Triumeq in Amyotrophic Lateral Sclerosis

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

Detailed Description
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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.

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

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Drug: Dolutegravir, Abacavir and Lamivudine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years at the time of screening Diagnosis of ALS according to the Gold Coast Criteria Capable of providing informed consent and complying with trial procedures TRICALS risk profile > -6.0 and < -2.0 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 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. 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 Women of childbearing potential must have a negative serum pregnancy test at screening and baseline and be non-lactating. Women of childbearing potential are defined as females who have experienced menarche and are not surgically sterilised (e.g. hysterectomy or bilateral salpingectomy) or post-menopausal (defined as at least 1 year since last regular menstrual period). For participants taking antacids (regularly or as required), participant is willing and able to avoid taking antacids for at least 2 hours before and 6 hours after Triumeq Exclusion Criteria: People who are HLA-B*5701 positive Known hypersensitivity to Dolutegravir, Abacavir or Lamivudine, or to any of the excipients Safety Laboratory Criteria at screening: ALT ≥ 5 times upper limit of normal (ULN) AST ≥ 3 times ULN Bilirubin ≥ 1.5 times ULN Creatinine clearance < 30 mL / min Platelet concentration of < 100 x109 per L Absolute neutrophil count of < 1x109 per L Haemoglobin < 100 g/L Amylase & lipase ≥ 2 times ULN Lactate ≥ 2 times ULN Moderate to severe hepatic impairment, as defined by local clinical guidelines Presence of HIV antibodies at screening Presence of Hepatitis C antibodies at screening unless participants have had effective treatment for Hepatitis C Presence of Hepatitis B core or surface antigen at screening Participation in any other investigational drug trial or using investigational drug within 30 days prior to screening Use of NIV ≥22 h per day or having a tracheostomy 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 Clinically significant history of unstable or severe cardiac, oncological, psychiatric, hepatic, or renal disease or other medically significant illness Taking medication contraindicated with Triumeq: Dofetilideor Fampridine (dalfampridine)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomised in a 2:1 ratio to receive either triumeq or placebo
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ALS