To determine if Triumeq improves survival in Amyotrophic Lateral Sclerosis (ALS) compared with placebo
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.
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/CTF
G/2014_09_HMA_CTFG_Contraception.pdf?fbclid=IwAR3AY5Ha0ESDyqIBeUaYI9VTFWmx9bbt8NZ-80
N-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/CT
FG/2014_09_HMA_CTFG_Contraception.pdf?fbclid=IwAR3AY5Ha0ESDyqIBeUaYI9VTFWmx9bbt8NZ-8
0N-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.