Clinical trial NCT05193994: Triumeq in Amyotrophic Lateral Sclerosis
Official title: Randomised Double-Blind Placebo-Controlled Phase 3 Trial of Triumeq in Amyotrophic Lateral Sclerosis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Amyotrophic Lateral Sclerosis
Keywords: ALS
Lead sponsor: Macquarie University, Australia
Sponsor class: OTHER
Collaborators: name: King's College London
name: Stichting TRICALS Foundation
First posted: 2022-01-18
Enrollment: 390
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomised in a 2:1 ratio to receive either triumeq or placebo
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Measure overall survival at 24 months or after a minimum of 212 events
timeFrame: 24 months
Secondary outcomes:
measure: Measure scoring in the ALS-Functional Rating Scale Revised (ALSFRS-R) at 3 monthly intervals.
timeFrame: 24 months
measure: Number of participants with abnormal Slow Vital Capacity measured by hand spirometry at 3 monthly intervals
timeFrame: 24 months
measure: Measure plasma creatinine at 3 monthly intervals
timeFrame: 24 months
measure: Assign a value using the King's Staging Scale to describe degree of disease advancement over time
timeFrame: 24 months
measure: Evaluate the incidence of treatment-emergent adverse events
timeFrame: 24 months
measure: Measure study medication discontinuation
timeFrame: 24 months
measure: Measure the score obtained with the Edinburgh Cognitive and Behavioural Assessment Screen (ECAS)
timeFrame: 24 months
measure: Measure the responses in the EQ-5D-5L quality of life health questionnaire.
timeFrame: 24 months
measure: Measurement of several biomarkers from blood and urine samples
timeFrame: 24 months
Other outcomes:
Locations:
city: North Ryde
country: Australia
facility: MQ Health Neurology
state: New South Wales
city: Randwick
country: Australia
facility: Neuroscience Research Australia (NeuRA)
state: New South Wales
city: Birtinya
country: Australia
facility: Sunshine Coast University Hospital
state: Queensland
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Launceston
country: Australia
facility: Launceston General Hospital
state: Tasmania
city: Caulfield South
country: Australia
facility: Calvary Health Care Bethlehem
state: Victoria
city: Nedlands
country: Australia
facility: The Perron Institute
state: Western Australia
city: Dublin
country: Ireland
facility: Beaumont Hospital
city: Utrecht
country: Netherlands
facility: UMC Utrecht
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Dunedin
country: New Zealand
facility: Dunedin Hospital
city: Tauranga
country: New Zealand
facility: Clinical Trials Unit, Tauranga Hospital
city: Wellington
country: New Zealand
facility: Wellington Regional Hospital
city: Ljubljana
country: Slovenia
facility: Univerzitetni klinični center Ljubljana
city: Barcelona
country: Spain
facility: Hospital del Mar
city: València
country: Spain
facility: Hospital Universitario y Politecnico la Fe
city: Stockholm
country: Sweden
facility: Studiecenheten at Akademiskt specialistcentrum
city: Edinburgh
country: United Kingdom
facility: University of Edinburgh, Anne Rowling Regenerative Nuerology Clinic
city: Liverpool
country: United Kingdom
facility: The Walton Centre
city: London
country: United Kingdom
facility: University College London Hospital
city: London
country: United Kingdom
facility: King's College Hospital
city: London
country: United Kingdom
facility: St George's Hospital
city: Oxford
country: United Kingdom
facility: Oxford University Hospital
city: Plymouth
country: United Kingdom
facility: Plymouth University Hospital
city: Preston
country: United Kingdom
facility: Royal Preston Hospital
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospital
city: Stoke
country: United Kingdom
facility: Royal Stoke Hotel
Study officials:
affiliation: Macquarie University
name: Julian Gold, MD, FFPHM
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.