Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IONIS-MAPTRx in Patients With Mild Alzheimer's Disease
- Registration Number
- NCT03186989
- Lead Sponsor
- Ionis Pharmaceuticals, Inc.
- Brief Summary
The purpose of this study was to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of IONIS-MAPTRx in patients with Mild Alzheimer's Disease.
- Detailed Description
This was a randomized, double-blind, placebo-controlled study in 46 participants, followed by an Open-Label Extension. This study consisted of two parts:
Part 1: a randomized, double-blind, placebo-controlled multiple ascending dose period in participants with Mild Alzheimer's Disease, followed by Part 2: the open-label, long-term extension period.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 46
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 1: Cohort A: ISIS 814907 10 mg IONIS MAPTRx Participants received 10 milligrams (mg) ISIS 814907 diluted in 20 milliliters (mL) artificial cerebrospinal fluid (CSF), intrathecally, every four weeks (Q4W) on Days 1, 29, 57, and 85 in Part 1 of the study. Part 1: Cohort B: ISIS 814907 30 mg IONIS MAPTRx Participants received 30 mg ISIS 814907 diluted in 20 mL in artificial CSF, intrathecally, Q4W on Days 1, 29, 57, and 85 in Part 1 of the study. Part 1: Cohort C: ISIS 814907 60 mg IONIS MAPTRx Participants received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q4W on Days 1, 29, 57, and 85 in Part 1 of the study. Part 2: Late Start Cohort D + ISIS 814907 115 mg IONIS MAPTRx Participants from MAD Cohort D that were placebo-treated, received 115 mg ISIS 814907 diluted up in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study. Part 1: Cohort D: ISIS 814907 115 mg IONIS MAPTRx Participants received 115 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, every 12 weeks (Q12W) on Days 1 and 85 in Part 1 of the study. Part 2: Early Start Cohort C + ISIS 814907 60 mg IONIS MAPTRx Participants from MAD Cohort C that were ISIS 814907 60 mg-treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study. Part 1: Pooled Placebo Placebo Participants received 20 mL artificial CSF, intrathecally, as placebo on Days 1, 29, 57, and 85 for the 4-dose regimens, or on Days 1 and 85 for the 2-dose regimens in Part 1 of the study. Part 2: Late Start Cohort A + Cohort B + Cohort C + ISIS 814907 60 mg IONIS MAPTRx Participants from MAD Cohorts A, B, C that were placebo-treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study. Part 2: Early Start Cohort A + ISIS 814907 60 mg IONIS MAPTRx Participants from MAD Cohort A that were ISIS 814907 10 mg -treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study. Part 2: Early Start Cohort B + ISIS 814907 60 mg IONIS MAPTRx Participants from MAD Cohort B that were ISIS 814907 30 mg-treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study. Part 2: Early Start Cohort D + ISIS 814907 115 mg IONIS MAPTRx Participants from MAD Cohort D that were ISIS 814907 115 mg-treated, received 115 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
- Primary Outcome Measures
Name Time Method Part 1: Number of Participants With Adverse Events That Are Related to Treatment With ISIS 814907 From first dose of study drug up to Week 37 in Part 1 An adverse event (AE) was defined as any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of medicinal (investigational) product, whether or not the AE was considered related to the medicinal (investigational) product. A TEAE was defined as any AE that starts or worsens on or after the date of first dose of study treatment. TEAEs were categorised as mild, moderate, and severe to aid in severity assessment.
Part 2: Number of Participants With Adverse Events That Are Related to Treatment With ISIS 814907 From first dose of study drug up to Week 64 in Part 2 An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of medicinal (investigational) product, whether or not the AE was considered related to the medicinal (investigational) product. A TEAE was defined as any AE that starts or worsens on or after the date of first dose of study treatment. TEAEs were categorised as mild, moderate, and severe to aid in severity assessment.
- Secondary Outcome Measures
Name Time Method CSF Trough Concentration of ISIS 814907 Pre dose on Day 85 in Part 1 and Day 337 in Part 2 Maximum Observed Drug Concentration (Cmax) of ISIS 814907 in Plasma Pre-dose, 0.5, 1, 2, 3, 4, and 5 hours post-intrathecal (IT) bolus injection on Day 85 in Part 1 and on Day 337 in Part 2 Time Taken to Reach Maximal Concentration (Tmax) of ISIS 814907 in Plasma Pre-dose, 0.5, 1, 2, 3, 4, and 5 hours post-IT bolus injection on Day 85 in Part 1 and on Day 337 in Part 2 Terminal Elimination Half-life (t1/2λz) of ISIS 814907 in Plasma Pre-dose, 0.5, 1, 2, 3, 4, and 5 hours post-IT bolus injection on Day 85 in Part 1 and on Day 337 in Part 2 Areas Under the Plasma Concentration-time Curve From Zero Time (Predose) to 24 Hours After the IT Administration (AUC0-24h) of ISIS 814907 Pre-dose, 0.5, 1, 2, 3, 4, and 5 hours post-IT bolus injection on Day 85 in Part 1 and on Day 337 in Part 2
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Trial Locations
- Locations (13)
Karolinska University Hospital Huddinge
🇸🇪Stockholm, Sweden
Clinical Research Services Turku CRST
🇫🇮Turku, Finland
University College London Hospitals NHS Foundation Trust
🇬🇧London, United Kingdom
Sheffield Institute for Translational Neuroscience (SITraN)
🇬🇧Sheffield, United Kingdom
Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE)
🇩🇪Bonn, Germany
Montreal Neurological Hospital
🇨🇦Montréal, Canada
St Josef Hospital
🇩🇪Bochum, Germany
MVZ Mittweida Gbr
🇩🇪Mittweida, Germany
Universittsklinikum Ulm
🇩🇪Ulm, Germany
VU University Medical Center
🇳🇱Amsterdam, Netherlands
QPS Netherlands BV
🇳🇱Groningen, Netherlands
Minnesmottagningen
🇸🇪Mölndal, Sweden
Royal Liverpool University Hospital
🇬🇧Liverpool, United Kingdom