Triumeq in Amyotrophic Lateral Sclerosis (LIGHTHOUSE II)

Randomised Double-Blind Placebo-Controlled Phase 3 Trial of Triumeq in Amyotrophic Lateral Sclerosis

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

Study Overview

• Status: Terminated
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: Placebo; Drug: Dolutegravir, Abacavir and Lamivudine

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.

• Study Type: Interventional
• Enrollment (Actual): 419
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • North Ryde, New South Wales, Australia, 2109
      • MQ Health Neurology
    • Randwick, New South Wales, Australia, 2031
      • Neuroscience Research Australia (NeuRA)
  • Queensland
    • Birtinya, Queensland, Australia, 4575
      • Sunshine Coast University Hospital
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane and Women's Hospital
  • South Australia
    • Bedford Park, South Australia, Australia, 5042
      • Flinders Medical Centre
  • Tasmania
    • Launceston, Tasmania, Australia, 7250
      • Launceston General Hospital
  • Victoria
    • Caulfield South, Victoria, Australia, 3162
      • Calvary Health Care Bethlehem
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • The Perron Institute
• Ireland
  • Dublin, Ireland, D09V2N0
    • Beaumont Hospital
• Netherlands
  • Utrecht, Netherlands, 3584 CX
    • UMC Utrecht
• New Zealand
  • Christchurch, New Zealand, 8011
    • Christchurch Hospital
  • Dunedin, New Zealand, 9054
    • Dunedin Hospital
  • Tauranga, New Zealand, 3112
    • Clinical Trials Unit, Tauranga Hospital
  • Wellington, New Zealand, 6021
    • Wellington Regional Hospital
• Slovenia
  • Ljubljana, Slovenia, 1000
    • Univerzitetni klinicni center Ljubljana
• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • València, Spain, 46026
    • Hospital Universitario y Politécnico La Fe
• Sweden
  • Stockholm, Sweden, 113 61
    • Studiecenheten at Akademiskt specialistcentrum
• United Kingdom
  • Edinburgh, United Kingdom, EH16 4SB
    • University of Edinburgh, Anne Rowling Regenerative Nuerology Clinic
  • Liverpool, United Kingdom, L9 7LJ
    • The Walton Centre
  • London, United Kingdom, SE5 9RS
    • King's College Hospital
  • London, United Kingdom, SW17 0QT
    • St George's Hospital
  • London, United Kingdom, NW1 2PG
    • University College London Hospital
  • Oxford, United Kingdom, OX3 9DU
    • Oxford University Hospital
  • Plymouth, United Kingdom, PL8 8DH
    • Plymouth University Hospital
  • Preston, United Kingdom, PR2 9HT
    • Royal Preston Hospital
  • Sheffield, United Kingdom, S5 7AU
    • Sheffield Teaching Hospital
  • Stoke, United Kingdom, ST4 6QG
    • Royal Stoke Hotel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dolutegravir/Abacavir/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	Drug: Dolutegravir, Abacavir and Lamivudine; Dolutegravir 50mg, Abacavir 600mg and Lamivudine 300mg.; Other Names: Triumeq
Placebo Comparator: Placebo; 4 capsules to be taken orally once daily (all 4 at the same time). Maximum duration is 24months	Drug: Placebo; Matching placebo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure overall survival at 24 months or after a minimum of 212 events	Overall survival is measured as death from any cause, in participants with ALS at 24 months, or after a minimum of 212 events.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure scoring in the ALS-Functional Rating Scale Revised (ALSFRS-R) at 3 monthly intervals.	The ALSFRS-R is a 12 item participant self-report measure that monitors ALS disease progression, where a higher score reflects a better outcome.	24 months
Number of participants with abnormal Slow Vital Capacity measured by hand spirometry at 3 monthly intervals	Slow vital capacity is measured in litres, and as a % of predicted.	24 months
Measure plasma creatinine at 3 monthly intervals	Plasma creatinine is assessed to monitor kidney function	24 months
Assign a value using the King's Staging Scale to describe degree of disease advancement over time	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.	24 months
Evaluate the incidence of treatment-emergent adverse events	based on physical examinations and patient reported symptoms.	24 months
Measure study medication discontinuation	the number of participants who discontinue study medication will be assessed to assess tolerability	24 months
Measure the score obtained with the Edinburgh Cognitive and Behavioural Assessment Screen (ECAS)	ECAS is a multidomain assessment questionnaire used in ALS to assess cognitive and behavioural changes where a higher score relates to a better outcome.	24 months
Measure the responses in the EQ-5D-5L quality of life health questionnaire.	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.	24 months
Measurement of several biomarkers from blood and urine samples	Urinary P75ECD, plasma neurofilament light and heavy chain, HERV-K expression and genotyping (UNC13a / C9orf72) will be measured for post-trial exploratory analyses.	24 months

Collaborators and Investigators

• Sponsor: Macquarie University, Australia
• Collaborators: King's College London; Stichting TRICALS Foundation
• Investigators: Principal Investigator: Julian Gold, MD, FFPHM, Macquarie University

Publications and helpful links

General Publications

• Gold J, Rowe DB, Kiernan MC, Vucic S, Mathers S, van Eijk RPA, Nath A, Garcia Montojo M, Norato G, Santamaria UA, Rogers ML, Malaspina A, Lombardi V, Mehta PR, Westeneng HJ, van den Berg LH, Al-Chalabi A. Safety and tolerability of Triumeq in amyotrophic lateral sclerosis: the Lighthouse trial. Amyotroph Lateral Scler Frontotemporal Degener. 2019 Nov;20(7-8):595-604. doi: 10.1080/21678421.2019.1632899. Epub 2019 Jul 8.

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2022
• Primary Completion (Actual): June 30, 2025
• Study Completion (Actual): June 30, 2025

Study Registration Dates

• First Submitted: December 6, 2021
• First Submitted That Met QC Criteria: January 3, 2022
• First Posted (Actual): January 18, 2022

Study Record Updates

• Last Update Posted (Actual): July 11, 2025
• Last Update Submitted That Met QC Criteria: July 8, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: ALS
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Neuromuscular Diseases; Metabolic Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Nucleic Acid Synthesis Inhibitors; Antiviral Agents; Reverse Transcriptase Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Dolutegravir; Lamivudine; Abacavir
• Other Study ID Numbers: LIGHTHOUSE II; 2020-005069-15 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: It is anticipated participant level data will be available as open access.
• IPD Sharing Time Frame: Contact the Chief Investigators for access information.
• IPD Sharing Access Criteria: Contact the Chief Investigators for access information.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No