Randomized double-blind placebo-controlled Phase III trial of Triumeq in amyotrophic lateral sclerosis
Amyotrophic Lateral Sclerosis (ALS)
Lighthouse II is an international, phase III, multi-centre, parallel-group, placebo-controlled, blinded (participant, investigators, analyst) randomised controlled trial of Triumeq (abacavir 600 mg, lamivudine 300 mg and dolutegravir 50 mg) or matched placebo, once daily in addition to standard care, in a 2:1 treatment/placebo allocation ratio in participants with ALS, in order to determine the superiority of treatment versus placebo. If the trial is not terminated at a planned interim analysis, the trial will continue until 24 months after the last enrolled participant or a minimum of 212 events have occurred, whichever is first.
Current inclusion criteria as of 13/02/2024: 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 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 8. For participants taking antacids (regularly or as required), the participant is willing and able to avoid taking antacids for at least 6 hours before and 2 hours after Triumeq 9. Participants 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 to randomisation. Previous inclusion criteria: 1. Age ≥ 18 years at the time of screening 2. Diagnosis of ALS according to the Gold C
Current exclusion criteria as of 13/02/2024: 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: 3.1. ALT ≥ 5 times upper limit of normal (ULN) 3.2. AST ≥ 3 times ULN 3.3. Bilirubin ≥ 1.5 times ULN with clinical indicators of liver disease 3.4. Creatinine clearance < 30 ml/min 3.5. Platelet concentration of < 100 x109 per l 3.6. Absolute neutrophil count of < 1x109 per l 3.7. Haemoglobin < 100 g/l 3.8. Amylase ≥ 2 times ULN 3.9. 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: dofetilide or fampridine (dalfampridine) 13. Taking Tofersen within 3 months prior to screening. Previous 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: 3.1. ALT ≥ 5 times upper limit of normal (ULN) 3.2. AST ≥ 3 times ULN 3.3. Bilirubin ≥ 1.5 times ULN 3.4. Creatinine clearance < 30 ml/min 3.5. Platelet concentration of < 100 x109 per l 3.6. Absolute neutrophil count of < 1x109 per l 3.7. Haemoglobin < 100 g/l 3.