Clinical trial NCT02519036: Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ISIS 443139 in Participants With Early Manifest Huntington's Disease
Official title: A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Doses of Intrathecally Administered ISIS 443139 in Patients With Early Manifest Huntington's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Huntington's Disease
Keywords: Huntington's Disease
HTTRx
Early Manifest Huntington's Disease
Lead sponsor: Ionis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2015-08-10
Enrollment: 46
Sex: ALL
Minimum age (years): 25
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study tested the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending doses of ISIS 443139 administered intrathecally to adult participants with early manifest Huntington's Disease.


Eligibility criteria: Key Inclusion Criteria:

* Diagnosed with early manifest Huntington's disease
* Male or female, aged 25 to 65 years, inclusive, at the time of informed consent
* Able and willing to meet all study requirements, including travel to Study Center and participation in all procedures and measurements at study visits
* Have a trial partner who is reliable, competent and at least 18 years of age, is willing to accompany the participant to select trial visits and to be available to the Study Center by phone if needed
* Able to tolerate MRI scans, blood draws and lumbar punctures
* Reside within 4 hours travel of the Study Center

Key Exclusion Criteria:

* Clinically significant medical condition, such as severe chorea, active suicidal ideation or any other conditions which would make the participant unsuitable for inclusion or could interfere with the participant participating in or completing the study
* Recent treatment with another investigational drug, biological agent, or device
* Prior treatment with an antisense oligonucleotide \[including small interfering ribonucleic acid (siRNA)\]
* Any history of gene therapy or cell transplantation or any other experimental brain surgery
* Presence of an implanted shunt for the drainage of cerebrospinal fluid (CSF) or an implanted central nervous system (CNS) catheter
* History of post-lumbar-puncture headache of moderate or severe intensity and/or blood patch
* Malignancy within 5 years of Screening, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated
* Hospitalization for any major medical or surgical procedure involving general anesthesia within 12 weeks of Screening or planned during the study

Primary outcomes:
measure: Number of Participants With Treatment-related Adverse Events (TEAEs)
timeFrame: Up to approximately 28 weeks
Secondary outcomes:
measure: Observed Cerebrospinal Fluid (CSF) Concentration for ISIS 443139
timeFrame: Days 1, 29, 57, 85, and 113 or 141
Other outcomes:
measure: Maximum Plasma Concentration (Cmax) for ISIS 443139
timeFrame: Days 1 and 85
measure: Time to Maximum Plasma Concentration (Tmax) for ISIS 443139
timeFrame: Days 1 and 85
measure: Change From Baseline in CSF Mutant Huntingtin (fM) Protein Concentration
timeFrame: Baseline to Final Assessment (Day 85 or 113)
measure: Change From Baseline in CSF Neurofilament Light Chain Concentration
timeFrame: Baseline to Final Assessment (Day 85 or 113)
measure: Ventricular Volume as Assessed by Structural Magnetic Resonance Imaging (MRI)
timeFrame: Screening, Days 113, and 197
measure: Huntington's Disease (HD) Cognitive Assessment Battery Composite Score
timeFrame: Baseline to Days 84, 141, and 197
Locations:
city: Vancouver
country: Canada
facility: University of British Columbia
state: British Columbia
city: Berlin
country: Germany
facility: Charite University Berlin
city: Bochum
country: Germany
facility: Ruhr-University of Bochum
city: Ulm
country: Germany
facility: Ulm University Hospital
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospital
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
city: London
country: United Kingdom
facility: University College London
city: Manchester
country: United Kingdom
facility: University of Manchester, St. Mary's Hospital
Study officials:
References:
citation: Rodrigues FB, Ferreira JJ, Wild EJ. Huntington's Disease Clinical Trials Corner: June 2019. J Huntingtons Dis. 2019;8(3):363-371. doi: 10.3233/JHD-199003.
citation: Tabrizi SJ, Leavitt BR, Landwehrmeyer GB, Wild EJ, Saft C, Barker RA, Blair NF, Craufurd D, Priller J, Rickards H, Rosser A, Kordasiewicz HB, Czech C, Swayze EE, Norris DA, Baumann T, Gerlach I, Schobel SA, Paz E, Smith AV, Bennett CF, Lane RM; Phase 1-2a IONIS-HTTRx Study Site Teams. Targeting Huntingtin Expression in Patients with Huntington's Disease. N Engl J Med. 2019 Jun 13;380(24):2307-2316. doi: 10.1056/NEJMoa1900907. Epub 2019 May 6.
citation: Rodrigues FB, Wild EJ. Huntington's Disease Clinical Trials Corner: February 2018. J Huntingtons Dis. 2018;7(1):89-98. doi: 10.3233/JHD-189001.