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SLS-005 (Trehalose Injection) in the Treatment of Alzheimer's Disease ([STRIVE-AD])

Primary Purpose

Alzheimer's Disease

Status
Withdrawn
Phase
Phase 2
Locations
Australia
Study Type
Interventional
Intervention
SLS-005 - Once Weekly
SLS-005 - Twice Weekly
Sponsored by
Seelos Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alzheimer's Disease focused on measuring Trehalose, Phase II, Dementia, Australia, SLS-005, STRIVE-AD

Eligibility Criteria

50 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria

  1. Have a study partner/caregiver who, in the Investigator's judgment, has frequent and sufficient face-to-face contact with the participant (approximately 10 hours per week or more) and consents to attend all study visits, assist in ensuring compliance with all study requirements and procedures, and provide input into assessments of cognitive performance and functioning in daily activities throughout the full duration of the participant's involvement in the study.
  2. Signed informed consent from:

    1. The participant or person responsible/guardian
    2. The participant's study partner/caregiver
  3. Men and women, 50 to 85 years (inclusive) of age.
  4. Gradual and progressive change in cognitive performance has been observed for ≥ 6 months not associated with a specific event or medical condition e.g., head trauma, stroke, cardiac arrest, cerebrovascular disease, epilepsy, alcohol abuse, etc.
  5. Capable of completing study assessments either alone or with assistance from the study partner.
  6. Mini-mental status examination (MMSE) score ≥ 16 and ≤ 27 at screening.
  7. Modified Hachinski Score ≤ 4 at screening.
  8. Body Mass Index (BMI) between 20 kg/m2 and 32 kg/m2 (inclusive)
  9. Clinical Dementia Rating (CDR) global score of 0.5, 1.0, or 2.0 at screening.
  10. Clinical Dementia Rating - Sum of Boxes (CDR-SB) score ≥ 0.5 at screening.
  11. Lumbar Puncture during screening period with results for CSF Aβ42 or CSF that are consistent with a diagnosis of AD.
  12. Stable doses of all concomitant medications for at least 30 days prior to the baseline visit.
  13. For participants taking cholinesterase inhibitors and/or memantine, documentation of stable use for at least 12 weeks is required prior to screening.
  14. Negative serum beta-human chorionic gonadotropin (ß-hCG) pregnancy result at the screening visit for female participants of childbearing potential.
  15. Willingness to comply with sexual abstinence or contraception guidelines of this study.
  16. Willingness and ability to complete all study procedures, including brain magnetic resonance imaging (MRI), lumbar puncture, clinical genotyping, and brain positron emission tomography (PET).
  17. Participant and study partner/caregiver must be fluent in the English language for both reading and speaking.
  18. Participant and study partner/caregiver must be fully vaccinated as per local regulations for COVID-19 at least 2 weeks prior to screening.

Exclusion Criteria

  1. Presence of a neurologic or neuropsychiatric condition or imaging finding associated with a neurologic or neuropsychiatric condition other than AD that can be associated with dementia or confound the evaluation of dementia, including but not limited to Parkinson's disease, Huntington's disease, frontotemporal dementia, cerebrovascular disease, (diseases related to or events associated with disruption of blood flow to the brain), seizure disorders, inflammatory or infectious disorders of the central nervous system, normal pressure hydrocephalus, traumatic brain injury, uncontrolled major depression, psychosis, bipolar disorder, and long-term sequelae of alcohol or substance abuse.
  2. History of stroke or transient ischemic attack (TIA) within 12 months of screening.
  3. Epileptic or epileptiform seizure within 12 months of screening.
  4. Current participation in another clinical trial or completed participation in an interventional trial less than 30 days prior to the screening visit (90 days for a biological treatment).
  5. Involvement in an Aβ or tau vaccination trial for AD unless known to have received only placebo.
  6. Current diagnosis and/or healthcare professional-recommended treatment (medication and/or diet) of diabetes mellitus type 1 or type 2.
  7. Hemoglobin A1c (HbA1c) ≥ 6.5% at the screening visit
  8. Prior treatment with SLS-005, any other IV trehalose formulation, or known hypersensitivity to trehalose.
  9. Is receiving aducanumab or any other immunotherapy for treatment of dementia including AD.
  10. Regular use (≥ 3 days per week) of prescribed or pharmacy-purchased opiates, opioids, or benzodiazepines.
  11. Pregnant or breastfeeding.
  12. History of alcohol or drug abuse within the last 2 years.
  13. Chronic liver disease including Hepatitis B; Hepatitis C unless successful curative treatment is documented; human immunodeficiency virus (HIV) infection.
  14. Prior history of drug-induced liver injury (DILI) and/or laboratory results at screening that indicate inadequate liver function (e.g., alanine aminotransferase [ALT], aspartate aminotransferase [AST], gamma-glutamyl transferase [GGT] > 2 times the upper limit of normal [x ULN] and/or total bilirubin level > 2 x ULN).
  15. Laboratory results at screening that indicate inadequate renal function (e.g., estimated creatinine clearance of < 60 mL/min calculated by the Cockcroft and Gault formula).
  16. Any current cardiovascular disease or abnormality on 12-lead ECG at screening that, in the investigator's opinion, is clinically significant and could be a potential safety risk to the participant, including risk factors for stroke (e.g., atrial fibrillation, cardiomyopathy).
  17. History of cancer (currently active or in remission) within 5 years prior to screening, excluding treated basal or squamous skin cancer, or stable prostate cancer.
  18. Lack of reliable venous access for the weekly administration of study drug.
  19. Contraindications to the lumbar puncture (LP) procedure such as prior lumbosacral spine surgery, severe degenerative joint disease or deformity of the spine, platelet count < 100,000, use of an anticoagulant (e.g., warfarin), or history of a bleeding disorder.
  20. Any current psychiatric or neurological disorder other than AD that, in the investigator's opinion, may interfere with the participant's ability to provide informed consent or appropriately complete the study's safety or efficacy assessments.
  21. Significant suicide risk as indicated by a "yes" response to #4 or #5 under Suicidal Ideation or any "yes" response under Suicidal Behavior on the Columbia Suicide Severity Rating Scale (C-SSRS) during the screening visit.
  22. Any other medical condition or abnormal finding during screening that, in the investigator's opinion, could confound collection or interpretation of safety or efficacy data or be a potential safety risk to the participant.

Sites / Locations

  • Austin Health
  • Goulburn Valley Health
  • Neurodegenerative Disorders Research Pty Ltd

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

SLS-005 - Once Weekly

SLS-005 - Twice Weekly

Arm Description

SLS-005 (trehalose injection, 90.5 mg/mL for intravenous infusion). SLS-005 will be administered as a weight-based dose of 0.75 g/kg by IV infusion once a week over 60 ± 5 minutes for volumes <600 mL or 90 minutes +5 min for volumes >600 mL. For 52 weeks.

SLS-005 (trehalose injection, 90.5 mg/mL for intravenous infusion). SLS-005 will be administered as a weight-based dose of 0.75 g/kg by IV infusion twice a week over 60 ± 5 minutes for volumes <600 mL or 90 minutes +5 min for volumes >600 mL. For 52 weeks.

Outcomes

Primary Outcome Measures

Endpoints for Safety and Tolerability of Treatment
Incidences of treatment-emergent Adverse Events and Serious Adverse Events (SAEs), including clinically significant laboratory and electrocardiogram (ECG) abnormalities
Endpoints for Safety and Tolerability of Treatment
Incidences of treatment-emergent early study and treatment discontinuations.

Secondary Outcome Measures

Endpoints for Treatment Effects on Imaging Biomarkers Associated with AD
Changes in brain imaging biomarkers associated with AD
Endpoints for Treatment Effects on CSF Biomarkers Associated with AD
Changes in CSF biomarkers associated with AD
Endpoints for Treatment Effects on Volumes of Brain Structures
Changes in the volumes of specified brain structures as measured by brain MRI
Exploratory Endpoints - Treatment Effects in Cognitive Performance
Changes from baseline in cognitive performance as measured by the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog 13). ADAS-Cog 13 is a series of questions to the participant and tasks for the participant to perform. It is used to measure cognitive functions and non-cognitive functions such as mood and behaviour
Exploratory Endpoints - Treatment Effects in Dementia Severity
Changes from baseline in dementia severity as measured by the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB). The CDR-SB is a semi structured interview with the participants caregiver, used to asses the severity of the symptoms of dementia.
Exploratory Endpoints - Treatment Effects in Activities of Daily Living
Changes from baseline in functioning in activities of daily living (ADL) as measured by the Alzheimer's Disease Cooperative Study - instrumental Activities of Daily Living (ADCS-iADL). The scale is used to assess functional decline in participants. The participants study partner is asked questions about the participants activities of daily living.
Exploratory Endpoints - Treatment Effects in Behavioral Symptoms and Functioning
Changes from baseline in behavioral symptoms and functioning as measured by the Neuropsychiatric Inventory (NPI). The purpose of the NPI is to obtain information on the presence of psychopathology in patients with brain disorders.The participants caregiver is asked questions in an interview to evaluate the participants behaviour.
Exploratory Endpoints - Treatment Effects in Cognitive Impairment
Change from baseline in Mini-mental status examination (MMSE). The rater will ask the participant a series of questions and ask the participants to perform some tasks. It used to assess cognitive impairment.

Full Information

First Posted
March 25, 2022
Last Updated
April 10, 2023
Sponsor
Seelos Therapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05332678
Brief Title
SLS-005 (Trehalose Injection) in the Treatment of Alzheimer's Disease
Acronym
[STRIVE-AD]
Official Title
An Open-Label, Proof-of-Concept Study to Evaluate the Safety and Treatment Effects of SLS-005 (Trehalose Injection, 90.5 mg/mL for Intravenous Infusion) in Participants With Alzheimer's Disease (AD)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Withdrawn
Why Stopped
Sponsor Decision
Study Start Date
March 3, 2023 (Actual)
Primary Completion Date
April 10, 2023 (Actual)
Study Completion Date
April 10, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Seelos Therapeutics, Inc.

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
An open-label, proof-of-concept study to evaluate the safety and treatment effects of SLS-005 in Participants with Alzheimer's Disease (AD) treated once or twice weekly for 52 weeks.
Detailed Description
This is an open-label proof-of-concept study to evaluate the safety and treatment effects of SLS-005 (trehalose injection, 90.5 mg/mL for intravenous infusion) administered by IV infusion in either a once weekly or twice weekly dosing regimen in eligible men and women, ages 50-85 years, who have very mild, mild, or moderate dementia as determined by the Clinical Dementia Rating (CDR) global score and a biomarker-supported diagnosis of AD guided by the National Institute on Aging and Alzheimer's Association (NIA-AA) Research Framework. The study will enroll approximately 30 eligible participants who will be assigned in a 1:1 ratio to treatment with SLS-005 at a dose of 0.75 g/kg. administered by intravenous (IV) infusion in either a once weekly or twice weekly dosing regimen for up to 52 weeks. Participants will be assigned to 1 of the 2 dosing regimens to achieve approximately equal numbers of participants with mild (CDR 0.5 or 1) and moderate (CDR 2) baseline dementia severity in each dosing regimen. A relatively equal number of participants enrolled in each dosing regimen will be assigned to either the amyloid or tau PET procedure. Tracers to be used will be approved by Sponsor and described in the imaging manual. Adverse events and results of laboratory and physical evaluations will be collected and assessed throughout the study. Fluid biomarkers associated with AD pathology, brain imaging including amyloid or tau PET and volumetric magnetic resonance imaging (MRI), and measures of cognitive performance, functioning in activities of daily living (ADL), and neuropsychiatric behavioral symptoms will be collected at baseline and at scheduled times throughout the study. Participants who terminate treatment early, will be encouraged to complete all safety and outcome procedures as specified in the protocol's schedule of events.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer's Disease
Keywords
Trehalose, Phase II, Dementia, Australia, SLS-005, STRIVE-AD

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
SLS-005 - Once Weekly
Arm Type
Experimental
Arm Description
SLS-005 (trehalose injection, 90.5 mg/mL for intravenous infusion). SLS-005 will be administered as a weight-based dose of 0.75 g/kg by IV infusion once a week over 60 ± 5 minutes for volumes <600 mL or 90 minutes +5 min for volumes >600 mL. For 52 weeks.
Arm Title
SLS-005 - Twice Weekly
Arm Type
Experimental
Arm Description
SLS-005 (trehalose injection, 90.5 mg/mL for intravenous infusion). SLS-005 will be administered as a weight-based dose of 0.75 g/kg by IV infusion twice a week over 60 ± 5 minutes for volumes <600 mL or 90 minutes +5 min for volumes >600 mL. For 52 weeks.
Intervention Type
Drug
Intervention Name(s)
SLS-005 - Once Weekly
Other Intervention Name(s)
SLS-005
Intervention Description
Please see Arm description.
Intervention Type
Drug
Intervention Name(s)
SLS-005 - Twice Weekly
Other Intervention Name(s)
SLS-005
Intervention Description
Please see Arm description.
Primary Outcome Measure Information:
Title
Endpoints for Safety and Tolerability of Treatment
Description
Incidences of treatment-emergent Adverse Events and Serious Adverse Events (SAEs), including clinically significant laboratory and electrocardiogram (ECG) abnormalities
Time Frame
over 52 week treatment period
Title
Endpoints for Safety and Tolerability of Treatment
Description
Incidences of treatment-emergent early study and treatment discontinuations.
Time Frame
52 weeks
Secondary Outcome Measure Information:
Title
Endpoints for Treatment Effects on Imaging Biomarkers Associated with AD
Description
Changes in brain imaging biomarkers associated with AD
Time Frame
26 and 52 weeks
Title
Endpoints for Treatment Effects on CSF Biomarkers Associated with AD
Description
Changes in CSF biomarkers associated with AD
Time Frame
26 and 52 weeks
Title
Endpoints for Treatment Effects on Volumes of Brain Structures
Description
Changes in the volumes of specified brain structures as measured by brain MRI
Time Frame
26 and 52 weeks
Title
Exploratory Endpoints - Treatment Effects in Cognitive Performance
Description
Changes from baseline in cognitive performance as measured by the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog 13). ADAS-Cog 13 is a series of questions to the participant and tasks for the participant to perform. It is used to measure cognitive functions and non-cognitive functions such as mood and behaviour
Time Frame
13, 26, 39 and 52 weeks
Title
Exploratory Endpoints - Treatment Effects in Dementia Severity
Description
Changes from baseline in dementia severity as measured by the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB). The CDR-SB is a semi structured interview with the participants caregiver, used to asses the severity of the symptoms of dementia.
Time Frame
13, 26, 39 and 52 weeks
Title
Exploratory Endpoints - Treatment Effects in Activities of Daily Living
Description
Changes from baseline in functioning in activities of daily living (ADL) as measured by the Alzheimer's Disease Cooperative Study - instrumental Activities of Daily Living (ADCS-iADL). The scale is used to assess functional decline in participants. The participants study partner is asked questions about the participants activities of daily living.
Time Frame
13, 26, 39 and 52 weeks
Title
Exploratory Endpoints - Treatment Effects in Behavioral Symptoms and Functioning
Description
Changes from baseline in behavioral symptoms and functioning as measured by the Neuropsychiatric Inventory (NPI). The purpose of the NPI is to obtain information on the presence of psychopathology in patients with brain disorders.The participants caregiver is asked questions in an interview to evaluate the participants behaviour.
Time Frame
13, 26, 39 and 52 weeks
Title
Exploratory Endpoints - Treatment Effects in Cognitive Impairment
Description
Change from baseline in Mini-mental status examination (MMSE). The rater will ask the participant a series of questions and ask the participants to perform some tasks. It used to assess cognitive impairment.
Time Frame
26 and 52 Weeks.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Have a study partner/caregiver who, in the Investigator's judgment, has frequent and sufficient face-to-face contact with the participant (approximately 10 hours per week or more) and consents to attend all study visits, assist in ensuring compliance with all study requirements and procedures, and provide input into assessments of cognitive performance and functioning in daily activities throughout the full duration of the participant's involvement in the study. Signed informed consent from: The participant or person responsible/guardian The participant's study partner/caregiver Men and women, 50 to 85 years (inclusive) of age. Gradual and progressive change in cognitive performance has been observed for ≥ 6 months not associated with a specific event or medical condition e.g., head trauma, stroke, cardiac arrest, cerebrovascular disease, epilepsy, alcohol abuse, etc. Capable of completing study assessments either alone or with assistance from the study partner. Mini-mental status examination (MMSE) score ≥ 16 and ≤ 27 at screening. Modified Hachinski Score ≤ 4 at screening. Body Mass Index (BMI) between 20 kg/m2 and 32 kg/m2 (inclusive) Clinical Dementia Rating (CDR) global score of 0.5, 1.0, or 2.0 at screening. Clinical Dementia Rating - Sum of Boxes (CDR-SB) score ≥ 0.5 at screening. Documentation of results for either CSF Aβ42, CSF Aβ42/Aβ40 ratio, or brain imaging with PET (amyloid or tau) that was consistent with a diagnosis of AD within 12 months of screening. Stable doses of all concomitant medications for at least 30 days prior to the baseline visit. For participants taking cholinesterase inhibitors and/or memantine, documentation of stable use for at least 12 weeks is required prior to screening. Negative serum beta-human chorionic gonadotropin (ß-hCG) pregnancy result at the screening visit for female participants of childbearing potential. Willingness to comply with sexual abstinence or contraception guidelines of this study. Willingness and ability to complete all study procedures, including brain magnetic resonance imaging (MRI), lumbar puncture, clinical genotyping, and brain positron emission tomography (PET). Participant and study partner/caregiver must be fluent in the English language for both reading and speaking. Participant and study partner/caregiver must be fully vaccinated as per local regulations for COVID-19 at least 2 weeks prior to screening. Exclusion Criteria Presence of a neurologic or neuropsychiatric condition or imaging finding associated with a neurologic or neuropsychiatric condition other than AD that can be associated with dementia or confound the evaluation of dementia, including but not limited to Parkinson's disease, Huntington's disease, frontotemporal dementia, cerebrovascular disease, (diseases related to or events associated with disruption of blood flow to the brain), seizure disorders, inflammatory or infectious disorders of the central nervous system, normal pressure hydrocephalus, traumatic brain injury, uncontrolled major depression, psychosis, bipolar disorder, and long-term sequelae of alcohol or substance abuse. History of stroke or transient ischemic attack (TIA) within 12 months of screening. Epileptic or epileptiform seizure within 12 months of screening. Current participation in another clinical trial or completed participation in an interventional trial less than 30 days prior to the screening visit (90 days for a biological treatment). Involvement in an Aβ or tau vaccination trial for AD unless known to have received only placebo. Current diagnosis and/or healthcare professional-recommended treatment (medication and/or diet) of diabetes mellitus type 1 or type 2. Hemoglobin A1c (HbA1c) ≥ 6.5% at the screening visit Prior treatment with SLS-005, any other IV trehalose formulation, or known hypersensitivity to trehalose. Is receiving aducanumab or any other immunotherapy for treatment of dementia including AD. Regular use (≥ 3 days per week) of prescribed or pharmacy-purchased opiates, opioids, or benzodiazepines. Pregnant or breastfeeding. History of alcohol or drug abuse within the last 2 years. Chronic liver disease including Hepatitis B; Hepatitis C unless successful curative treatment is documented; human immunodeficiency virus (HIV) infection. Prior history of drug-induced liver injury (DILI) and/or laboratory results at screening that indicate inadequate liver function (e.g., alanine aminotransferase [ALT], aspartate aminotransferase [AST], gamma-glutamyl transferase [GGT] > 2 times the upper limit of normal [x ULN] and/or total bilirubin level > 2 x ULN). Laboratory results at screening that indicate inadequate renal function (e.g., estimated creatinine clearance of < 60 mL/min calculated by the Cockcroft and Gault formula). Recent history of heart failure or unexplained edema or any current cardiovascular disease or abnormality on 12-lead ECG at screening that, in the investigator's opinion, is clinically significant and could be a potential safety risk to the participant, including risk factors for stroke (e.g., atrial fibrillation, cardiomyopathy). History of cancer (currently active or in remission) within 5 years prior to screening, excluding treated basal or squamous skin cancer, or stable prostate cancer. Lack of reliable venous access for the weekly administration of study drug. Contraindications to the lumbar puncture (LP) procedure such as prior lumbosacral spine surgery, severe degenerative joint disease or deformity of the spine, platelet count < 100,000, use of an anticoagulant (e.g., warfarin), or history of a bleeding disorder. Any current psychiatric or neurological disorder other than AD that, in the investigator's opinion, may interfere with the participant's ability to provide informed consent or appropriately complete the study's safety or efficacy assessments. Significant suicide risk as indicated by a "yes" response to #4 or #5 under Suicidal Ideation or any "yes" response under Suicidal Behavior on the Columbia Suicide Severity Rating Scale (C-SSRS) during the screening visit. Any other medical condition or abnormal finding during screening that, in the investigator's opinion, could confound collection or interpretation of safety or efficacy data or be a potential safety risk to the participant.
Facility Information:
Facility Name
Austin Health
City
Heidelberg
State/Province
Victoria
ZIP/Postal Code
3084
Country
Australia
Facility Name
Goulburn Valley Health
City
Shepparton
State/Province
Victoria
ZIP/Postal Code
3630
Country
Australia
Facility Name
Neurodegenerative Disorders Research Pty Ltd
City
West Perth
State/Province
Western Australia
ZIP/Postal Code
6005
Country
Australia

12. IPD Sharing Statement

Plan to Share IPD
No

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SLS-005 (Trehalose Injection) in the Treatment of Alzheimer's Disease

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