Clinical trial NCT03186989: Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IONIS-MAPTRx in Patients With Mild Alzheimer's Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Mild Alzheimer's Disease
Keywords: Mild Alzheimer's Disease
ISIS 814907
Memory Loss
Alzheimers
MAPT
Tau
Lead sponsor: Ionis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2017-06-14
Enrollment: 46
Sex: ALL
Minimum age (years): 50
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Eligibility criteria: Inclusion Criteria for Part 1:

* Males or females aged 50-74 years, inclusive, at the time of informed consent
* Diagnosed with mild Alzheimers disease, including CSF biomarkers consistent with this diagnosis
* Body Mass Index BMI ≥ 18 and ≤ 35 kg/m2 and total body weight \> 50 kg (110 lbs)
* Able and willing to meet all study requirements, including toleration for MRI scans, blood draws and lumbar punctures, 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 patient to select trial visits and to be available to the Study Center by phone if needed
* Reside within 4 hours travel of the Study Center

Exclusion Criteria for Part 1:

* Treatment with another Study Drug, biological agent, or device within one-month of Screening or 5 half-lives of investigational agent, whichever is longer
* Clinically significant medical condition which would make the patient unsuitable for inclusion or could interfere with the patient participating in or completing the study
* Use of a disallowed CNS-active or antipsychotic medication within 4 weeks prior to Screening punctures

Inclusion Criteria for Part 2:

* Must have completed the Treatment Evaluation and Post-Treatment Periods in Part 1

Exclusion Criteria for Part 2 (only applicable to participants in Cohorts A and B, as participants from Cohorts C and D will seamlessly transition to Part 2):

* Treatment with another Study Drug, biological agent, or device within one-month of Screening or 5 half-lives of investigational agent, whichever is longer
* Clinically significant medical condition which would make the patient unsuitable for inclusion or could interfere with the patient participating in or completing the study
* Use of a disallowed CNS-active or antipsychotic medication within 4 weeks prior to Screening punctures

Primary outcomes:
measure: Part 1: Number of Participants With Adverse Events That Are Related to Treatment With ISIS 814907
timeFrame: From first dose of study drug up to Week 37 in Part 1
measure: Part 2: Number of Participants With Adverse Events That Are Related to Treatment With ISIS 814907
timeFrame: From first dose of study drug up to Week 64 in Part 2
Secondary outcomes:
measure: CSF Trough Concentration of ISIS 814907
timeFrame: Pre dose on Day 85 in Part 1 and Day 337 in Part 2
measure: Maximum Observed Drug Concentration (Cmax) of ISIS 814907 in Plasma
timeFrame: 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
measure: Time Taken to Reach Maximal Concentration (Tmax) of ISIS 814907 in Plasma
timeFrame: 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
measure: Terminal Elimination Half-life (t1/2λz) of ISIS 814907 in Plasma
timeFrame: 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
measure: Areas Under the Plasma Concentration-time Curve From Zero Time (Predose) to 24 Hours After the IT Administration (AUC0-24h) of ISIS 814907
timeFrame: 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
Other outcomes:
Locations:
city: Montréal
country: Canada
facility: Montreal Neurological Hospital
city: Turku
country: Finland
facility: Clinical Research Services Turku CRST
city: Bochum
country: Germany
facility: St Josef Hospital
city: Bonn
country: Germany
facility: Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE)
city: Mittweida
country: Germany
facility: MVZ Mittweida Gbr
city: Ulm
country: Germany
facility: Universittsklinikum Ulm
city: Amsterdam
country: Netherlands
facility: VU University Medical Center
city: Groningen
country: Netherlands
facility: QPS Netherlands BV
city: Mölndal
country: Sweden
facility: Minnesmottagningen
city: Stockholm
country: Sweden
facility: Karolinska University Hospital Huddinge
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust
city: Sheffield
country: United Kingdom
facility: Sheffield Institute for Translational Neuroscience (SITraN)
Study officials:
References: