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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05193994




Registration number
NCT05193994
Ethics application status
Date submitted
6/12/2021
Date registered
18/01/2022

Titles & IDs
Public title
Triumeq in Amyotrophic Lateral Sclerosis
Scientific title
Randomised Double-Blind Placebo-Controlled Phase 3 Trial of Triumeq in Amyotrophic Lateral Sclerosis
Secondary ID [1] 0 0
2020-005069-15
Secondary ID [2] 0 0
LIGHTHOUSE II
Universal Trial Number (UTN)
Trial acronym
LIGHTHOUSE II
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Amyotrophic Lateral Sclerosis 0 0
Condition category
Condition code
Neurological 0 0 0 0
Neurodegenerative diseases
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Dolutegravir, Abacavir and Lamivudine
Treatment: Drugs - Placebo

Experimental: Dolutegravir/Abacavir/Lamivudine - 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

Placebo comparator: Placebo - 4 capsules to be taken orally once daily (all 4 at the same time). Maximum duration is 24months


Treatment: Drugs: Dolutegravir, Abacavir and Lamivudine
Dolutegravir 50mg, Abacavir 600mg and Lamivudine 300mg.

Treatment: Drugs: Placebo
Matching placebo.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Measure overall survival at 24 months or after a minimum of 212 events
Timepoint [1] 0 0
24 months
Secondary outcome [1] 0 0
Measure scoring in the ALS-Functional Rating Scale Revised (ALSFRS-R) at 3 monthly intervals.
Timepoint [1] 0 0
24 months
Secondary outcome [2] 0 0
Number of participants with abnormal Slow Vital Capacity measured by hand spirometry at 3 monthly intervals
Timepoint [2] 0 0
24 months
Secondary outcome [3] 0 0
Measure plasma creatinine at 3 monthly intervals
Timepoint [3] 0 0
24 months
Secondary outcome [4] 0 0
Assign a value using the King's Staging Scale to describe degree of disease advancement over time
Timepoint [4] 0 0
24 months
Secondary outcome [5] 0 0
Evaluate the incidence of treatment-emergent adverse events
Timepoint [5] 0 0
24 months
Secondary outcome [6] 0 0
Measure study medication discontinuation
Timepoint [6] 0 0
24 months
Secondary outcome [7] 0 0
Measure the score obtained with the Edinburgh Cognitive and Behavioural Assessment Screen (ECAS)
Timepoint [7] 0 0
24 months
Secondary outcome [8] 0 0
Measure the responses in the EQ-5D-5L quality of life health questionnaire.
Timepoint [8] 0 0
24 months
Secondary outcome [9] 0 0
Measurement of several biomarkers from blood and urine samples
Timepoint [9] 0 0
24 months

Eligibility
Key inclusion criteria
1. Age = 18 years at the time of screening
2. Diagnosis of ALS according to the Gold Coast Criteria
3. Capable of providing informed consent and complying with trial procedures
4. TRICALS risk profile > -6.0 and < -2.0
5. 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
6. 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 plus five days. 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. For more information, please refer to the HMA CTFG Guidelines: https://www.hma.eu/fileadmin/dateien/Human_Medicines/01-About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf?fbclid=IwAR3AY5Ha0ESDyqIBeUaYI9VTFWmx9bbt8NZ-80N-5ME6pkBb1UHvFsTwqlQ
7. Women of childbearing potential must have a negative serum pregnancy test at screening and be non-lactating. Patients will be advised regarding appropriate contraception. A menstruation history will be taken at each visit. Women of childbearing potential are defined as females who are fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy (https://www.hma.eu/fileadmin/dateien/Human_Medicines/01-About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf?fbclid=IwAR3AY5Ha0ESDyqIBeUaYI9VTFWmx9bbt8NZ-80N-5ME6pkBb1UHvFsTwqlQ)
8. For participants taking antacids (regularly or as required), participant is willing and able to avoid taking antacids for at least 6 hours before and 2 hours after Triumeq
9. Participant taking taurursodiol supplements (TUDCA) can participate in this trial if the supplement does not contain sodium phenylbutyrate.
10. Participants taking taurursodiol supplements (TUDCA) that also contain sodium phenylbutyrate must be willing to stop supplementation 30 days prior randomisation.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. People who are HLA-B*5701 positive
2. Known hypersensitivity to Dolutegravir, Abacavir or Lamivudine, or to any of the excipients
3. Safety Laboratory Criteria at screening:

* ALT = 5 times upper limit of normal (ULN)
* AST = 3 times ULN
* Bilirubin = 1.5 times ULN with clinical indicators of liver disease
* Creatinine clearance < 30 mL / min
* Platelet concentration of < 100 x109 per L
* Absolute neutrophil count of < 1x109 per L
* Haemoglobin < 100 g/L
* Amylase = 2 times ULN
* Lactate = 2 times ULN
4. Moderate to severe hepatic impairment, as defined by local clinical guidelines
5. Presence of HIV antibodies at screening
6. Presence of Hepatitis C antibodies at screening unless participants have had effective treatment for Hepatitis C
7. Presence of Hepatitis B core or surface antigen at screening
8. Participation in any other investigational drug trial or using investigational drug within 30 days prior to screening
9. Use of NIV =22 h per day or having a tracheostomy
10. 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
11. Clinically significant history of unstable or severe cardiac, oncological, psychiatric, hepatic, or renal disease or other medically significant illness
12. Taking medication contraindicated with Triumeq: Dofetilideor Fampridine (dalfampridine)
13. Taking Tofersen within 3 months prior to screening.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
24/02/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/07/2026
Actual
Sample size
Target
390
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,VIC,WA
Recruitment hospital [1] 0 0
The University of Sydney - Brain and Mind Centre - Camperdown
Recruitment hospital [2] 0 0
MQ Health Neurology - North Ryde
Recruitment hospital [3] 0 0
Sunshine Coast University Hospital - Birtinya
Recruitment hospital [4] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [5] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [6] 0 0
Launceston General Hospital - Launceston
Recruitment hospital [7] 0 0
Calvary Health Care Bethlehem - Parkdale
Recruitment hospital [8] 0 0
The Perron Institute - Nedlands
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2109 - North Ryde
Recruitment postcode(s) [3] 0 0
4575 - Birtinya
Recruitment postcode(s) [4] 0 0
4029 - Herston
Recruitment postcode(s) [5] 0 0
5042 - Bedford Park
Recruitment postcode(s) [6] 0 0
7250 - Launceston
Recruitment postcode(s) [7] 0 0
3195 - Parkdale
Recruitment postcode(s) [8] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
Ireland
State/province [1] 0 0
Dublin
Country [2] 0 0
Netherlands
State/province [2] 0 0
Utrecht
Country [3] 0 0
New Zealand
State/province [3] 0 0
Christchurch
Country [4] 0 0
New Zealand
State/province [4] 0 0
Tauranga
Country [5] 0 0
New Zealand
State/province [5] 0 0
Wellington
Country [6] 0 0
Slovenia
State/province [6] 0 0
Ljubljana
Country [7] 0 0
Spain
State/province [7] 0 0
Barcelona
Country [8] 0 0
Spain
State/province [8] 0 0
València
Country [9] 0 0
Sweden
State/province [9] 0 0
Stockholm
Country [10] 0 0
United Kingdom
State/province [10] 0 0
Edinburgh
Country [11] 0 0
United Kingdom
State/province [11] 0 0
Liverpool
Country [12] 0 0
United Kingdom
State/province [12] 0 0
London
Country [13] 0 0
United Kingdom
State/province [13] 0 0
Oxford
Country [14] 0 0
United Kingdom
State/province [14] 0 0
Plymouth
Country [15] 0 0
United Kingdom
State/province [15] 0 0
Preston
Country [16] 0 0
United Kingdom
State/province [16] 0 0
Sheffield
Country [17] 0 0
United Kingdom
State/province [17] 0 0
Stoke

Funding & Sponsors
Primary sponsor type
Other
Name
Macquarie University, Australia
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
King's College London
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Stichting TRICALS Foundation
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Julian Gold, MD, FFPHM
Address 0 0
Macquarie University
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Ammar Al-Chalabi, PhD, FRCP
Address 0 0
Country 0 0
Phone 0 0
+44 20 7848 5174
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
It is anticipated participant level data will be available as open access.

Supporting document/s available: Study protocol
When will data be available (start and end dates)?
Contact the Chief Investigators for access information.
Available to whom?
Contact the Chief Investigators for access information.
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05193994