Triumeq in Amyotrophic Lateral Sclerosis
- Conditions
- Amyotrophic Lateral Sclerosis
- Interventions
- Drug: Placebo
- Registration Number
- NCT05193994
- Lead Sponsor
- Macquarie University, Australia
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 390
- 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 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
- 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)
- 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
- Participant taking taurursodiol supplements (TUDCA) can participate in this trial if the supplement does not contain sodium phenylbutyrate.
- Participants taking taurursodiol supplements (TUDCA) that also contain sodium phenylbutyrate must be willing to stop supplementation 30 days prior randomisation.
-
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 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
-
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
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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
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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
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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)
-
Taking Tofersen within 3 months prior to screening.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dolutegravir/Abacavir/Lamivudine Dolutegravir, Abacavir and 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 Placebo 4 capsules to be taken orally once daily (all 4 at the same time). Maximum duration is 24months
- Primary Outcome Measures
Name Time Method Measure overall survival at 24 months or after a minimum of 212 events 24 months 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
Name Time Method Measure scoring in the ALS-Functional Rating Scale Revised (ALSFRS-R) at 3 monthly intervals. 24 months The ALSFRS-R is a 12 item participant self-report measure that monitors ALS disease progression, where a higher score reflects a better outcome.
Measure study medication discontinuation 24 months the number of participants who discontinue study medication will be assessed to assess tolerability
Assign a value using the King's Staging Scale to describe degree of disease advancement over time 24 months 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.
Number of participants with abnormal Slow Vital Capacity measured by hand spirometry at 3 monthly intervals 24 months Slow vital capacity is measured in litres, and as a % of predicted.
Measure plasma creatinine at 3 monthly intervals 24 months Plasma creatinine is assessed to monitor kidney function
Evaluate the incidence of treatment-emergent adverse events 24 months based on physical examinations and patient reported symptoms.
Measure the score obtained with the Edinburgh Cognitive and Behavioural Assessment Screen (ECAS) 24 months 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. 24 months 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 24 months Urinary P75ECD, plasma neurofilament light and heavy chain, HERV-K expression and genotyping (UNC13a / C9orf72) will be measured for post-trial exploratory analyses.
Trial Locations
- Locations (28)
Neuroscience Research Australia (NeuRA)
🇦🇺Randwick, New South Wales, Australia
Dunedin Hospital
🇳🇿Dunedin, New Zealand
MQ Health Neurology
🇦🇺North Ryde, New South Wales, Australia
Sunshine Coast University Hospital
🇦🇺Birtinya, Queensland, Australia
Royal Brisbane and Women's Hospital
🇦🇺Herston, Queensland, Australia
Flinders Medical Centre
🇦🇺Bedford Park, South Australia, Australia
Launceston General Hospital
🇦🇺Launceston, Tasmania, Australia
Calvary Health Care Bethlehem
🇦🇺Caulfield South, Victoria, Australia
The Perron Institute
🇦🇺Nedlands, Western Australia, Australia
Beaumont Hospital
🇮🇪Dublin, Ireland
UMC Utrecht
🇳🇱Utrecht, Netherlands
Christchurch Hospital
🇳🇿Christchurch, New Zealand
Clinical Trials Unit, Tauranga Hospital
🇳🇿Tauranga, New Zealand
Wellington Regional Hospital
🇳🇿Wellington, New Zealand
Univerzitetni klinični center Ljubljana
🇸🇮Ljubljana, Slovenia
Hospital del Mar
🇪🇸Barcelona, Spain
Hospital Universitario y Politecnico la Fe
🇪🇸València, Spain
Studiecenheten at Akademiskt specialistcentrum
🇸🇪Stockholm, Sweden
University of Edinburgh, Anne Rowling Regenerative Nuerology Clinic
🇬🇧Edinburgh, United Kingdom
The Walton Centre
🇬🇧Liverpool, United Kingdom
University College London Hospital
🇬🇧London, United Kingdom
King's College Hospital
🇬🇧London, United Kingdom
St George's Hospital
🇬🇧London, United Kingdom
Oxford University Hospital
🇬🇧Oxford, United Kingdom
Plymouth University Hospital
🇬🇧Plymouth, United Kingdom
Royal Preston Hospital
🇬🇧Preston, United Kingdom
Sheffield Teaching Hospital
🇬🇧Sheffield, United Kingdom
Royal Stoke Hotel
🇬🇧Stoke, United Kingdom