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

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ClinicalTrials.gov Identifier: NCT02494024

Recruitment Status : Completed

First Posted : July 10, 2015

Last Update Posted : July 26, 2017

Sponsor:

Information provided by (Responsible Party):

C2N Diagnostics

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Progressive Supranuclear Palsy	Drug: Single dose C2N-8E12 Drug: Single dose placebo	Phase 1

Detailed Description:

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	32 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	A Double-Blind, Placebo Controlled, Single Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of C2N-8E12 in Subjects With Progressive Supranuclear Palsy
Study Start Date :	July 2015
Actual Primary Completion Date :	August 2016
Actual Study Completion Date :	August 2016

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Progressive supranuclear palsy

MedlinePlus related topics: Paralysis Progressive Supranuclear Palsy

Genetic and Rare Diseases Information Center resources: Progressive Supranuclear Palsy

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Single dose C2N-8E12 level 1 Single IV infusion of C2N-8E12	Drug: Single dose C2N-8E12 C2N-8E12 is a humanized recombinant anti-human tau antibody.
Experimental: Single dose C2N-8E12 level 2 Single IV infusion of C2N-8E12	Drug: Single dose C2N-8E12 C2N-8E12 is a humanized recombinant anti-human tau antibody.
Experimental: Single dose C2N-8E12 level 3 Single IV infusion of C2N-8E12	Drug: Single dose C2N-8E12 C2N-8E12 is a humanized recombinant anti-human tau antibody.
Experimental: Single dose C2N-8E12 level 4 Single IV infusion of C2N-8E12	Drug: Single dose C2N-8E12 C2N-8E12 is a humanized recombinant anti-human tau antibody.
Placebo Comparator: Single dose placebo Single IV infusion of placebo	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.

Outcome Measures

Primary Outcome Measures :

Safety and tolerability, as measured by number of participants experiencing adverse events (AEs), serious AEs, and abnormalities in clinical laboratory tests, vital signs, ECGs, MRI, and physical and neurological exams. [ Time Frame: up to 4 months ]

Secondary Outcome Measures :

Immunogenicity as measured by the number of participants developing anti drug antibodies. [ Time Frame: up to 4 months ]
Area under the concentration vs time curve (AUC) of C2N-8E12 [ Time Frame: up to 4 months ]
Elimination half-life of C2N-8E12 [ Time Frame: up to 4 months ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	50 Years to 85 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Key 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.

Key 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.

Contacts and Locations

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): NCT02494024

Locations

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United States, Alabama
University of Alabama
Birmingham, Alabama, United States, 35294
United States, Arizona
Mayo Clinic
Scottsdale, Arizona, United States, 85259
United States, California
University of California, Los Angeles (UCLA)
Los Angeles, California, United States, 90095
UCSD Department of Neurosciences
San Diego, California, United States, 92037
University of California, San Francisco
San Francisco, California, United States, 94158
United States, Florida
University of Florida College of Medicine
Gainesville, Florida, United States, 32607
Mayo Clinic
Jacksonville, Florida, United States, 32224
United States, Indiana
Indiana University Medical Center
Indianapolis, Indiana, United States, 46202
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, New York
Columbia University
New York, New York, United States, 10032-3795
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232-2551
United States, Texas
Texas Health Presbyterian Dallas
Dallas, Texas, United States, 75231

Sponsors and Collaborators

C2N Diagnostics

Investigators

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Principal Investigator:	Adam Boxer, MD, PhD	UCSF Memory and Aging Center

More Information

Publications:

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.

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, Höglinger 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.

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. Review.

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.

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Responsible Party:	C2N Diagnostics
ClinicalTrials.gov Identifier:	NCT02494024
Other Study ID Numbers:	C2N-8E12-WW-104
First Posted:	July 10, 2015 Key Record Dates
Last Update Posted:	July 26, 2017
Last Verified:	July 2017

Keywords provided by C2N Diagnostics:


PSP C2N-8E12 tauopathy	Progressive Supranuclear Palsy Steele Richardson Olszewski Syndrome Humanized anti-tau antibody

Additional relevant MeSH terms:

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Paralysis Supranuclear Palsy, Progressive Neurologic Manifestations Nervous System Diseases Signs and Symptoms Basal Ganglia Diseases Brain Diseases Central Nervous System Diseases	Movement Disorders Ophthalmoplegia Ocular Motility Disorders Cranial Nerve Diseases Tauopathies Neurodegenerative Diseases Eye Diseases

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