Safety and Tolerability of Antiretroviral (Triumeq) in Patients With Amyotrophic Lateral Sclerosis (ALS).
Condition: Amyotrophic Lateral Sclerosis
MeSH terms: Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis
Study type: Interventional
Phase: Phase 2

Summary: 
      This is a phase 2a open label, multicentre design study to investigate the safety of Triumeq
      in patients with ALS at 24 weeks post treatment. In this phase 2a study the investigators aim
      to determine whether a combination of anti-retroviral therapy, Triumeq (dolutegravir 50mg,
      abacavir 600mg, lamivudine 300mg) is tolerated and safe in patients with ALS. As secondary
      outcomes, ALSFRS-R, ALSQOL, physical examination, neurophysical parameters and respiratory
      and muscle function will be evaluated. Blood and urine samples will be stored for possible
      future analysis for viral activity. Subjects will be screened for the study after signing an
      approved Informed consent document.
    

Detailed description: 
      This study will be a multi-centre, open-label longitudinal study to investigate the safety
      and tolerability of combination antiretroviral therapy (Triumeq) in Motor Neuron Disease
      (MND)/Amyotrophic Lateral Sclerosis (ALS) for 24 weeks in 40 HIV negative ALS patients.

      The overall study duration will be 34 weeks, with up to 14 days for screening, followed by an
      8-week lead-in phase and 24-week treatment phase. Outcomes will be measured at 4, 8, 12, 20
      and 24 weeks. Participants will be followed at 4-weekly intervals for safety and clinical
      measures.

      Subjects will be screened for the study after signing an approved Informed consent form. As
      part of the 14 day screening phase, subjects will undertake an extensive medical and
      neurological assessments.

      Following the screening phase subjects will enter the 8 week lead-in-phase. During this
      phase, they will undertake two ALSFRS-R at 4 week intervals. The ALSFRS-R will be undertaken
      with the subject by telephone.

      At the baseline visit, following the lead-in-period, blood and urine will be taken for safety
      monitoring and also bio-banked for possible future measurement of Human Endogenous
      Retroviruses (HERVs). Baseline signs and symptoms will be collected.

      All subjects will have their inclusion and exclusion criteria checked at the Baseline visit
      (Week 0) and eligible subjects will start the Triumeq.

      Subjects will return to the centre on Weeks 4, 8, 16, 24 and at 7 days after the last dose of
      investigational product (or early termination) to undertake a neurological examination as
      well as an assessment of the ALS Functional Rating Scale-Revised (ALSFRS-R), neurophysical
      index (NPI), forced vital capacity (FVC) as measured by handheld spirometer, SNIP test and
      quantitative hand muscle testing by dynamometry. All subjects will undertake an evaluation of
      hematological and biochemical parameters and collection of blood and urine samples for
      bio-banking. A voice recording will be undertaken.

      At early termination visit, subjects will undergo an ECG Test. At baseline, weeks 8, 16 and
      24 or early termination visit subjects will be asked to complete the Columbia Suicide
      Severity Rating Scale. At screening week 8 and end of treatment/early termination visit,
      subjects will also be asked to complete an ALSFRS-R.

      SAE's, AE's and changes to concomitant medications will be observed and evaluated throughout
      the study. Each study visit will have a 7 day window after the due date to account for
      scheduling conflicts/holidays/weekends.

      Subjects will be given additional study product to account for the 7- day window.
    

Intervention name(s): Triumeq
Intervention type(s): Drug
Intervention description(s): Triumeq, a combination of dolutegravir, abacavir and lamivudine is an anti-retroviral therapy indicated for people with HIV-1 infection.
Other intervention name(s): dolutegravir (50mg); abacavir (600mg); lamivudine (300mg)
Intervention MeSH terms: Lamivudine; Abacavir; Dolutegravir; Abacavir, dolutegravir, and lamivudine drug combination
Intervention model: Single Group Assignment
Intervention model description: Safety and Tolerability open label
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: ALS; Antiretroviral Therapy, Triumeq