Amyotrophic Lateral Sclerosis
Conditions
Keywords
ALS
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.
Interventions
DRUGDolutegravir, Abacavir and Lamivudine
Dolutegravir 50mg, Abacavir 600mg and Lamivudine 300mg.
DRUGPlacebo
Matching placebo.
Sponsors
King's College London
Stichting TRICALS Foundation
Macquarie University, Australia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double-blind
Intervention model description
Participants will be randomised in a 2:1 ratio to receive either triumeq or placebo
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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. |
| Evaluate the incidence of treatment-emergent adverse events | 24 months | based on physical examinations and patient reported symptoms. |
| 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 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. |
| Measure study medication discontinuation | 24 months | the number of participants who discontinue study medication will be assessed to assess tolerability |
Countries
Australia, Ireland, Netherlands, New Zealand, Slovenia, Spain, Sweden, United Kingdom
Outcome results
None listed