Modulating ApoE Signalling to Reduce Brain Inflammation, deLirium and postopErative Cognitive Dysfunction

NCT03802396 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: Pro00088855
• Study Type: interventional
• Target: 203
• Locations: 1 country
• Sites: 1

Brief Summary

This research study will evaluate the effectiveness and estimate the feasibility of administering an investigational drug called 'CN-105' (the study drug), to prevent postoperative cognitive decline, delirium (serious confusion) and underlying brain inflammatory and brain activity changes in adults 60 years and older undergoing surgery.

Conditions

Postoperative Delirium; Postoperative Cognitive Dysfunction

Keywords

Delirium; Aging; Elderly; Postoperative; Cognitive Dysfunction

Outcome Measures

Primary Outcomes (1)

• Number of Adverse Events (AEs) of Grade II or Higher Per Patient

  Safety of CN-105 administration, as measured by adverse event (AE) rates of Grade II and higher in CN-105 versus placebo-treated patients.

  up to 6-week follow-up

Secondary Outcomes (8)

• Change in Cerebrospinal Fluid (CSF) IL-6 Cytokine Levels Between Drug vs Placebo Treated Patients

  Baseline, 24 hours, approximately 6 weeks

• Change in CSF IL-8 Cytokine Levels Between Drug vs Placebo Treated Patients

  Baseline, 24 hours, approximately 6 weeks

• Change in CSF MCP-1 Cytokine Levels Between Drug vs Placebo Treated Patients

  Baseline, 24 hours, approximately 6 weeks

• Change in CSF G-CSF Cytokine Levels Between Drug vs Placebo Treated Patients

  Baseline, 24 hours, approximately 6 weeks

• Change in Cognitive Change Index (CCI) Between Drug vs Placebo Treated Patients

  Baseline, approximately 6 weeks

Study Arms (2)

CN-105

EXPERIMENTAL

Cohort 1: 50 Patients Dose of CN-105: 0.1 mg/kg Cohort 2: 50 Patients Dose of CN-105: 0.5 mg/kg Cohort 3: 50 Patients Dose of CN-105: 1 mg/kg

Drug: CN-105

Placebo

PLACEBO COMPARATOR

Cohort 1: 17 Patients receiving placebo Cohort 2: 17 Patients receiving placebo Cohort 3: 17 Patients receiving placebo

Drug: Placebo

Interventions

CN-105 DRUG

Three doses of CN-105 will be used in three successive cohorts of 50 patients each. 0.1 mg/kg (cohort 1), 0.5 mg/kg (cohort 2), 1 mg/kg (cohort 3) The study drug will be administered by IV every 6 hours, beginning 1 hour prior to surgery, until postoperative day 3 or hospital discharge, whichever occurs first, up to a maximum of 13 doses.

CN-105

Placebo DRUG

Patients will receive placebo intravenously every 6 hours, beginning 1 hour prior to surgery, until postoperative day 3 or hospital discharge, whichever occurs first, up to a maximum of 13 doses, identical to those receiving the study drug.

Placebo

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 60
• Ability to speak English
• Undergoing non-cardiac, non-neurologic surgical procedures; surgery scheduled to last \> 2 hours; due to be admitted to the hospital following surgery

You may not qualify if:

• Inmate of a correctional facility
• Scheduled to receive systemic chemotherapy between the time of the two cognitive testing sessions
• Known inability to undergo LPs due to anticoagulant use, severe anxiety, or other clinical contraindication known ahead of time.
• If a patient undergoes major head trauma that occurs between the times of the two cognitive testing sessions, then they will be withdrawn from the study.

Sponsors & Collaborators

• Miles Berger, MD PhD: lead

Study Sites (1)

Duke University Hospital

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Emergence Delirium; Postoperative Cognitive Complications; Delirium; Cognitive Dysfunction

Interventions

apolipoprotein E mimetic peptide CN-105

Condition Hierarchy (Ancestors)

Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Cognition Disorders

Results Point of Contact

• Title: Miles Berger, MD, PhD
• Organization: Duke University

miles.berger@duke.edu

919-684-8679

Study Officials

• Miles Berger, MD, PhD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants will be randomized to receive either CN-105 or placebo after they consent to participate in the trial. Participants will be enrolled in 1 of 3 dose cohorts of 67 subjects each. An independent statistician will prepare dose stratified mixed block size randomization lists in a 3 to 1 ratio to achieve the desired distribution of drug and placebo. In each block of 67 trial participants, 50 will receive CN-105 and 17 will receive placebo, in a double-blind fashion. CN-105 and placebo will be prepared in identical bags labelled simply with the trial participant's number (1-201) to keep all trial staff and clinicians blinded to randomization. Only the investigational pharmacist will have the randomization list for each participant showing what dose of CN-105 or placebo will be administered. To minimize bias, investigators conducting the laboratory assays on the CSF and blood samples will be blinded to trial group assignment during the course of the trial.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor, Neuroanesthesiology Division, Anesthesiology Department

Model Details: Investigators will enroll 201 patients total in this phase 2 escalating dose study, with escalating CN-105 doses occurring in three successive groups of 67 patients each. In each group of 67 patients, 50 will receive a given dose of CN-105 and 17 will receive placebo.

Study Record Dates

• First Submitted: January 10, 2019
• First Posted: January 14, 2019
• Study Start: July 15, 2018
• Primary Completion: December 28, 2022
• Study Completion: December 28, 2022
• Last Updated: October 16, 2024
• Results First Posted: September 4, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)