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Safety and Tolerability of Antiretroviral (Triumeq) in Patients With Amyotrophic Lateral Sclerosis (ALS). (Lighthouse)

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02868580
First Posted: August 16, 2016
Last Update Posted: July 18, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
Macquarie University, Australia
Westmead Hosptial
Calvary Health Care Bethlehem
The University of Sydney - Brain and Mind Centre
Information provided by (Responsible Party):
Neuroscience Trials Australia
  Purpose
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.

Condition Intervention Phase
Amyotrophic Lateral Sclerosis Drug: Triumeq Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Intervention Model Description:
Safety and Tolerability open label
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 2a Open Label Study, Safety and Tolerability of Combination Antiretroviral Therapy (Triumeq) in Participants With Amyotrophic Lateral Sclerosis (ALS) - The Lighthouse Project.

Resource links provided by NLM:


Further study details as provided by Neuroscience Trials Australia:

Primary Outcome Measures:
  • Number of participants with treatment related adverse events as defined CTCAE V4.0. [ Time Frame: 1 year ]
    Safety will be measured by Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment.


Secondary Outcome Measures:
  • ALS Functional Rating Scale-Revised (ALSFRS-R) scoring [ Time Frame: 1 year ]
    Efficacy will be measured by the change in scores of the ALS Functional Rating Scale-Revised (ALSFRS-R) conducted at screening, twice within the lead-in phase and at four weekly intervals during the study until end of treatment or early termination.

  • Number of Participants With Abnormal Laboratory Values for Neurophysiological Index (NI) Related to Treatment. [ Time Frame: 1 year ]
    A neurophysiological index (NI) measurement will be calculated according to the parameters of Compound Muscle Action Potential amplitude/DML x Frequency % to determine the index score.

  • Number of participants with abnormal Sniff Nasal Inspiratory Pressure (SNIP) Test results [ Time Frame: one year ]
    The SNIP test results will be calculated according to the Pn(sn) as a percentage of predicted value according to treatment.

  • Number of participants with abnormal forced vital capacity (FVC) test results as measured by hand-held spirometry [ Time Frame: One year ]
    The FVC test results will be measured in liters and reported according to percentage of predicted values for participants on treatment

  • Number of participants with abnormal quantitative hand muscle testing as measured by dynanometry. [ Time Frame: One year ]
    The quantitative hand muscle strength will be assessed by 3 Measurements on Grip Strength and Pinch Grip: measurement in kilograms

  • Number of participants with abnormal scores on the Columbia Suicide Severity Score C-SSRS). [ Time Frame: One year ]
    The C-SSRS is a measure of suicidal ideation and behavior. It is a composite numerical scale divided into sections and used to assess selected parameters over time in participants on treatment. The scoring system is both binomial and rating scale and is reported according to different aspects of the assessment.


Other Outcome Measures:
  • Number of participants with abnormal ECG results [ Time Frame: one year ]
    ECGs will be performed at screening, 16 and 24 weeks and early termination for participants on treatment.


Enrollment: 40
Actual Study Start Date: October 2016
Estimated Study Completion Date: June 2018
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single arm open label
All subjects will receive open label Triumeq following a lead-in phase. Triumeq is abacavir 600mg, lamivudine 300mg, dolutegravir 50mg
Drug: Triumeq
Triumeq, a combination of dolutegravir, abacavir and lamivudine is an anti-retroviral therapy indicated for people with HIV-1 infection.
Other Names:
  • dolutegravir (50mg)
  • abacavir (600mg)
  • lamivudine (300mg)

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Subjects must meet all of the following inclusion criteria to be eligible to participate in this study:

  • Age 18-75 years at the time of the screening visit
  • Able to provide informed consent and comply with study procedures
  • Sporadic ALS diagnosed as probable, laboratory-supported probable or definite according to the World Federation of Neurology El Escorial revised criteria as determined by a neurologist with neuromuscular sub-specialty training
  • Diagnosis <24 months from date of enrolment
  • (Forced) Vital capacity at least 60% of predicted value for gender, height and age at the screening visit
  • Must be on a stable dose of riluzole for at least 30 days prior to the screening visit.
  • Subject has established care with a neurologist at one of the four specialized ALS clinics involved in the study and will maintain this clinical care throughout the study.
  • Subjects can participate in clinical registries, but will be excluded to this protocol if they are participating in a clinical trial involving additional or investigative treatment exposure.

Exclusion Criteria:

A participant will be excluded if he or she has any of the following:

  • Dependence on mechanical ventilation at the time of screening
  • Gastrostomy at the time of screening
  • Absence of Upper Motor Neuron Signs
  • Participation in any other investigational drug trial or using investigational drug (within 12 weeks prior to screening)
  • Known hypersensitivity to dolutegravir, abacavir or lamivudine, or to any of the excipients
  • Presence of the HLA-B*5701 allele at screening
  • Presence of a monogenic cause of ALS (e.g. known mutation in SOD1, expansion in c9orf72 etc.)
  • History of positive test or positive result at screening for HIV
  • Subjects positive for Hepatitis B at screening (+HBsAg), or anticipated need for Hepatitis C virus (HCV) therapy during the study*;
  • Women must not be able to become pregnant (post menopausal for >1 year, surgically sterile, adequate contraception) or breastfeed for the duration of the study. Women of childbearing potential must have a negative pregnancy test at screening and be non-lactating
  • Other interventional clinical trial
  • Subject is taking medication contraindicated with Triumeq. Dofetilide (or pilsicainide [available in Japan]) is prohibited as DTG may inhibit its renal tubular secretion resulting in increased dofetilide concentrations and potential for toxicity.
  • Presence of any of the following clinical conditions at the time of screening:

Drug or alcohol abuse Unstable medical disease (such as unstable angina or chronic obstructive pulmonary disease), or active infectious disease (such as Hepatitis B or C or tuberculosis), or current malignancy Unstable psychiatric illness defined as psychosis or untreated major depression within 90 days of the screening visit. This exclusion criteria is based on a prior psychiatric diagnosis that is unstable as determined by the subject's treating Psychiatrist Dementia as previously diagnosed by a medical practitioner

• Safety Laboratory Criteria at the screening visit: Alanine aminotransferase (ALT) >5 times the upper limit of normal (ULN), OR ALT >3xULN Total bilirubin, lactate, triglycerides, amylase, or lipase greater than 2.0 times the upper limit of normal Subject has creatinine clearance of <50 mL/min via Cockroft-Gault method Subjects with moderate to severe hepatic impairment (Class B or greater) as determined by Child-Pugh classification; Absolute neutrophil count of < 1 x 109/L Platelet concentration of < 100 x 109/L Haemoglobin < 100g/L

  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02868580


Locations
Australia, New South Wales
Macquarie Neurology
North Ryde, New South Wales, Australia, 2109
Westmead Hospital
Parramatta, New South Wales, Australia, 2150
Brain and Mind Centre
Sydney, New South Wales, Australia, 2050
Australia, Victoria
Calvary Health Care Bethlehem
Caulfield South, Victoria, Australia, 3162
Sponsors and Collaborators
Neuroscience Trials Australia
Macquarie University, Australia
Westmead Hosptial
Calvary Health Care Bethlehem
The University of Sydney - Brain and Mind Centre
Investigators
Principal Investigator: Julian Gold, MD The Albion Centre
  More Information

Responsible Party: Neuroscience Trials Australia
ClinicalTrials.gov Identifier: NCT02868580     History of Changes
Other Study ID Numbers: CUR-101
First Submitted: June 16, 2016
First Posted: August 16, 2016
Last Update Posted: July 18, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Neuroscience Trials Australia:
ALS
Antiretroviral Therapy, Triumeq

Additional relevant MeSH terms:
Sclerosis
Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases
Lamivudine
Abacavir
Dolutegravir
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Anti-HIV Agents
HIV Integrase Inhibitors
Integrase Inhibitors