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Safety and Tolerability of Triumeq in Amyotrophic Lateral Sclerosis: The Lighthouse Trial

30 Pages Posted: 8 Mar 2019

See all articles by Julian Gold

Julian Gold

The University of Sydney - The Albion Centre

Dominic B Rowe

affiliation not provided to SSRN

Matthew C Kiernan

affiliation not provided to SSRN

Steve Vucic

affiliation not provided to SSRN

Susan Mathers

affiliation not provided to SSRN

Ruben P van Eijk

affiliation not provided to SSRN

Avindra Nath

affiliation not provided to SSRN

Marta Garcia Montojo

affiliation not provided to SSRN

Gina Norato

affiliation not provided to SSRN

Ulisses A Santamaria

affiliation not provided to SSRN

Mary-Louise Rogers

affiliation not provided to SSRN

Andrea Malaspina

affiliation not provided to SSRN

Vittoria Lombardi

affiliation not provided to SSRN

Puja R Mehta

affiliation not provided to SSRN

Henk-Jan Westeneng

affiliation not provided to SSRN

Leonard H van den Berg

affiliation not provided to SSRN

Ammar Al-Chalabi

affiliation not provided to SSRN

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Abstract

Background: Neuroinflammation and human endogenous retroviruses (HERV-K) are thought to have a role in the pathophysiology of amyotrophic lateral sclerosis (ALS). Therapy directed against endogenous retroviruses has demonstrated positive effects during in-vitro and biomarker studies. Consequently, the present study was undertaken to assess the safety and tolerability of long-term Triumeq (abacavir, lamivudine and dolutegravir) exposure in patients with ALS and to assess efficacy against biomarkers of disease progression.

Methods: Patients were observed during a 10-week lead-in period before receiving Triumeq treatment for 24 weeks at four specialist ALS centres. The primary outcomes were safety and tolerability. Secondary outcomes included HERV-K expression levels, urinary p75ECD levels, neurophysiological parameters and clinical outcomes. The ENCALS prediction model was applied to provide an estimate of the cohort survival. The trial was registered on www.clinicaltrials.gov (NCT02868580).

Findings: 40 patients with ALS received Triumeq and 35 (88%) completed treatment. There were no drug-related serious adverse events; one patient was withdrawn from the study due to a drug-associated increase in liver enzymes. A favourable response on HERV-K expression levels was observed, accompanied by a potential slowing in ALSFRS-R progression rate of 21.8% (95% CI -4.8 %- 48.6%) and the amount of urinary p75ECD measured. One patient died five months after stopping treatment, while five were expected to have died during the treatment period (interquartile range 2-8).

Interpretation: Long-term Triumeq exposure was safe and well tolerated. There was suggestive evidence for a biological response in pharmacodynamic and clinical biomarkers. A larger international phase III trial will be deployed to assess the effect of Triumeq on overall survival and disease progression.

Funding: Funding was provided by the FightMND Foundation; MND Research Institute of Australia; MND Association, United Kingdom. ViiV Healthcare provided the Triumeq.

Declaration of Interest: The authors have no conflict of interest with respect to the research or data presented in this study. No funder was involved in the study design or interpretation or reporting of the results.

Ethical Approval: The relevant ethics committees at each site approved the protocol. The study was conducted in accordance with Good Clinical Practice (GCP) and the Declaration of Helsinki (2000). The trial was registered on clinicaltrials.gov (NCT02868580).

Suggested Citation

Gold, Julian and Rowe, Dominic B and Kiernan, Matthew C and Vucic, Steve and Mathers, Susan and van Eijk, Ruben P and Nath, Avindra and Garcia Montojo, Marta and Norato, Gina and Santamaria, Ulisses A and Rogers, Mary-Louise and Malaspina, Andrea and Lombardi, Vittoria and Mehta, Puja R and Westeneng, Henk-Jan and van den Berg, Leonard H and Al-Chalabi, Ammar, Safety and Tolerability of Triumeq in Amyotrophic Lateral Sclerosis: The Lighthouse Trial (March 6, 2019). Available at SSRN: https://ssrn.com/abstract=3347916 or http://dx.doi.org/10.2139/ssrn.3347916

Julian Gold (Contact Author)

The University of Sydney - The Albion Centre ( email )

150 Albion Street
Surry Hills, NSW 2010
Australia

Dominic B Rowe

affiliation not provided to SSRN

Matthew C Kiernan

affiliation not provided to SSRN

Steve Vucic

affiliation not provided to SSRN

Susan Mathers

affiliation not provided to SSRN

Ruben P Van Eijk

affiliation not provided to SSRN

Avindra Nath

affiliation not provided to SSRN

Marta Garcia Montojo

affiliation not provided to SSRN

Gina Norato

affiliation not provided to SSRN

Ulisses A Santamaria

affiliation not provided to SSRN

Mary-Louise Rogers

affiliation not provided to SSRN

Andrea Malaspina

affiliation not provided to SSRN

Vittoria Lombardi

affiliation not provided to SSRN

Puja R Mehta

affiliation not provided to SSRN

Henk-Jan Westeneng

affiliation not provided to SSRN

Leonard H Van den Berg

affiliation not provided to SSRN

Ammar Al-Chalabi

affiliation not provided to SSRN

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