Safety, Tolerability, and Pharmacokinetics of C2N-8E12 in Subjects With Progressive Supranuclear Palsy

NCT ID: NCT02494024

Last Updated: 2017-07-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

32 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-07-31

Study Completion Date

2016-08-31

Brief Summary

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This study will evaluate the safety and tolerability (maximum tolerated dose (MTD) within the specified dosing range) of single intravenous (IV) infusion of C2N-8E12 in patients with progressive supranuclear palsy (PSP).

Detailed Description

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This study evaluates the safety, tolerability, pharmacokinetics, and maximum tolerated dose (within dosing range) of intravenous (IV) infusion of C2N-8E12 in 32 patients with progressive supranuclear palsy (PSP). Four sequential cohorts will receive increasing single doses of either C2N-8E12 or placebo. Out of every 4 patients enrolled 3 patients will receive drug and 1 will receive placebo. Study participants will be followed for a minimum of 2 months post-treatment to monitor for the safety, tolerability, pharmacokinetics, and immunogenicity of C2N-8E12.

Conditions

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Progressive Supranuclear Palsy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Single dose C2N-8E12 level 1

Single IV infusion of C2N-8E12

Group Type EXPERIMENTAL

Single dose C2N-8E12

Intervention Type DRUG

C2N-8E12 is a humanized recombinant anti-human tau antibody.

Single dose C2N-8E12 level 2

Single IV infusion of C2N-8E12

Group Type EXPERIMENTAL

Single dose C2N-8E12

Intervention Type DRUG

C2N-8E12 is a humanized recombinant anti-human tau antibody.

Single dose C2N-8E12 level 3

Single IV infusion of C2N-8E12

Group Type EXPERIMENTAL

Single dose C2N-8E12

Intervention Type DRUG

C2N-8E12 is a humanized recombinant anti-human tau antibody.

Single dose C2N-8E12 level 4

Single IV infusion of C2N-8E12

Group Type EXPERIMENTAL

Single dose C2N-8E12

Intervention Type DRUG

C2N-8E12 is a humanized recombinant anti-human tau antibody.

Single dose placebo

Single IV infusion of placebo

Group Type PLACEBO_COMPARATOR

Single dose placebo

Intervention Type DRUG

Subjects will be block randomized to receive a single dose of C2N-8E12 or placebo in two blocks of 4 subjects (3:1, C2N-8E12:placebo) per cohort.

Interventions

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Single dose C2N-8E12

C2N-8E12 is a humanized recombinant anti-human tau antibody.

Intervention Type DRUG

Single dose placebo

Subjects will be block randomized to receive a single dose of C2N-8E12 or placebo in two blocks of 4 subjects (3:1, C2N-8E12:placebo) per cohort.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Meets NINDS-SPSP possible or probable criteria as modified for NNIPPS and AL-108-231 clinical trials
* Brain MRI at Screening is consistent with PSP;
* Stable medications for Parkinsonism for at least 2 months prior to Screening;
* Agree to use protocol specified methods of contraception.

Exclusion Criteria

* Signs of a progressive neurological disorder that better meets the criteria for types of neurological disorders other than PSP;
* Currently on any other biologic or immunomodulatory therapy;
* Subjects that reside at a skilled nursing or dementia care facility;
* Diagnosis of any other significant unrelated neurological or psychiatric disorders that could account for cognitive deficits;
* Untreated major depression at baseline evaluation, based on clinical judgment and results in geriatric depression scale;
* Unable to tolerate MRI scan at Screening or any other contraindication to MRI;
* Any contraindication to or unable to tolerate lumbar puncture at Screening, including use of anti-coagulant medications.
Minimum Eligible Age

50 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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C2N Diagnostics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Adam Boxer, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

UCSF Memory and Aging Center

Locations

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University of Alabama

Birmingham, Alabama, United States

Site Status

Mayo Clinic

Scottsdale, Arizona, United States

Site Status

University of California, Los Angeles (UCLA)

Los Angeles, California, United States

Site Status

UCSD Department of Neurosciences

San Diego, California, United States

Site Status

University of California, San Francisco

San Francisco, California, United States

Site Status

University of Florida College of Medicine

Gainesville, Florida, United States

Site Status

Mayo Clinic

Jacksonville, Florida, United States

Site Status

Indiana University Medical Center

Indianapolis, Indiana, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Columbia University

New York, New York, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

Texas Health Presbyterian Dallas

Dallas, Texas, United States

Site Status

Countries

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United States

References

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Yanamandra K, Kfoury N, Jiang H, Mahan TE, Ma S, Maloney SE, Wozniak DF, Diamond MI, Holtzman DM. Anti-tau antibodies that block tau aggregate seeding in vitro markedly decrease pathology and improve cognition in vivo. Neuron. 2013 Oct 16;80(2):402-414. doi: 10.1016/j.neuron.2013.07.046. Epub 2013 Sep 26.

Reference Type BACKGROUND
PMID: 24075978 (View on PubMed)

Boxer AL, Lang AE, Grossman M, Knopman DS, Miller BL, Schneider LS, Doody RS, Lees A, Golbe LI, Williams DR, Corvol JC, Ludolph A, Burn D, Lorenzl S, Litvan I, Roberson ED, Hoglinger GU, Koestler M, Jack CR Jr, Van Deerlin V, Randolph C, Lobach IV, Heuer HW, Gozes I, Parker L, Whitaker S, Hirman J, Stewart AJ, Gold M, Morimoto BH; AL-108-231 Investigators. Davunetide in patients with progressive supranuclear palsy: a randomised, double-blind, placebo-controlled phase 2/3 trial. Lancet Neurol. 2014 Jul;13(7):676-85. doi: 10.1016/S1474-4422(14)70088-2. Epub 2014 May 27.

Reference Type BACKGROUND
PMID: 24873720 (View on PubMed)

Litvan I, Agid Y, Calne D, Campbell G, Dubois B, Duvoisin RC, Goetz CG, Golbe LI, Grafman J, Growdon JH, Hallett M, Jankovic J, Quinn NP, Tolosa E, Zee DS. Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): report of the NINDS-SPSP international workshop. Neurology. 1996 Jul;47(1):1-9. doi: 10.1212/wnl.47.1.1.

Reference Type BACKGROUND
PMID: 8710059 (View on PubMed)

Yanamandra K, Jiang H, Mahan TE, Maloney SE, Wozniak DF, Diamond MI, Holtzman DM. Anti-tau antibody reduces insoluble tau and decreases brain atrophy. Ann Clin Transl Neurol. 2015 Mar;2(3):278-88. doi: 10.1002/acn3.176. Epub 2015 Jan 23.

Reference Type BACKGROUND
PMID: 25815354 (View on PubMed)

Other Identifiers

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C2N-8E12-WW-104

Identifier Type: -

Identifier Source: org_study_id

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