusion Criteria: Are currently enrolled or were enrolled in the last 12 weeks in any other clinical trial involving a study drug or off label use of a drug or device, or any other type of medical research judged not to be scientifically or medically compatible with this study. Female participants who are pregnant or breast feeding; or women of childbearing potential (<50 years old) and men who are sexually active who are not willing to use an accepted effective contraceptive method. Plan to have surgery or other invasive procedure during the course of the study (up to 14 days post-injection) Have a progressive medical illness including, but not limited to, any cardiovascular, hepatic, respiratory, hematological, endocrine, psychiatric or neurological disease, convulsions, or any clinically significant laboratory abnormality at screening and at first visit (D0) that, in the judgment of the medical doctor, indicate a medical problem that would preclude study participation. Have one of these conditions (for both patient groups): hepatic disorder such as hepatic encephalopathy, hepatic laboratory abnormalities (ALT or AST ≥3 × ULN or total bilirubin ≥2 × ULN) and hematology abnormalities at screening. severe chronic kidney disease (eg, an estimated glomerular filtration rate [eGFR] <30 mL/min/1.73m or requires chronic dialysis) at screening. Have severe active psychiatric illness. Have a diagnosis of another neurodegenerative disease (e.g. Parkinson disease, Alzheimer's disease, etc). Have a significant infection or known inflammatory process on screening or at Day 0. Alcohol or drug abuse based on patient auto-report Have a history of relevant atopy or drug hypersensitivity or allergy to antibodies; Have an abnormal blood pressure (supine) defined as a diastolic blood pressure >90 or <45 mmHg and/or a systolic blood pressure >160 or <90 mmHg. Re-testing may occur once during the screening visit within 2 hours of the initial abnormal blood pressure measurement at the discretion of the investigator. For ALS patients: Have undergone a tracheostomy for ALS symptoms. Are on nasal intermittent positive pressure ventilation (NIPPV) >4h during the day, while awake for the treatment of ALS related symptoms. Have other causes of neuromuscular weakness. Have received treatment with biologic agents (such as monoclonal antibodies, including marketed drugs and AP-101) within 3 months or 5 half-lives (whichever is longer) prior to study drug injection. Have received any blood or blood products within the 3 months prior to screening. Cannot communicate reliably with the investigator. Are unwilling or unable to give written informed consent. In the opinion of the medical doctor or his/her delegate, are unsuitable for inclusion in the study.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Experimental

    Arm Label

    Healthy participants

    Patients with ALS

    Arm Description

    Will receive 40MBq of 89Zr-DFO-AP-101, once, at Day 0.

    Will receive 40MBq of 89Zr-DFO-AP-101, once, at Day 0.

    Outcomes

    Primary Outcome Measures

    Incidence of adverse events (AEs) and serious adverse events (SAEs)
    Number of adverse events (AEs) and serious adverse events following administration of [89Zr]Zr-DFO-AP-101 that are new or worsened (compared to baseline/pre-dose)
    Biodistribution of [89Zr]Zr-DFO-AP-101
    Assessed by whole-body PET imaging
    Dosimetry of [89Zr]Zr-DFO-AP-101 in human
    Organ activity concentration (in liver, kidneys, blood, spleen, ...) measured by drawing region of interests on the PET images.

    Secondary Outcome Measures

    Cmax
    Maximal concentration of [89Zr]Zr-DFO-AP-101 in plasma over time after injection
    Area under the curve (AUC)
    AUC of [89Zr]Zr-DFO-AP-101 in plasma over time after injection
    residence time
    Time (1/2) of residence of [89Zr]Zr-DFO-AP-101 in plasma
    Excretion
    Concentration of [89Zr]Zr-DFO-AP-101 urine over time

    Full Information

    First Posted
    July 11, 2023
    Last Updated
    July 26, 2023
    Sponsor
    Université de Sherbrooke
    Collaborators
    Eli Lilly and Company, Chorus Wellness Inc., AL-S Pharma AG
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05974579
    Brief Title
    Safety and Dosimetry of a New Radiotracer to Detect Misfolded SOD1 Associated With Amyotrophic Lateral Sclerosis
    Official Title
    A Single Center, Open Label Study to Evaluate Biodistribution, Pharmacokinetics and Safety of [89Zr]Zr-DFO-AP-101 PET (Positron Emission Tomography) in Healthy Volunteers and Amyotrophic Lateral Sclerosis (ALS) Patients
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    September 1, 2023 (Anticipated)
    Primary Completion Date
    May 31, 2024 (Anticipated)
    Study Completion Date
    July 31, 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Université de Sherbrooke
    Collaborators
    Eli Lilly and Company, Chorus Wellness Inc., AL-S Pharma AG

