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

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ClinicalTrials.gov Identifier: NCT03186989
Recruitment Status : Recruiting
First Posted : June 14, 2017
Last Update Posted : September 11, 2018
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:
Allocation: RandomizedEndpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment

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 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


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




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



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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:

  • 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:

  • 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


Contacts
Contact: Ionis Pharmaceuticals 800-679-4747 patients@ionisph.com

Locations
Canada
Montreal Neurological Hospital Recruiting
Montréal, Canada
Contact: Maxime Boutin-Caron    +1 514 398 5505    maxime.boutin-caron@mcgill.ca   
Principal Investigator: Angela Genge         
Finland
Clinical Research Services Turku CRST Recruiting
Turku, Finland
Contact: Anne Lithonius    358 2 4206 4712    anne.lithonius@crst.fi   
Germany
Charite - Universitaetsmedizin Berlin Campus Mitte Withdrawn
Berlin, Germany
St Josef Hospital Recruiting
Bochum, Germany
Contact: Barbara Kaminski    49 234 5092703    b.kaminski@klinikum-bochum.de   
Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Recruiting
Bonn, Germany, 53127
Contact: Claudia Lindlar    +49 228 43302 849    studienassistenten-Bonn@dzne.de   
Principal Investigator: Anja Schneider         
MVZ Mittweida Gbr Recruiting
Mittweida, Germany
Contact: Anne Merkel    +49 3727991006    merkel@mvz-mittweida.de   
Principal Investigator: Ralf Bodenschatz         
Universittsklinikum Ulm Recruiting
Ulm, Germany
Contact: Therese Poehler    +49 73150063089    therese.poehler@uni-ulm.de   
Principal Investigator: Christine Von Arnim         
Netherlands
Faculty Medical Sciences UMCG Neurology Recruiting
Groningen, Netherlands
Contact: Floor Morrien    +31 50 3048000    projectmanagement@qps.com   
Principal Investigator: Peter P De Deyn         
Sweden
Minnesmottagningen Recruiting
Mölndal, Sweden
Contact: Maria Berglund    +46 31 3438668    maria.a.berglund@vgregion.se   
Principal Investigator: Anne Borjesson-Hanson         
Karolinska University Hospital Huddinge Recruiting
Stockholm, Sweden
Contact: Ann-Christine Tysen Backstrom    +46 8 58585468    ann-christine.tysen-backstrom@sll.se   
Principal Investigator: Anne Borjesson-Hanson         
United Kingdom
Royal Liverpool University Hospital Recruiting
Liverpool, United Kingdom
Contact: Gladys Madzamba    +44 (0) 151 706 4860    Gladys.madzamba@rlbuht.nhs.uk   
Principal Investigator: Richard Fitzgerald         
University College London Hospitals NHS Foundation Trust Recruiting
London, United Kingdom
Contact: Philip Woodgate, M.D.    +44 02034484531    p.woodgate@ucl.ac.uk   
Principal Investigator: Cath Mummery         
Sheffield Institute for Translational Neuroscience (SITraN) Recruiting
Sheffield, United Kingdom
Contact: Kamel Bouakline    +44 01142713339    kamel.bouakline@sth.nhs.uk   
Principal Investigator: Daniel Blackburn         
Sponsors and Collaborators
Ionis Pharmaceuticals, Inc.

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: September 11, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders