Triumeq in Amyotrophic Lateral Sclerosis (LIGHTHOUSE II)
Primary Purpose
Amyotrophic Lateral Sclerosis
Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Dolutegravir, Abacavir and Lamivudine
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Amyotrophic Lateral Sclerosis focused on measuring ALS
Eligibility Criteria
Inclusion Criteria:
- Age ≥ 18 years at the time of screening
- Diagnosis of ALS according to the Gold Coast Criteria
- Capable of providing informed consent and complying with trial procedures
- TRICALS risk profile > -6.0 and < -2.0
- Those taking Riluzole must be on a stable dose for at least 30 days prior to the baseline visit or must have stopped taking Riluzole at least 30 days prior to the baseline visit
- Women must not become pregnant (e.g., post-menopausal, surgically sterile, using highly effective birth control methods or not having potentially reproductive sex) for the duration of the study. Highly effective methods of birth control are those with a failure rate of < 1% per year when employed consistently and correctly, e.g. Combined (oestrogen and progestogen containing) hormonal contraception or progestogen-only hormonal contraception
- Women of childbearing potential must have a negative serum pregnancy test at screening and baseline and be non-lactating. Women of childbearing potential are defined as females who have experienced menarche and are not surgically sterilised (e.g. hysterectomy or bilateral salpingectomy) or post-menopausal (defined as at least 1 year since last regular menstrual period).
- For participants taking antacids (regularly or as required), participant is willing and able to avoid taking antacids for at least 2 hours before and 6 hours after Triumeq
Exclusion Criteria:
- People who are HLA-B*5701 positive
- Known hypersensitivity to Dolutegravir, Abacavir or Lamivudine, or to any of the excipients
Safety Laboratory Criteria at screening:
- ALT ≥ 5 times upper limit of normal (ULN)
- AST ≥ 3 times ULN
- Bilirubin ≥ 1.5 times ULN
- Creatinine clearance < 30 mL / min
- Platelet concentration of < 100 x109 per L
- Absolute neutrophil count of < 1x109 per L
- Haemoglobin < 100 g/L
- Amylase & lipase ≥ 2 times ULN
- Lactate ≥ 2 times ULN
- Moderate to severe hepatic impairment, as defined by local clinical guidelines
- Presence of HIV antibodies at screening
- Presence of Hepatitis C antibodies at screening unless participants have had effective treatment for Hepatitis C
- Presence of Hepatitis B core or surface antigen at screening
- Participation in any other investigational drug trial or using investigational drug within 30 days prior to screening
- Use of NIV ≥22 h per day or having a tracheostomy
- Edaravone dose within 30 days prior to screening. Edaravone is approved by the FDA and in Japan, but remains an investigational product in Europe and Australia
- Clinically significant history of unstable or severe cardiac, oncological, psychiatric, hepatic, or renal disease or other medically significant illness
- Taking medication contraindicated with Triumeq: Dofetilideor Fampridine (dalfampridine)
Sites / Locations
- The University of Sydney - Brain and Mind CentreRecruiting
- MQ Health NeurologyRecruiting
- Sunshine Coast University HospitalRecruiting
- Royal Brisbane and Women's HospitalRecruiting
- Flinders Medical CentreRecruiting
- Launceston General HospitalRecruiting
- Calvary Health Care BethlehemRecruiting
- The Perron InstituteRecruiting
- Christchurch HospitalRecruiting
- Clinical Trials Unit, Tauranga HospitalRecruiting
- Wellington Regional HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Dolutegravir/Abacavir/Lamivudine
Placebo
Arm Description
Combination of Dolutegravir, Abacavir and Lamivudine in a single product/capsule. 4 capsules to be taken orally once daily (all 4 at the same time, each capsule is Dolutegravir 12.5mg, Abacavir 150mg and Lamivudine 75mg). Maximum duration is 24months
4 capsules to be taken orally once daily (all 4 at the same time). Maximum duration is 24months
Outcomes
Primary Outcome Measures
Measure overall survival at 24 months or after a minimum of 212 events
Overall survival is measured as death from any cause, in participants with ALS at 24 months, or after a minimum of 212 events.
Secondary Outcome Measures
Measure scoring in the ALS-Functional Rating Scale Revised (ALSFRS-R) at 3 monthly intervals.
The ALSFRS-R is a 12 item participant self-report measure that monitors ALS disease progression, where a higher score reflects a better outcome.
Number of participants with abnormal Slow Vital Capacity measured by hand spirometry at 3 monthly intervals
Slow vital capacity is measured in litres, and as a % of predicted.
Measure plasma creatinine at 3 monthly intervals
Plasma creatinine is assessed to monitor kidney function
Assign a value using the King's Staging Scale to describe degree of disease advancement over time
The King's Staging Scale is a clinical staging system defining four stages of ALS assessed by way of a semi-structured interview with the participant.
Evaluate the incidence of treatment-emergent adverse events
based on physical examinations and patient reported symptoms.
Measure study medication discontinuation
the number of participants who discontinue study medication will be assessed to assess tolerability
Measure the score obtained with the Edinburgh Cognitive and Behavioural Assessment Screen (ECAS)
ECAS is a multidomain assessment questionnaire used in ALS to assess cognitive and behavioural changes where a higher score relates to a better outcome.
Measure the responses in the EQ-5D-5L quality of life health questionnaire.
The EQ-5D-5L questionnaire is a standardised measure of health-related Quality of Life, also incorporating a Visual Analogue Scale. A higher score relates to a better outcome.
Measurement of several biomarkers from blood and urine samples
Urinary P75ECD, plasma neurofilament light and heavy chain, HERV-K expression and genotyping (UNC13a / C9orf72) will be measured for post-trial exploratory analyses.
Full Information
NCT ID
NCT05193994
First Posted
December 6, 2021
Last Updated
June 9, 2023
Sponsor
Macquarie University, Australia
Collaborators
King's College London, Stichting TRICALS Foundation
1. Study Identification
Unique Protocol Identification Number
NCT05193994
Brief Title
Triumeq in Amyotrophic Lateral Sclerosis
Acronym
LIGHTHOUSE II
Official Title
Randomised Double-Blind Placebo-Controlled Phase 3 Trial of Triumeq in Amyotrophic Lateral Sclerosis
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 24, 2022 (Actual)
Primary Completion Date
December 1, 2025 (Anticipated)
Study Completion Date
July 1, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Macquarie University, Australia
Collaborators
King's College London, Stichting TRICALS Foundation
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
To determine if Triumeq improves survival in Amyotrophic Lateral Sclerosis (ALS) compared with placebo
Detailed Description
This Randomised Double-Blind Placebo Controlled trial seeks to investigate whether the combination medicine Triumeq (dolutegravir 50mg, abacavir 600mg, lamivudine 300mg), already sold in Australia for HIV treatment is effective in delaying progression of theAmyotrophic Lateral Sclerosis (ALS) disease and if it is safe and well tolerated in patients with ALS. This medication is very commonly prescribed for patients with HIV. The secondary aim of this study is to assess patient's health outcomes whilst taking this medication for their ALS.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Amyotrophic Lateral Sclerosis
Keywords
ALS
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Participants will be randomised in a 2:1 ratio to receive either triumeq or placebo
Masking
ParticipantInvestigator
Masking Description
Double-blind
Allocation
Randomized
Enrollment
390 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Dolutegravir/Abacavir/Lamivudine
Arm Type
Experimental
Arm Description
Combination of Dolutegravir, Abacavir and Lamivudine in a single product/capsule.
4 capsules to be taken orally once daily (all 4 at the same time, each capsule is Dolutegravir 12.5mg, Abacavir 150mg and Lamivudine 75mg). Maximum duration is 24months
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
4 capsules to be taken orally once daily (all 4 at the same time). Maximum duration is 24months
Intervention Type
Drug
Intervention Name(s)
Dolutegravir, Abacavir and Lamivudine
Other Intervention Name(s)
Triumeq
Intervention Description
Dolutegravir 50mg, Abacavir 600mg and Lamivudine 300mg.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo.
Primary Outcome Measure Information:
Title
Measure overall survival at 24 months or after a minimum of 212 events
Description
Overall survival is measured as death from any cause, in participants with ALS at 24 months, or after a minimum of 212 events.
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Measure scoring in the ALS-Functional Rating Scale Revised (ALSFRS-R) at 3 monthly intervals.
Description
The ALSFRS-R is a 12 item participant self-report measure that monitors ALS disease progression, where a higher score reflects a better outcome.
Time Frame
24 months
Title
Number of participants with abnormal Slow Vital Capacity measured by hand spirometry at 3 monthly intervals
Description
Slow vital capacity is measured in litres, and as a % of predicted.
Time Frame
24 months
Title
Measure plasma creatinine at 3 monthly intervals
Description
Plasma creatinine is assessed to monitor kidney function
Time Frame
24 months
Title
Assign a value using the King's Staging Scale to describe degree of disease advancement over time
Description
The King's Staging Scale is a clinical staging system defining four stages of ALS assessed by way of a semi-structured interview with the participant.
Time Frame
24 months
Title
Evaluate the incidence of treatment-emergent adverse events
Description
based on physical examinations and patient reported symptoms.
Time Frame
24 months
Title
Measure study medication discontinuation
Description
the number of participants who discontinue study medication will be assessed to assess tolerability
Time Frame
24 months
Title
Measure the score obtained with the Edinburgh Cognitive and Behavioural Assessment Screen (ECAS)
Description
ECAS is a multidomain assessment questionnaire used in ALS to assess cognitive and behavioural changes where a higher score relates to a better outcome.
Time Frame
24 months
Title
Measure the responses in the EQ-5D-5L quality of life health questionnaire.
Description
The EQ-5D-5L questionnaire is a standardised measure of health-related Quality of Life, also incorporating a Visual Analogue Scale. A higher score relates to a better outcome.
Time Frame
24 months
Title
Measurement of several biomarkers from blood and urine samples
Description
Urinary P75ECD, plasma neurofilament light and heavy chain, HERV-K expression and genotyping (UNC13a / C9orf72) will be measured for post-trial exploratory analyses.
Time Frame
24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥ 18 years at the time of screening
Diagnosis of ALS according to the Gold Coast Criteria
Capable of providing informed consent and complying with trial procedures
TRICALS risk profile > -6.0 and < -2.0
Those taking Riluzole must be on a stable dose for at least 30 days prior to the baseline visit or must have stopped taking Riluzole at least 30 days prior to the baseline visit
Women must not become pregnant (e.g., post-menopausal, surgically sterile, using highly effective birth control methods or not having potentially reproductive sex) for the duration of the study. Highly effective methods of birth control are those with a failure rate of < 1% per year when employed consistently and correctly, e.g. Combined (oestrogen and progestogen containing) hormonal contraception or progestogen-only hormonal contraception
Women of childbearing potential must have a negative serum pregnancy test at screening and baseline and be non-lactating. Women of childbearing potential are defined as females who have experienced menarche and are not surgically sterilised (e.g. hysterectomy or bilateral salpingectomy) or post-menopausal (defined as at least 1 year since last regular menstrual period).
For participants taking antacids (regularly or as required), participant is willing and able to avoid taking antacids for at least 2 hours before and 6 hours after Triumeq
Exclusion Criteria:
People who are HLA-B*5701 positive
Known hypersensitivity to Dolutegravir, Abacavir or Lamivudine, or to any of the excipients
Safety Laboratory Criteria at screening:
ALT ≥ 5 times upper limit of normal (ULN)
AST ≥ 3 times ULN
Bilirubin ≥ 1.5 times ULN
Creatinine clearance < 30 mL / min
Platelet concentration of < 100 x109 per L
Absolute neutrophil count of < 1x109 per L
Haemoglobin < 100 g/L
Amylase & lipase ≥ 2 times ULN
Lactate ≥ 2 times ULN
Moderate to severe hepatic impairment, as defined by local clinical guidelines
Presence of HIV antibodies at screening
Presence of Hepatitis C antibodies at screening unless participants have had effective treatment for Hepatitis C
Presence of Hepatitis B core or surface antigen at screening
Participation in any other investigational drug trial or using investigational drug within 30 days prior to screening
Use of NIV ≥22 h per day or having a tracheostomy
Edaravone dose within 30 days prior to screening. Edaravone is approved by the FDA and in Japan, but remains an investigational product in Europe and Australia
Clinically significant history of unstable or severe cardiac, oncological, psychiatric, hepatic, or renal disease or other medically significant illness
Taking medication contraindicated with Triumeq: Dofetilideor Fampridine (dalfampridine)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ammar Al-Chalabi, PhD, FRCP
Phone
+44 20 7848 5174
Email
ammar.al-chalabi@kcl.ac.uk
First Name & Middle Initial & Last Name or Official Title & Degree
Julian Gold, MD, FFPHM
Phone
+61 411 110451
Email
julian.gold@health.nsw.gov.au
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Julian Gold, MD, FFPHM
Organizational Affiliation
Macquarie University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The University of Sydney - Brain and Mind Centre
City
Camperdown
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Matthew Kiernan
Phone
+61291144250
Email
matthew.kiernan@sydney.edu.au
First Name & Middle Initial & Last Name & Degree
Matthew Kiernan, DSc, MBBS, FRACP
Facility Name
MQ Health Neurology
City
North Ryde
State/Province
New South Wales
ZIP/Postal Code
2109
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dominic B Rowe, MBBS, FRACP
Phone
+61298123720
Email
dominic.rowe@mq.edu.au
First Name & Middle Initial & Last Name & Degree
Dominic B Rowe, MBBS, FRACP
Facility Name
Sunshine Coast University Hospital
City
Birtinya
State/Province
Queensland
ZIP/Postal Code
4575
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Antony Winkel, MBBS, PhD
Phone
0752020000
Email
Antony.Winkel@health.qld.gov.au
Facility Name
Royal Brisbane and Women's Hospital
City
Herston
State/Province
Queensland
ZIP/Postal Code
4029
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Robert Henderson
Phone
+61736468111
Email
Robert.Henderson@health.qld.gov.au
First Name & Middle Initial & Last Name & Degree
Robert Henderson, MBBS, PhD, FRACP
Facility Name
Flinders Medical Centre
City
Bedford Park
State/Province
South Australia
ZIP/Postal Code
5042
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Schultz
Phone
+61882044187
Email
david.schultz@sa.gov.au
First Name & Middle Initial & Last Name & Degree
David Schultz, MBBS, FRACP
Facility Name
Launceston General Hospital
City
Launceston
State/Province
Tasmania
ZIP/Postal Code
7250
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lauren Giles
Phone
+61367776001
Email
lauren.giles@ths.tas.gov.au
First Name & Middle Initial & Last Name & Degree
Lauren Giles, MBBS, FRACP
Facility Name
Calvary Health Care Bethlehem
City
Parkdale
State/Province
Victoria
ZIP/Postal Code
3195
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sarah Lee
Phone
+61395962853
Email
ChiuMunSarah.Lee@calvarycare.org.au
First Name & Middle Initial & Last Name & Degree
Sarah Lee, MBBS, FRACP
Facility Name
The Perron Institute
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Merrilee Needham
Phone
+61864570209
Email
Merrilee.Needham@health.wa.gov.au
First Name & Middle Initial & Last Name & Degree
Merrilee Needham, MBBS, PhD, FRACP
Facility Name
Christchurch Hospital
City
Christchurch
ZIP/Postal Code
8011
Country
New Zealand
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Deborah Mason, MBChB, FRACP
Phone
+64-3-3640640
Email
deborah.mason@cdhb.health.nz
Facility Name
Clinical Trials Unit, Tauranga Hospital
City
Tauranga
ZIP/Postal Code
3112
Country
New Zealand
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
James Cleland, MBChB, FRACP
Phone
+64-7-5798000
Email
james.cleland@bopdhb.govt.nz
Facility Name
Wellington Regional Hospital
City
Wellington
ZIP/Postal Code
6021
Country
New Zealand
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Purwa Joshi, MBChB, FRACP
Phone
+64-4-9185136
Email
purwa.joshi@ccdhb.org.nz
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
It is anticipated participant level data will be available as open access.
IPD Sharing Time Frame
Contact the Chief Investigators for access information.
IPD Sharing Access Criteria
Contact the Chief Investigators for access information.
Citations:
PubMed Identifier
31284774
Citation
Gold J, Rowe DB, Kiernan MC, Vucic S, Mathers S, van Eijk RPA, Nath A, Garcia Montojo M, Norato G, Santamaria UA, Rogers ML, Malaspina A, Lombardi V, Mehta PR, Westeneng HJ, van den Berg LH, Al-Chalabi A. Safety and tolerability of Triumeq in amyotrophic lateral sclerosis: the Lighthouse trial. Amyotroph Lateral Scler Frontotemporal Degener. 2019 Nov;20(7-8):595-604. doi: 10.1080/21678421.2019.1632899. Epub 2019 Jul 8.
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