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

Launched by NEUROSCIENCE TRIALS AUSTRALIA · Aug 11, 2016

Keywords

ClinConnect Summary

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 a...

Gender

ALL

Eligibility 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