A Randomized, Double-Blind, Placebo-Controlled Study, Followed by an Open-Label Extension, to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Doses of Intrathecally Administered ISIS 814907 in Patients With Mild Alzheimer's Disease
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Ionis Pharmaceuticals, Inc.
- Enrollment
- 46
- Locations
- 13
- Primary Endpoint
- Part 1: Number of Participants With Adverse Events That Are Related to Treatment With ISIS 814907
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Other
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 50 Years to 74 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Part 1: Cohort A: ISIS 814907 10 mg
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.
Intervention: IONIS MAPTRx (Drug)
Part 1: Cohort B: ISIS 814907 30 mg
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.
Intervention: IONIS MAPTRx (Drug)
Part 1: Cohort C: ISIS 814907 60 mg
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.
Intervention: IONIS MAPTRx (Drug)
Part 1: Cohort D: ISIS 814907 115 mg
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.
Intervention: IONIS MAPTRx (Drug)
Part 1: Pooled 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.
Intervention: Placebo (Other)
Part 2: Late Start Cohort A + Cohort B + Cohort C + ISIS 814907 60 mg
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.
Intervention: IONIS MAPTRx (Drug)
Part 2: Late Start Cohort D + ISIS 814907 115 mg
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.
Intervention: IONIS MAPTRx (Drug)
Part 2: Early Start Cohort A + ISIS 814907 60 mg
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.
Intervention: IONIS MAPTRx (Drug)
Part 2: Early Start Cohort B + ISIS 814907 60 mg
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.
Intervention: IONIS MAPTRx (Drug)
Part 2: Early Start Cohort C + ISIS 814907 60 mg
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.
Intervention: IONIS MAPTRx (Drug)
Part 2: Early Start Cohort D + ISIS 814907 115 mg
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.
Intervention: IONIS MAPTRx (Drug)
Outcomes
Primary Outcomes
Part 1: Number of Participants With Adverse Events That Are Related to Treatment With ISIS 814907
Time Frame: 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
Time Frame: 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 Outcomes
- 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)