Safety and Tolerability of Antiretroviral (Triumeq) in Patients With Amyotrophic Lateral Sclerosis (ALS). (Lighthouse)
|ClinicalTrials.gov Identifier: NCT02868580|
Recruitment Status : Active, not recruiting
First Posted : August 16, 2016
Last Update Posted : March 30, 2018
|Condition or disease||Intervention/treatment||Phase|
|Amyotrophic Lateral Sclerosis||Drug: Triumeq||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Safety and Tolerability open label|
|Masking:||None (Open Label)|
|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.|
|Actual Study Start Date :||October 2016|
|Actual Primary Completion Date :||December 2017|
|Estimated Study Completion Date :||June 2018|
U.S. FDA Resources
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
Triumeq, a combination of dolutegravir, abacavir and lamivudine is an anti-retroviral therapy indicated for people with HIV-1 infection.
- 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.
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02868580
|Australia, New South Wales|
|North Ryde, New South Wales, Australia, 2109|
|Parramatta, New South Wales, Australia, 2150|
|Brain and Mind Centre|
|Sydney, New South Wales, Australia, 2050|
|Calvary Health Care Bethlehem|
|Caulfield South, Victoria, Australia, 3162|
|Principal Investigator:||Julian Gold, MD||The Albion Centre|