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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02868580




Trial ID
NCT02868580
Ethics application status
Date submitted
16/06/2016
Date registered
11/08/2016
Date last updated
28/03/2018

Titles & IDs
Public title
Safety and Tolerability of Antiretroviral (Triumeq) in Patients With Amyotrophic Lateral Sclerosis (ALS).
Scientific title
Phase 2a Open Label Study, Safety and Tolerability of Combination Antiretroviral Therapy (Triumeq) in Participants With Amyotrophic Lateral Sclerosis (ALS) - The Lighthouse Project.
Secondary ID [1] 0 0
CUR-101
Universal Trial Number (UTN)
Trial acronym
Lighthouse
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Amyotrophic Lateral Sclerosis 0 0
Condition category
Condition code
Neurological 0 0 0 0
Neurodegenerative diseases
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Triumeq

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


Treatment: Drugs: Triumeq
Triumeq, a combination of dolutegravir, abacavir and lamivudine is an anti-retroviral therapy indicated for people with HIV-1 infection.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
1 year
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
1 year
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
1 year
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
one year
Secondary outcome [4] 0 0
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
Timepoint [4] 0 0
One year
Secondary outcome [5] 0 0
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
Timepoint [5] 0 0
One year
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
One year

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Macquarie Neurology - North Ryde
Recruitment hospital [2] 0 0
Westmead Hospital - Parramatta
Recruitment hospital [3] 0 0
Brain and Mind Centre - Sydney
Recruitment hospital [4] 0 0
Calvary Health Care Bethlehem - Caulfield South
Recruitment postcode(s) [1] 0 0
2109 - North Ryde
Recruitment postcode(s) [2] 0 0
2150 - Parramatta
Recruitment postcode(s) [3] 0 0
2050 - Sydney
Recruitment postcode(s) [4] 0 0
3162 - Caulfield South

Funding & Sponsors
Primary sponsor type
Other
Name
Neuroscience Trials Australia
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Macquarie University, Australia
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Westmead Hosptial
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Calvary Health Care Bethlehem
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
The University of Sydney - Brain and Mind Centre
Address [4] 0 0
Country [4] 0 0

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/show/NCT02868580
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Julian Gold, MD
Address 0 0
The Albion Centre
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries