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

NCT02868580 | Completed Phase 2 DMC

• 1 other identifier: CUR-101
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 4

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.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

ALS; Antiretroviral Therapy, Triumeq

Outcome Measures

Primary Outcomes (1)

• 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.

  1 year

Secondary Outcomes (6)

• ALS Functional Rating Scale-Revised (ALSFRS-R) scoring

  1 year

• Number of Participants With Abnormal Laboratory Values for Neurophysiological Index (NI) Related to Treatment.

  1 year

• Number of participants with abnormal Sniff Nasal Inspiratory Pressure (SNIP) Test results

  one year

• Number of participants with abnormal forced vital capacity (FVC) test results as measured by hand-held spirometry

  One year

• Number of participants with abnormal quantitative hand muscle testing as measured by dynanometry.

  One year

Other Outcomes (1)

• Number of participants with abnormal ECG results

  one year

Study Arms (1)

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

Drug: Triumeq

Interventions

Triumeq DRUG

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

Also known as: dolutegravir (50mg), abacavir (600mg), lamivudine (300mg)

Single arm open label

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• 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

Sponsors & Collaborators

• Neuroscience Trials Australia: lead
• Macquarie University, Australia: collaborator
• Westmead Hosptial: collaborator
• Calvary Health Care Bethlehem: collaborator
• The University of Sydney - Brain and Mind Centre: collaborator

Study Sites (4)

Macquarie Neurology

North Ryde, New South Wales, 2109, Australia

Location

Westmead Hospital

Parramatta, New South Wales, 2150, Australia

Location

Brain and Mind Centre

Sydney, New South Wales, 2050, Australia

Location

Calvary Health Care Bethlehem

Caulfield South, Victoria, 3162, Australia

Location

Related Publications (1)

• 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.

  PMID: 34670118 DERIVED

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

abacavir, dolutegravir, and lamivudine drug combination; dolutegravir; abacavir; Lamivudine

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides

Study Officials

• Julian Gold, MD

  The Albion Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Safety and Tolerability open label

Study Record Dates

• First Submitted: June 16, 2016
• First Posted: August 16, 2016
• Study Start: October 1, 2016
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2018
• Last Updated: August 22, 2019

Record last verified: 2019-08

Locations

AU (4)