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's Disease, is a rare neurodegenerative disease resulting in loss, primarily, of the motor neurons in the motor cortex, brainstem and spinal cord. It currently affects 3 of every 100,000 people in the US. Currently, there is no diagnostic tool for ALS, resulting in misdiagnosis and significant disease progression before formal diagnosis. An imaging test for early detection of ALS and for monitoring disease progression would have significant diagnostic and prognostic value. PET imaging with an appropriate radiotracer has great potential as a biomarker for ALS given that it would permit visualization of central nervous system (CNS) pathology in individuals living with the disease. To that extent, the primary goal of this phase I study is evaluating the safety and biodistribution of the new tracer [89Zr]Zr-DFO-AP-101 in healthy volunteers and ALS patients.
    Detailed Description
    Background: Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's Disease, is a rare neurodegenerative disease resulting in loss, primarily, of the motor neurons in the motor cortex, brainstem and spinal cord. It currently affects 3 of every 100,000 people in the US. Currently, there is no diagnostic tool for ALS, resulting in misdiagnosis and significant disease progression before formal diagnosis. Design: This is a phase I clinical trial and a 2-part, single center, open label study in healthy volunteers (Part A) and confirmed ALS patients (Part B). The primary goal is evaluating the safety and biodistribution of the radiotracer [89Zr]Zr-DFO-AP-101 in healthy volunteers and ALS patients via PET/CT imaging. Objectives: The primary objectives of this study are: (Part A) To evaluate, by PET imaging, the safety, biodistribution and dosimetry of [89Zr]Zr-DFO-AP-101 in healthy men and women and in ALS patients Intervention and Follow-up: Following a screening visit, eligible participants will come to the research center for all study assessments. On Day 0, a single intravenous dose of [89Zr]Zr-DFO-AP-101 40 MBq will be administrated and a 45 min whole body PET/CT acquisition will be performed at two hours post injection. Physical exam, ECG, vital signs and blood/urine samples will be collected. Further PET acquisitions and same data/samples collection will be repeated at days 1, 3, 7 and 10 post-injection. Participants will be contacted for a final follow-up visit approximately 14 days after injection.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Amyotrophic Lateral Sclerosis
    Keywords
    PET imaging, CT imaging, AP-101, 89-Zirconium

    7. Study Design

    Primary Purpose
    Diagnostic
    Study Phase
    Phase 1
    Interventional Study Model
    Parallel Assignment
    Model Description
    Two groups will be enrolled: 8 healthy subjects and 4 patients with ALS This is non-randomized, all participants will receive the same dose of radiotracer
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    12 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Healthy participants
    Arm Type
    Experimental
    Arm Description
    Will receive 40MBq of 89Zr-DFO-AP-101, once, at Day 0.
    Arm Title
    Patients with ALS
    Arm Type
    Experimental
    Arm Description
    Will receive 40MBq of 89Zr-DFO-AP-101, once, at Day 0.
    Intervention Type
    Drug
    Intervention Name(s)
    89Zr-DFO-AP-101
    Intervention Description
    At Day 0, patients will receive one dose of the radiotracer. A PET/CT scan will be done pre- and 2h post-dose. At 1, 3, 7 and 10 days post-dose, a PET/CT scan will be repeated.
    Primary Outcome Measure Information:
    Title
    Incidence of adverse events (AEs) and serious adverse events (SAEs)
    Description
    Number of adverse events (AEs) and serious adverse events following administration of [89Zr]Zr-DFO-AP-101 that are new or worsened (compared to baseline/pre-dose)
    Time Frame
    day 0 (post-injection) to day 14 (end of study)
    Title
    Biodistribution of [89Zr]Zr-DFO-AP-101
    Description
    Assessed by whole-body PET imaging
    Time Frame
    Pre-dose and at 2 hours, 1, 3, 7, 10 days post-dose
    Title
    Dosimetry of [89Zr]Zr-DFO-AP-101 in human
    Description
    Organ activity concentration (in liver, kidneys, blood, spleen, ...) measured by drawing region of interests on the PET images.
    Time Frame
    Pre-Dose and at 2 hours, 1, 3, 7, 10 days post-dose
    Secondary Outcome Measure Information:
    Title
    Cmax
    Description
    Maximal concentration of [89Zr]Zr-DFO-AP-101 in plasma over time after injection
    Time Frame
    Pre-dose and at 2 hours, 1, 3, 7, 10 days post-dose
    Title
    Area under the curve (AUC)
    Description
    AUC of [89Zr]Zr-DFO-AP-101 in plasma over time after injection
    Time Frame
    Pre-dose and at 2 hours, 1, 3, 7, 10 days post-dose
    Title
    residence time
    Description
    Time (1/2) of residence of [89Zr]Zr-DFO-AP-101 in plasma
    Time Frame
    Pre-dose and at 2 hours, 1, 3, 7, 10 days post-dose
    Title
    Excretion
    Description
    Concentration of [89Zr]Zr-DFO-AP-101 urine over time
    Time Frame
    Pre-dose and at 2 hours, 1, 3, 7, 10 days post-dose
    Other Pre-specified Outcome Measures:
    Title
    Differential labeling and uptake
    Description
    Assessment of target organ/tissue ratio in ALS patients versus healthy volunteers
    Time Frame
    Pre-dose and at 2 hours, 1, 3, 7, 10 days post-dose

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    Inclusion Criteria: Aged of: For healthy participants: Male or female subjects aged 50 years or older For ALS patients: Male or female subjects aged 18 years and older Able to remain in a lying position for up to 45 minutes without respiratory support. A) For ALS patients, confirmed diagnostic of definitive ALS according to El-Escorial criteria14 B) for healthy participants: no neurologic condition (confirmed by physical exam) Have venous access sufficient to allow for blood sampling Are reliable and willing to make themselves available for the duration of the study and are willing to follow CRCHUS-specific study procedures. Exclusion Criteria: Are currently enrolled or were enrolled in the last 12 weeks in any other clinical trial involving a study drug or off label use of a drug or device, or any other type of medical research judged not to be scientifically or medically compatible with this study. Female participants who are pregnant or breast feeding; or women of childbearing potential (<50 years old) and men who are sexually active who are not willing to use an accepted effective contraceptive method. Plan to have surgery or other invasive procedure during the course of the study (up to 14 days post-injection) Have a progressive medical illness including, but not limited to, any cardiovascular, hepatic, respiratory, hematological, endocrine, psychiatric or neurological disease, convulsions, or any clinically significant laboratory abnormality at screening and at first visit (D0) that, in the judgment of the medical doctor, indicate a medical problem that would preclude study participation. Have one of these conditions (for both patient groups): hepatic disorder such as hepatic encephalopathy, hepatic laboratory abnormalities (ALT or AST ≥3 × ULN or total bilirubin ≥2 × ULN) and hematology abnormalities at screening. severe chronic kidney disease (eg, an estimated glomerular filtration rate [eGFR] <30 mL/min/1.73m or requires chronic dialysis) at screening. Have severe active psychiatric illness. Have a diagnosis of another neurodegenerative disease (e.g. Parkinson disease, Alzheimer's disease, etc). Have a significant infection or known inflammatory process on screening or at Day 0. Alcohol or drug abuse based on patient auto-report Have a history of relevant atopy or drug hypersensitivity or allergy to antibodies; Have an abnormal blood pressure (supine) defined as a diastolic blood pressure >90 or <45 mmHg and/or a systolic blood pressure >160 or <90 mmHg. Re-testing may occur once during the screening visit within 2 hours of the initial abnormal blood pressure measurement at the discretion of the investigator. For ALS patients: Have undergone a tracheostomy for ALS symptoms. Are on nasal intermittent positive pressure ventilation (NIPPV) >4h during the day, while awake for the treatment of ALS related symptoms. Have other causes of neuromuscular weakness. Have received treatment with biologic agents (such as monoclonal antibodies, including marketed drugs and AP-101) within 3 months or 5 half-lives (whichever is longer) prior to study drug injection. Have received any blood or blood products within the 3 months prior to screening. Cannot communicate reliably with the investigator. Are unwilling or unable to give written informed consent. In the opinion of the medical doctor or his/her delegate, are unsuitable for inclusion in the study.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Amelie Tetu, MSc
    Phone
    819-346-1110
    Email
    amelie.tetu.ciussse-chus@ssss.gouv.qc.ca
    First Name & Middle Initial & Last Name or Official Title & Degree
    Sarah Côté-Bigras, MSc
    Phone
    819-346-1110
    Email
    sarah.cote-bigras.ciussse-chus@ssss.gouv.qc.ca
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Eric E Turcotte, MD
    Organizational Affiliation
    Estrie University Integrated Health and Social Services Center - University Hospital of Sherbrooke
    Official's Role
    Study Director
    First Name & Middle Initial & Last Name & Degree
    Brigitte Guérin, PhD
    Organizational Affiliation
    Estrie University Integrated Health and Social Services Center - University Hospital of Sherbrooke
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No

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    Safety and Dosimetry of a New Radiotracer to Detect Misfolded SOD1 Associated With Amyotrophic Lateral Sclerosis

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