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Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IONIS-MAPTRx in Patients With Mild Alzheimer's Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03186989
Recruitment Status : Active, not recruiting
First Posted : June 14, 2017
Last Update Posted : February 7, 2020
Sponsor:
Information provided by (Responsible Party):
Ionis Pharmaceuticals, Inc.

Brief Summary:
The purpose is to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of IONIS-MAPTRx in patients with Mild Alzheimer's Disease

Condition or disease Intervention/treatment Phase
Mild Alzheimer's Disease Drug: IONIS MAPTRx Other: Placebo Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 46 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Other
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
Actual Study Start Date : June 5, 2017
Estimated Primary Completion Date : May 2022
Estimated Study Completion Date : May 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: IONIS-MAPTRx
IONIS MAPTRx (Study Drug)
Drug: IONIS MAPTRx

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.

Other Name: ISIS 814907

Placebo Comparator: Placebo
Artificial CSF
Other: Placebo
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 Measures :
  1. Incidence and severity of adverse events that are related to treatment with IONIS MAPTRx [ Time Frame: Up to Week 72 of Part 2 ]
    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 :
  1. Pharmacokinetics (PK) after ascending dose-levels of multiple IT bolus administrations of IONIS MAPTRx (trough concentration) [ Time Frame: Up to Week 72 of Part 2 ]
    The cerebrospinal fluid (CSF) trough concentrations of IONIS MAPTRx will be assessed after ascending dose-levels of multiple IT bolus administrations of IONIS MAPTRx

  2. Pharmacokinetics (PK) after ascending dose-levels of multiple IT bolus administrations of IONIS MAPTRx (maximum observed drug concentration or Cmax) [ Time Frame: Up to Week 72 of Part 2 ]
    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

  3. Pharmacokinetics after ascending dose-levels of multiple IT bolus administrations on IONIS MAPTRx (time taken to reach maximal concentration or Tmax) [ Time Frame: Up to Week 72 of Part 2 ]
    The plasma pharmacokinetics (time taken to reach maximal concentration or Tmax) of IONIS MAPTRx will be assessed following single and multiple dose IT administration

  4. Pharmacokinetics after ascending dose-levels of multiple IT bolus administrations on IONIS MAPTRx (Plasma terminal elimination half-life (t1/2λz) [ Time Frame: Up to Week 72 of Part 2 ]
    The plasma pharmacokinetics (Plasma terminal elimination half-life (t1/2λz) of IONIS-MAPTRx will be assessed following single and multiple dose IT administration

  5. 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) [ Time Frame: Up to Week 72 of Part 2 ]
    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



Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years to 74 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03186989


Locations
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Canada
Montreal Neurological Hospital
Montréal, Canada
Finland
Clinical Research Services Turku CRST
Turku, Finland
Germany
St Josef Hospital
Bochum, Germany
Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE)
Bonn, Germany, 53127
MVZ Mittweida Gbr
Mittweida, Germany
Universittsklinikum Ulm
Ulm, Germany
Netherlands
VU University Medical Center
Amsterdam, Netherlands, 1081 HV
QPS Netherlands BV
Groningen, Netherlands, 9713 AG
Sweden
Minnesmottagningen
Mölndal, Sweden
Karolinska University Hospital Huddinge
Stockholm, Sweden
United Kingdom
Royal Liverpool University Hospital
Liverpool, United Kingdom
University College London Hospitals NHS Foundation Trust
London, United Kingdom
Sheffield Institute for Translational Neuroscience (SITraN)
Sheffield, United Kingdom
Sponsors and Collaborators
Ionis Pharmaceuticals, Inc.
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Responsible Party: Ionis Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT03186989    
Other Study ID Numbers: ISIS 814907-CS1
NL60032.000.16 ( Other Identifier: CCMO )
2016-002713-22 ( EudraCT Number )
First Posted: June 14, 2017    Key Record Dates
Last Update Posted: February 7, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Ionis Pharmaceuticals, Inc.:
Mild Alzheimer's Disease
ISIS 814907
Memory Loss
Alzheimers
MAPT
Additional relevant MeSH terms:
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Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders