Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001755820
Ethics application status
Approved
Date submitted
27/10/2021
Date registered
22/12/2021
Date last updated
22/12/2021
Date data sharing statement initially provided
22/12/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
A 24-week Open Label, Basket Study of SLS-005 (Trehalose Injection 90.5 mg/mL Intravenous Infusion) in the Treatment of Adults with Neurodegenerative Diseases.
Scientific title
A 24-week Open Label, Basket Study of the safety, tolerability and treatment responses of SLS-005 (Trehalose Injection 90.5 mg/mL Intravenous Infusion) in Adults with Neurodegenerative Diseases
Secondary ID [1] 305491 0
SLS-005-204
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Amyotrophic Lateral Sclerosis (ALS) 323879 0
Huntington’s Disease (HD) 323880 0
Spinocerebellar Ataxia Type-3 (SCA3). 323881 0
Condition category
Condition code
Neurological 321392 321392 0 0
Neurodegenerative diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
SLS-005-204 is an open-label basket study of SLS-005 (trehalose injection, 90.5 mg/mL for intravenous infusion) for treatment of adults with selected neurodegenerative diseases characterized by accumulation of abnormal protein aggregates. The study plans to enroll 15 to 18 participants comprised of up to 4 participants with amyotrophic lateral sclerosis (ALS), up to 10 participants with Huntington’s disease (HD), and up to 4 participants with spinocerebellar ataxia type-3 (SCA3).
The study consists of a 2-week screening period, a 24-week open-label treatment period, and a 2-week safety follow-up period. Eligible participants will receive SLS-005 administered as a once weekly intravenous infusion at a dose of 0.75 g/kg over 60 minutes for volumes less than or equal to 600 mL or 90 minutes for volumes greater than 600mL over a treatment period of 24 weeks. The total volume of the infusion will be based on participant weight and dose of 0.75 g/kg.

An additional 52 weeks of open-label SLS-005 treatment is planned for consenting participants who are determined to be medically appropriate after their completion of the primary 24-week open-label treatment period.

The clinical facility staff will administer each study treatment at the study centre. First patient doses will be witnessed by a Sponsor representative to ensure adherence to the administration procedure outlined in the study protocol. Investigational product dispensing and administration will also be documented as per study guidelines which will be monitored, and accountability assessed by Sponsor representatives.
Intervention code [1] 321919 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 329164 0
Determine the safety and tolerability of SLS-005 in participants with selected neurodegenerative diseases (ALS, HD and SCA3) assessed by incidences of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), clinically significant laboratory or diagnostic testing abnormalities, vital signs (blood pressure, heart rate, respiration rate, and body temperature), and ECGs. Blood pressure is measured using an electronic blood pressure monitor which will also display heart rate in beats per minute, respiration rate is counted manually as breaths per, body temperature measured using an oral thermometer. Laboratory abnormalities are assessed by analysis of blood and urine samples (haematology, chemistry panels and urinalysis).
Adverse events (AEs) and Serious Adverse Events (SAEs) will be assessed for severity and causality (relationship of the event to the investigational product by the study investigator using the specified grading definitions Common Terminology Criteria for Adverse Events (CTCAE5.0) as outlined in the study protocol. These assessments will also be reviewed by study medical monitors.
Timepoint [1] 329164 0
The study participants will be assessed for the outcome at the following timepoints:
Adverse events: Continuously throughout the 24-week study period.
Laboratory abnormalities (Haematology, Chemistry, Urinalysis): Weeks 4, 12 and 24 post-intervention commencement.
Physical examinations: Weeks 12 and 24 post-intervention commencement,
ECG: Weeks 4, 12 & 24 post-intervention commencement
Vital Signs: Day 1 and then weekly throughout the 24-week study period.
Primary outcome [2] 329169 0
Determine treatment response rate of SLS-005 in participants with selected neurodegenerative diseases (i.e., ALS, HD and SCA3) using physician and patient-reported outcome measures i.e. treatment response assessed using change on the Patient Global Impression of Change (PGIC) scale and the Clinical Global Impression of Change (CGIC) scale from baseline. Treatment Response Rate Participant (TRR-P) at week 24 [Percentage of participants reporting a treatment response defined as improvement or no change from baseline on the Patient Global Impression of Change (PGIC)]
Timepoint [2] 329169 0
Patient Global Impression of Change (PGIC) and Clinical Global Impression of Change (CGIC) are completed at Weeks 4, 8, 12, 18 & 24 post-intervention commencement.


Secondary outcome [1] 401711 0
Determine the effectiveness of SLS-005 on disease progression and severity in participants with selected neurodegenerative diseases using clinician and patient-reported outcome measures assessed by Change from baseline in Patient Global Impression of Severity (PGIS)
Timepoint [1] 401711 0
The study participants will be assessed for this outcome on Weeks 4, 8, 12, 18 and 24 post-intervention commencement
Secondary outcome [2] 404063 0
Determine the effectiveness of SLS-005 on disease progression and severity in participants with selected neurodegenerative diseases using clinician and patient-reported outcome measures assessed by Change from baseline in Clinical Global Impression of Severity (CGIS)
Timepoint [2] 404063 0
The study participants will be assessed for this outcome on Weeks 4, 8, 12, 18 and 24 post-intervention commencement
Secondary outcome [3] 404064 0
Determine the effectiveness of SLS-005 on disease progression and severity in participants with selected neurodegenerative diseases using clinician and patient-reported outcome measures assessed by Change from baseline in EuroQol visual analogue scale (EQ VAS) score
Timepoint [3] 404064 0
The study participants will be assessed for this outcome on Weeks 4, 8, 12, 18 and 24 post-intervention commencement
Secondary outcome [4] 404065 0
Determine the effectiveness of SLS-005 on disease progression and severity in participants with selected neurodegenerative diseases using clinician and patient-reported outcome measures assessed by Change from baseline in disease specific scale scores for Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), the Center for Neurologic Study Bulbar Function Scale (CNS-BFS) in participants with Amyotrophic Lateral Sclerosis (ALS)
Timepoint [4] 404065 0
The study participants will be assessed for this outcome on Weeks 4, 8, 12, 18 and 24 post-intervention commencement
Secondary outcome [5] 404066 0
Determine the effectiveness of SLS-005 on disease progression and severity in participants with selected neurodegenerative diseases using clinician and patient-reported outcome measures assessed by Change from baseline in disease specific scale scores for Unified Huntington Disease Rating Scale (UHDRS) – Total Functional Capacity (TFC) and Independence Scale in participants with Huntington Disease (HD)
Timepoint [5] 404066 0
The study participants will be assessed for this outcome on Weeks 4, 8, 12, 18 and 24 post-intervention commencement
Secondary outcome [6] 404069 0
Determine the effectiveness of SLS-005 on disease progression and severity in participants with selected neurodegenerative diseases using clinician and patient-reported outcome measures assessed by Change from baseline in slow vital capacity (SVC) for participants with ALS at weeks 4, 8, 12, 18 and 24. Spirometry equipment will be used for SVC assessment and analysis will include SVC, predicted SVC, and % of predicted SVC.
Timepoint [6] 404069 0
The study participants will be assessed for this outcome on Weeks 4, 8, 12, 18 and 24 post-intervention commencement

Eligibility
Key inclusion criteria
1. Men and women, 18 - 75 years (inclusive) of age at screening
2. Signed informed consent
3. Must meet the disease specific criteria for ALS, SCA or HD listed below:
a) ALS:
-Diagnosis of probable, lab-supported probable, or definitive ALS
-Onset of signs and symptoms of disease within the past 2 years
-Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score greater than 30 at the screening visit
-Slow Vital Capacity (SVC) greater than 50% of predicted for gender, height, and age at the screening visit
b)HD:
-Clinical diagnosis of HD with documented genetic confirmation
-Onset of signs and symptoms of disease within the past 2 years and onset between the ages of 18 and 50 years (inclusive)
-Unified Huntington's Disease Rating Scale (UHDRS)-Total Functional Capacity (TFC) score of 7 to 13 (inclusive) at the screening visit
-Body Mass Index (BMI) between 20 kg/m2 and 32 kg/m2 (inclusive)
c)SCA3:
-Clinical diagnosis of SCA3 with documented genetic confirmation
-Modified scale for assessment and rating of ataxia (m-SARA) total score greater than 4 at the screening visit.
-m-SARA gait component score greater than 1 at the screening visit.
5. Stable doses of all concomitant medications for 30 days prior to study entry and agree to remain on stable doses for the duration of the study.
6. Negative serum beta-human chorionic gonadotropin (ß-hCG) pregnancy result at the screening visit for female participants of childbearing potential
7. Willingness to comply with sexual abstinence or contraception guidelines of this study
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. 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).
2. History of gene therapy, cell transplants, or brain surgery aimed at treating the medical condition of interest within 1 year of the screening visit.
3. Prior treatment with SLS-005, any other intravenous trehalose formulation, or known hypersensitivity to trehalose.
4. Current diagnosis and/or healthcare professional-recommended treatment (medication and/or diet) of diabetes mellitus type 1 or type 2.
5. HbA1c greater than or equal to 6.5% at the screening visit
6. Pregnant or breastfeeding.
7. History of alcohol or drug abuse within the last 2 years.
8. Chronic liver disease including Hepatitis B; Hepatitis C unless successful curative treatment is documented; human immunodeficiency virus (HIV) infection.
9. Prior history of drug-induced liver injury (DILI) and/or laboratory results at screening that indicate inadequate liver function
10. Laboratory results at screening that indicate inadequate renal function
11. Any current cardiovascular disease or abnormality on 12-lead electrocardiogram (ECG) at screening that, in the investigator’s opinion, is clinically significant and could be a potential safety risk to the participant.
12. Any current psychiatric, neurological, or cognitive disorder 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.
13. 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.
14. 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
30/12/2021
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/09/2022
Actual
Sample size
Target
18
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 20701 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 20954 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 35503 0
2050 - Camperdown
Recruitment postcode(s) [2] 35781 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 309852 0
Commercial sector/Industry
Name [1] 309852 0
Seelos Therapeutics Australia Pty Ltd (Seelos Therapeutics, Inc)
Country [1] 309852 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Avance Clinical
Address
Level 1, 2 Ann Nelson Drive, Thebarton, SA, 5042
Country
Australia
Secondary sponsor category [1] 310887 0
None
Name [1] 310887 0
Address [1] 310887 0
Country [1] 310887 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309589 0
Sydney Local Health District Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 309589 0
Ethics committee country [1] 309589 0
Australia
Date submitted for ethics approval [1] 309589 0
27/09/2021
Approval date [1] 309589 0
22/11/2021
Ethics approval number [1] 309589 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 114690 0
Prof Matthew Kiernan
Address 114690 0
Royal Prince Alfred Hospital
Missenden Road
Camperdown NSW 2050 AUSTRALIA
Country 114690 0
Australia
Phone 114690 0
+61 2 9114 4250
Fax 114690 0
+61 2 9114 4254
Email 114690 0
[email protected]
Contact person for public queries
Name 114691 0
Matthew Kiernan
Address 114691 0
Royal Prince Alfred Hospital
Missenden Road
Camperdown NSW 2050 AUSTRALIA
Country 114691 0
Australia
Phone 114691 0
+61 2 9114 4250
Fax 114691 0
+61 2 9114 4254
Email 114691 0
[email protected]
Contact person for scientific queries
Name 114692 0
Timothy Whitaker
Address 114692 0
Seelos Therapeutics, Inc.
300 Park Avenue, New York, NY 10022
Country 114692 0
United States of America
Phone 114692 0
+1 646 2412111
Fax 114692 0
Email 114692 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Privacy and intellectual property considerations


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.