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

Sponsor

Neuroscience Trials Australia (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05332678

Collaborator

Seelos Therapeutics, Inc. (Industry)

Enrollment

Locations

Arms

Anticipated Duration (Months)

13.3

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Phase II, randomized, double-blind, placebo-controlled study to evaluate the treatment effects and safety of SLS-005 in Participants with Alzheimer's Disease (AD) treated weekly for 52 weeks.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer's Disease	Drug: SLS-005 Drug: Placebo	Phase 2

Detailed Description

This is a randomized, double-blind, placebo-controlled, proof-of-concept study evaluating the treatment effects and safety of SLS-005 (trehalose injection, 90.5 mg/mL for intravenous infusion) 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 that, at a minimum, must include reliable documentation of previous results for either CSF Aβ42, CSF Aβ42/Aβ40 ratio, or brain imaging with either amyloid or tau positron emission tomography (PET) that was consistent with a diagnosis of AD within 12 months of screening.

The study will enroll approximately 40 eligible participants who will be randomized in a 3:1 ratio to treatment with either SLS-005 at a dose of 0.75 g/kg or equivalent placebo (sodium chloride injection, 0.9%, USP) administered by intravenous (IV) infusion once every week for up to 52 weeks. Participant randomization assignments will be stratified by baseline dementia severity (i.e., mild (CDR 0.5 or 1), or moderate (CDR 2)) using a single fixed randomization scheme with stratified, randomly permuted blocks. Relatively equal number of enrolled participants in each treatment group within the stratified cohort will be assigned either the amyloid (18F florbetapir) or tau (18F flortaucipir) PET.

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Treatment Effects and Safety of SLS-005 (Trehalose Injection, 90.5 mg/mL for Intravenous Infusion) in Participants With Alzheimer's Disease (AD)

Anticipated Study Start Date :

Aug 1, 2022

Anticipated Primary Completion Date :

Sep 1, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SLS-005 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.	Drug: SLS-005 Please see Arm description.
Placebo Comparator: Placebo Placebo (sodium chloride injection, 0.9%, USP) will be administered as a weight-based volume equivalent to a SLS-005 0.75 g/kg dose calculation 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.	Drug: Placebo Please see Arm description.

Arm

Intervention/Treatment

Experimental: SLS-005

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.

Drug: SLS-005

Please see Arm description.

Placebo Comparator: Placebo

Placebo (sodium chloride injection, 0.9%, USP) will be administered as a weight-based volume equivalent to a SLS-005 0.75 g/kg dose calculation 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.

Drug: Placebo

Please see Arm description.

Outcome Measures

Primary Outcome Measures

Endpoints for Treatment Effects on AD Biomarkers [26 weeks]
Changes in brain imaging biomarkers associated with AD
Endpoints for Treatment Effects on AD Biomarkers [52 weeks]
Changes in brain imaging biomarkers associated with AD

Secondary Outcome Measures

Endpoints for Safety and Tolerability of Treatment [over 52 week treatment period]
Incidences of treatment-emergent Adverse Events and Serious Adverse Events (SAEs), including clinically significant laboratory and electrocardiogram (ECG) abnormalities
Exploratory Endpoints [Over 52 week period.]
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 [Over 52 week period.]
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 [Over 52 week period.]
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 [Over 52 week period.]
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 [At 26 Weeks.]
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.
Exploratory Endpoints [At 52 Weeks.]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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, 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).
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ausin Health	Heidelberg	Victoria	Australia	3084
2	Goulburn Valley Health	Shepparton	Victoria	Australia	3630
3	Neurodegenerative Disorders Research Pty Ltd	West Perth	Western Australia	Australia	6005