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

Mild Alzheimer's Disease Clinical Trial

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

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
• 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
• 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

Related Conditions & MeSH terms

• Alzheimer Disease
• Mild Alzheimer's Disease

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