Amyotrophic Lateral SclerosisPhase 2LighthouseNCT02868580
Safety and Tolerability of Antiretroviral (Triumeq) in Patients With Amyotrophic Lateral Sclerosis (ALS).
A Phase 2 study testing Triumeq in people with Amyotrophic Lateral Sclerosis, run by Neuroscience Trials Australia at 4 sites in Australia.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- Triumeq
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 4 sitesAustralia
- Study dates
- Oct 2016to Dec 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
Show all 16Show fewer
- 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
Trial locations and contacts
4 sites in 1 country.
Australia4 sites
Calvary Health Care Bethlehem
Caulfield South, Victoria, 3162
Macquarie Neurology
North Ryde, New South Wales, 2109
Westmead Hospital
Parramatta, New South Wales, 2150
Brain and Mind Centre
Sydney, New South Wales, 2050
About this study
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.
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.
Read the 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.
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- Triumeq
- Keywords
- ALS, Antiretroviral Therapy, Triumeq
- Medical subject headings
- Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TriumeqDrug
Also called dolutegravir (50mg), abacavir (600mg), lamivudine (300mg)
Triumeq, a combination of dolutegravir, abacavir and lamivudine is an anti-retroviral therapy indicated for people with HIV-1 infection.
| Study group | Role | What they receive |
|---|---|---|
| Single arm open label | Experimental | All subjects will receive open label Triumeq following a lead-in phase. Triumeq is abacavir 600mg, lamivudine 300mg, dolutegravir 50mg Receives: Drug: Triumeq |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with treatment related adverse events as defined CTCAE V4.0.
Safety will be measured by Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment.
Measured: 1 year
Secondary outcomes (6)
ALS Functional Rating Scale-Revised (ALSFRS-R) scoring
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.
Measured: 1 year
Number of Participants With Abnormal Laboratory Values for Neurophysiological Index (NI) Related to Treatment.
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.
Measured: 1 year
Number of participants with abnormal Sniff Nasal Inspiratory Pressure (SNIP) Test results
The SNIP test results will be calculated according to the Pn(sn) as a percentage of predicted value according to treatment.
Measured: one year
Number of participants with abnormal forced vital capacity (FVC) test results as measured by hand-held spirometry
The FVC test results will be measured in liters and reported according to percentage of predicted values for participants on treatment
Measured: One year
Number of participants with abnormal quantitative hand muscle testing as measured by dynanometry.
The quantitative hand muscle strength will be assessed by 3 Measurements on Grip Strength and Pinch Grip: measurement in kilograms
Measured: One year
Number of participants with abnormal scores on the Columbia Suicide Severity Score C-SSRS).
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.
Measured: One year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2016 (estimated)
- Study startOct 2016
- Primary completionDec 2017
- Study completionDec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Safety and Tolerability open label
- Masking
- None (open label)
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Neuroscience Trials Australia
- Sponsor type
- University, hospital or other
- Collaborators
- Macquarie University, Australia, Westmead Hospital, Calvary Health Care Bethlehem, University of Sydney
- Responsible party
- Sponsor
- Investigators
- Julian Gold, MD, Principal investigator, The Albion Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02868580
- Sponsor's protocol ID
- CUR-101
- Acronym
- Lighthouse
- Status last verified
- Aug 2019
- First submitted
- 16 Jun 2016
- Last updated
- 22 Aug 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Ramirez P, Zuniga G, Sun W, Beckmann A, Ochoa E, DeVos SL, Hyman B, Chiu G, Roy ER, Cao W, Orr M, Buggia-Prevot V, Ray WJ, Frost B. Pathogenic tau accelerates aging-associated activation of transposable elements in the mouse central nervous system. Prog Neurobiol. 2022 Jan;208:102181. doi: 10.1016/j.pneurobio.2021.102181. Epub 2021 Oct 17.
PubMed 34670118
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT02868580
- Acronym / sponsor ID
- Lighthouse / CUR-101
- Conditions
- Amyotrophic Lateral Sclerosis
- Keywords
- ALS, Antiretroviral Therapy, Triumeq
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Neuroscience Trials AustraliaUniversity, hospital or other
- Collaborators
- Macquarie University, Australia, Westmead Hospital, Calvary Health Care Bethlehem, University of Sydney
- Study start
- Oct 2016 (actual)
- Primary completion
- Dec 2017 (actual)
- Study completion
- Dec 2018 (actual)
- First posted
- 16 Aug 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Safety and Tolerability open label
| Arm | Type | Receives |
|---|---|---|
| Single arm open label | Experimental | Drug: TriumeqAll subjects will receive open label Triumeq following a lead-in phase. Triumeq is abacavir 600mg, lamivudine 300mg, dolutegravir 50mg |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TriumeqAlso: dolutegravir (50mg), abacavir (600mg), lamivudine (300mg)Triumeq, a combination of dolutegravir, abacavir and lamivudine is an anti-retroviral therapy indicated for people with HIV-1 infection. | Drug | Single arm open label |
Primary outcome
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.
6 secondary outcomes
ALS Functional Rating Scale-Revised (ALSFRS-R) scoring
Time frame: 1 year
Number of Participants With Abnormal Laboratory Values for Neurophysiological Index (NI) Related to Treatment.
Time frame: 1 year
Number of participants with abnormal Sniff Nasal Inspiratory Pressure (SNIP) Test results
Time frame: one year
Number of participants with abnormal forced vital capacity (FVC) test results as measured by hand-held spirometry
Time frame: One year
Number of participants with abnormal quantitative hand muscle testing as measured by dynanometry.
Time frame: One year
Number of participants with abnormal scores on the Columbia Suicide Severity Score C-SSRS).
Time frame: One year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2019.
- Derived from this study: PubMed 34670118Ramirez P, Zuniga G, Sun W, Beckmann A, Ochoa E, DeVos SL, Hyman B, Chiu G, Roy ER, Cao W, Orr M, Buggia-Prevot V, Ray WJ, Frost B. Pathogenic tau accelerates aging-associated activation of transposable elements in the mouse central nervous system. Prog Neurobiol. 2022 Jan;208:102181. doi: 10.1016/j.pneurobio.2021.102181. Epub 2021 Oct 17.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Julian Gold, MD principal investigator
The Albion Centre
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Triumeq in people with Amyotrophic Lateral Sclerosis, run by Neuroscience Trials Australia at 4 sites in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with treatment related adverse events as defined CTCAE V4.0. (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02868580, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2019.