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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03186989
Other study ID # ISIS 814907-CS1
Secondary ID NL60032.000.1620
Status Completed
Phase Phase 1/Phase 2
First received
Last updated
Start date October 12, 2017
Est. completion date May 13, 2022

Study information

Verified date February 2023
Source Ionis Pharmaceuticals, Inc.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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


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.


Recruitment information / eligibility

Status Completed
Enrollment 46
Est. completion date May 13, 2022
Est. primary completion date May 12, 2022
Accepts healthy volunteers No
Gender All
Age group 50 Years to 74 Years
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

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 weeks.
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.

Locations

Country Name City State
Canada Montreal Neurological Hospital Montréal
Finland Clinical Research Services Turku CRST Turku
Germany St Josef Hospital Bochum
Germany Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Bonn
Germany MVZ Mittweida Gbr Mittweida
Germany Universittsklinikum Ulm Ulm
Netherlands VU University Medical Center Amsterdam
Netherlands QPS Netherlands BV Groningen
Sweden Minnesmottagningen Mölndal
Sweden Karolinska University Hospital Huddinge Stockholm
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

Sponsors (1)

Lead Sponsor Collaborator
Ionis Pharmaceuticals, Inc.

Countries where clinical trial is conducted

Canada,  Finland,  Germany,  Netherlands,  Sweden,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 Up to Week 72 of Part 2
Secondary 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 Up to Week 72 of Part 2
Secondary 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 Up to Week 72 of Part 2
Secondary 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 Up to Week 72 of Part 2
Secondary Pharmacokinetics after ascending dose-levels of multiple IT bolus administrations on IONIS MAPTRx (Plasma terminal elimination half-life (t1/2?z) The plasma pharmacokinetics (Plasma terminal elimination half-life (t1/2?z) of IONIS-MAPTRx will be assessed following single and multiple dose IT administration Up to Week 72 of Part 2
Secondary 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 Up to Week 72 of Part 2
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