Back to resultsSafety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IONIS-MAPTRx in Patients With Mild Alzheimer's Disease
Primary Purpose
Mild Alzheimer's Disease
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
IONIS MAPTRx
Placebo
Sponsored by
About this trial
This is an interventional other trial for Mild Alzheimer's Disease focused on measuring Mild Alzheimer's Disease, ISIS 814907, Memory Loss, Alzheimers, MAPT
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
Sites / Locations
- Montreal Neurological Hospital
- Clinical Research Services Turku CRST
- St Josef Hospital
- Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE)
- MVZ Mittweida Gbr
- Universittsklinikum Ulm
- VU University Medical Center
- QPS Netherlands BV
- Minnesmottagningen
- Karolinska University Hospital Huddinge
- Royal Liverpool University Hospital
- University College London Hospitals NHS Foundation Trust
- Sheffield Institute for Translational Neuroscience (SITraN)
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
IONIS-MAPTRx
Placebo
Arm Description
IONIS MAPTRx (Study Drug)
Artificial CSF
Outcomes
Primary Outcome Measures
Incidence and severity of adverse events that are related to treatment with IONIS MAPTRx
The safety and tolerability of ascending dose-levels of multiple IT bolus administrations of IONIS MAPTRx will be assessed by determining the incidence, severity, and dose relationship of adverse events that are related to treatment with IONIS MAPTRx
Secondary Outcome Measures
Pharmacokinetics (PK) after ascending dose-levels of multiple IT bolus administrations of IONIS MAPTRx (trough concentration)
The cerebrospinal fluid (CSF) trough concentrations of IONIS MAPTRx will be assessed after ascending dose-levels of multiple IT bolus administrations of IONIS MAPTRx
Pharmacokinetics (PK) after ascending dose-levels of multiple IT bolus administrations of IONIS MAPTRx (maximum observed drug concentration or Cmax)
The Plasma pharmacokinetics (maximum observed drug concentration or Cmax)) of IONIS MAPTRx will be assessed after ascending dose-levels of multiple IT bolus administrations of IONIS MAPTRx
Pharmacokinetics after ascending dose-levels of multiple IT bolus administrations on IONIS MAPTRx (time taken to reach maximal concentration or Tmax)
The plasma pharmacokinetics (time taken to reach maximal concentration or Tmax) of IONIS MAPTRx will be assessed following single and multiple dose IT administration
Pharmacokinetics after ascending dose-levels of multiple IT bolus administrations on IONIS MAPTRx (Plasma terminal elimination half-life (t1/2λz)
The plasma pharmacokinetics (Plasma terminal elimination half-life (t1/2λz) of IONIS-MAPTRx will be assessed following single and multiple dose IT administration
Pharmacokinetics after ascending dose-levels of multiple IT bolus administrations on IONIS MAPTRx (Partial areas under the plasma concentration-time curve from zero time (predose) to selected times (t) after the IT administration (AUCt)
The plasma pharmacokinetics (Partial areas under the plasma concentration-time curve from zero time (predose) to selected times (t) after the IT administration (AUCt) of IONIS MAPTRx will be assessed following single and multiple dose IT administration
Full Information
NCT ID
NCT03186989
First Posted
June 6, 2017
Last Updated
February 16, 2023
Sponsor
Ionis Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT03186989
Brief Title
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
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Completed
Study Start Date
October 12, 2017 (Actual)
Primary Completion Date
May 12, 2022 (Actual)
Study Completion Date
May 13, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ionis Pharmaceuticals, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose is to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of IONIS-MAPTRx in patients with Mild Alzheimer's Disease
Detailed Description
This is a randomized, double-blind, placebo-controlled study, followed by an Open-Label Extension in up to 44 participants. This study will consist in 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mild Alzheimer's Disease
Keywords
Mild Alzheimer's Disease, ISIS 814907, Memory Loss, Alzheimers, MAPT
7. Study Design
Primary Purpose
Other
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
46 (Actual)
8. Arms, Groups, and Interventions
Arm Title
IONIS-MAPTRx
Arm Type
Experimental
Arm Description
IONIS MAPTRx (Study Drug)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Artificial CSF
Intervention Type
Drug
Intervention Name(s)
IONIS MAPTRx
Other Intervention Name(s)
ISIS 814907
Intervention Description
Part 1: IONIS MAPTRx is administered intrathecally at 4 week intervals over the course of a 13 week treatment period for dose levels A, B, C, and D.
Part 2: IONIS MAPTRx is administered intrathecally at quarterly intervals for 48 weeks.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
A placebo is administered intrathecally at 4 week intervals over the course of 13 weeks in Part 1. No placebo is given in Part 2.
Primary Outcome Measure Information:
Title
Incidence and severity of adverse events that are related to treatment with IONIS MAPTRx
Description
The safety and tolerability of ascending dose-levels of multiple IT bolus administrations of IONIS MAPTRx will be assessed by determining the incidence, severity, and dose relationship of adverse events that are related to treatment with IONIS MAPTRx
Time Frame
Up to Week 72 of Part 2
Secondary Outcome Measure Information:
Title
Pharmacokinetics (PK) after ascending dose-levels of multiple IT bolus administrations of IONIS MAPTRx (trough concentration)
Description
The cerebrospinal fluid (CSF) trough concentrations of IONIS MAPTRx will be assessed after ascending dose-levels of multiple IT bolus administrations of IONIS MAPTRx
Time Frame
Up to Week 72 of Part 2
Title
Pharmacokinetics (PK) after ascending dose-levels of multiple IT bolus administrations of IONIS MAPTRx (maximum observed drug concentration or Cmax)
Description
The Plasma pharmacokinetics (maximum observed drug concentration or Cmax)) of IONIS MAPTRx will be assessed after ascending dose-levels of multiple IT bolus administrations of IONIS MAPTRx
Time Frame
Up to Week 72 of Part 2
Title
Pharmacokinetics after ascending dose-levels of multiple IT bolus administrations on IONIS MAPTRx (time taken to reach maximal concentration or Tmax)
Description
The plasma pharmacokinetics (time taken to reach maximal concentration or Tmax) of IONIS MAPTRx will be assessed following single and multiple dose IT administration
Time Frame
Up to Week 72 of Part 2
Title
Pharmacokinetics after ascending dose-levels of multiple IT bolus administrations on IONIS MAPTRx (Plasma terminal elimination half-life (t1/2λz)
Description
The plasma pharmacokinetics (Plasma terminal elimination half-life (t1/2λz) of IONIS-MAPTRx will be assessed following single and multiple dose IT administration
Time Frame
Up to Week 72 of Part 2
Title
Pharmacokinetics after ascending dose-levels of multiple IT bolus administrations on IONIS MAPTRx (Partial areas under the plasma concentration-time curve from zero time (predose) to selected times (t) after the IT administration (AUCt)
Description
The plasma pharmacokinetics (Partial areas under the plasma concentration-time curve from zero time (predose) to selected times (t) after the IT administration (AUCt) of IONIS MAPTRx will be assessed following single and multiple dose IT administration
Time Frame
Up to Week 72 of Part 2
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
74 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
Montreal Neurological Hospital
City
Montréal
Country
Canada
Facility Name
Clinical Research Services Turku CRST
City
Turku
Country
Finland
Facility Name
St Josef Hospital
City
Bochum
Country
Germany
Facility Name
Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE)
City
Bonn
ZIP/Postal Code
53127
Country
Germany
Facility Name
MVZ Mittweida Gbr
City
Mittweida
Country
Germany
Facility Name
Universittsklinikum Ulm
City
Ulm
Country
Germany
Facility Name
VU University Medical Center
City
Amsterdam
ZIP/Postal Code
1081 HV
Country
Netherlands
Facility Name
QPS Netherlands BV
City
Groningen
ZIP/Postal Code
9713 AG
Country
Netherlands
Facility Name
Minnesmottagningen
City
Mölndal
Country
Sweden
Facility Name
Karolinska University Hospital Huddinge
City
Stockholm
Country
Sweden
Facility Name
Royal Liverpool University Hospital
City
Liverpool
Country
United Kingdom
Facility Name
University College London Hospitals NHS Foundation Trust
City
London
Country
United Kingdom
Facility Name
Sheffield Institute for Translational Neuroscience (SITraN)
City
Sheffield
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IONIS-MAPTRx in Patients With Mild Alzheimer's Disease
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