Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03186989
Recruitment Status : Recruiting
First Posted : June 14, 2017
Last Update Posted : August 26, 2019
Sponsor:
Information provided by (Responsible Party):
Ionis Pharmaceuticals, Inc.

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.


Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 44 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 : January 31, 2020
Estimated Study Completion Date : February 29, 2020

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Incidence and severity of adverse events that are related to treatment with IONIS MAPTRx [ Time Frame: Up to 253 Days ]
    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 253 days ]
    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 253 days ]
    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 253 days ]
    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 253 days ]
    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 253 days ]
    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


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
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
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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


Contacts
Layout table for location contacts
Contact: Ionis Pharmaceuticals 800-679-4747 patients@ionisph.com

Locations
Layout table for location information
Canada
Montreal Neurological Hospital Recruiting
Montréal, Canada
Contact    +1 514 398 5505    maxime.boutin-caron@mcgill.ca   
Finland
Clinical Research Services Turku CRST Recruiting
Turku, Finland
Contact    358 2 4206 4712    anne.lithonius@crst.fi   
Germany
Charite - Universitaetsmedizin Berlin Campus Mitte Withdrawn
Berlin, Germany
St Josef Hospital Recruiting
Bochum, Germany
Contact    49 234 5092703    b.kaminski@klinikum-bochum.de   
Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Recruiting
Bonn, Germany, 53127
Contact    +49 228 43302 849    studienassistenten-Bonn@dzne.de   
MVZ Mittweida Gbr Recruiting
Mittweida, Germany
Contact    +49 3727991006    merkel@mvz-mittweida.de   
Universittsklinikum Ulm Recruiting
Ulm, Germany
Contact    +49 73150063089    therese.poehler@uni-ulm.de   
Netherlands
VU University Medical Center Recruiting
Amsterdam, Netherlands, 1081 HV
Contact    +31 065 337 0401      
QPS Netherlands BV Recruiting
Groningen, Netherlands, 9713 AG
Contact    +31 50 3048000    projectmanagement@qps.com   
Sweden
Minnesmottagningen Completed
Mölndal, Sweden
Karolinska University Hospital Huddinge Recruiting
Stockholm, Sweden
Contact    +46 8 58585468    ann-christine.tysen-backstrom@sll.se   
United Kingdom
Royal Liverpool University Hospital Recruiting
Liverpool, United Kingdom
Contact    +44 (0) 151 706 4860    Gladys.madzamba@rlbuht.nhs.uk   
University College London Hospitals NHS Foundation Trust Recruiting
London, United Kingdom
Contact    +44 02034484531    p.woodgate@ucl.ac.uk   
Sheffield Institute for Translational Neuroscience (SITraN) Recruiting
Sheffield, United Kingdom
Contact    +44 01142713339    kamel.bouakline@sth.nhs.uk   
Sponsors and Collaborators
Ionis Pharmaceuticals, Inc.
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for additonal information
Responsible Party: Ionis Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT03186989     History of Changes
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: August 26, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
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:
Layout table for MeSH terms
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
 Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders