Triumeq in Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis Clinical Trial

— LIGHTHOUSE II  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05193994
• Other study ID #: LIGHTHOUSE II
• Secondary ID: 2020-005069-15
• Status: Recruiting
• Phase: Phase 3
• Start date: February 24, 2022
• Est. completion date: July 1, 2026

Study information

• Verified date: May 2024
• Source: Macquarie University, Australia
• Contact: Ammar Al-Chalabi, PhD, FRCP
• Phone: +44 20 7848 5174
• Email: ammar.al-chalabi[@]kcl.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 390
• Est. completion date: July 1, 2026
• Est. primary completion date: December 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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-5M E6pkBb1UHvFsTwqlQ

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-5 ME6pkBb1UHvFsTwqlQ)

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.

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Drug:
• Dolutegravir, Abacavir and Lamivudine
Dolutegravir 50mg, Abacavir 600mg and Lamivudine 300mg.
• Placebo
Matching placebo.

Locations

Country	Name	City	State
Australia	Flinders Medical Centre	Bedford Park	South Australia
Australia	Sunshine Coast University Hospital	Birtinya	Queensland
Australia	The University of Sydney - Brain and Mind Centre	Camperdown	New South Wales
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	Launceston General Hospital	Launceston	Tasmania
Australia	The Perron Institute	Nedlands	Western Australia
Australia	MQ Health Neurology	North Ryde	New South Wales
Australia	Calvary Health Care Bethlehem	Parkdale	Victoria
Ireland	Beaumont Hospital	Dublin
Netherlands	UMC Utrecht	Utrecht
New Zealand	Christchurch Hospital	Christchurch
New Zealand	Clinical Trials Unit, Tauranga Hospital	Tauranga
New Zealand	Wellington Regional Hospital	Wellington
Slovenia	Univerzitetni klinicni center Ljubljana	Ljubljana
Spain	Hospital del Mar	Barcelona
Spain	Hospital Universitario y Politecnico la Fe	València
Sweden	Studiecenheten at Akademiskt specialistcentrum	Stockholm
United Kingdom	University of Edinburgh, Anne Rowling Regenerative Nuerology Clinic	Edinburgh
United Kingdom	The Walton Centre	Liverpool
United Kingdom	King's College Hospital	London
United Kingdom	St George's Hospital	London
United Kingdom	University College London Hospital	London
United Kingdom	Oxford University Hospital	Oxford
United Kingdom	Plymouth University Hospital	Plymouth
United Kingdom	Royal Preston Hospital	Preston
United Kingdom	Sheffield Teaching Hospital	Sheffield
United Kingdom	Royal Stoke Hotel	Stoke

Sponsors (3)

Lead Sponsor	Collaborator
Macquarie University, Australia	King's College London, Stichting TRICALS Foundation

Countries where clinical trial is conducted

Australia,  Ireland,  Netherlands,  New Zealand,  Slovenia,  Spain,  Sweden,  United Kingdom, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Measure plasma creatinine at 3 monthly intervals	Plasma creatinine is assessed to monitor kidney function	24 months
Secondary	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
Secondary	Evaluate the incidence of treatment-emergent adverse events	based on physical examinations and patient reported symptoms.	24 months
Secondary	Measure study medication discontinuation	the number of participants who discontinue study medication will be assessed to assess tolerability	24 months
Secondary	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
Secondary	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
Secondary	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