Triumeq in Amyotrophic Lateral Sclerosis (LIGHTHOUSE II)

Macquarie University

Status and phase: Terminated; Phase 3

Conditions: Amyotrophic Lateral Sclerosis

Treatments: Drug: Dolutegravir, Abacavir and Lamivudine; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT05193994

2020-005069-15 (EudraCT Number)

LIGHTHOUSE II

Details and patient eligibility

About

To determine if Triumeq improves survival in Amyotrophic Lateral Sclerosis (ALS) compared with placebo

Full 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.

Enrollment: 419 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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419 participants in 2 patient groups, including a placebo group

Dolutegravir/Abacavir/Lamivudine

Experimental group

Description:

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

Treatment:

Drug: Dolutegravir, Abacavir and Lamivudine

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo