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

Progressive Supranuclear Palsy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02494024
• Other study ID #: C2N-8E12-WW-104
• Status: Completed
• Phase: Phase 1
• First received: June 30, 2015
• Last updated: July 25, 2017
• Start date: July 2015
• Est. completion date: August 2016

Study information

• Verified date: July 2017
• Source: C2N Diagnostics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: August 2016
• Est. primary completion date: August 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Paralysis
• Progressive Supranuclear Palsy
• Supranuclear Palsy, Progressive

Intervention

Drug:
• Single dose C2N-8E12
C2N-8E12 is a humanized recombinant anti-human tau antibody.
• 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.

Locations

Country	Name	City	State
United States	University of Alabama	Birmingham	Alabama
United States	Texas Health Presbyterian Dallas	Dallas	Texas
United States	University of Florida College of Medicine	Gainesville	Florida
United States	Indiana University Medical Center	Indianapolis	Indiana
United States	Mayo Clinic	Jacksonville	Florida
United States	University of California, Los Angeles (UCLA)	Los Angeles	California
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Columbia University	New York	New York
United States	Mayo Clinic	Rochester	Minnesota
United States	UCSD Department of Neurosciences	San Diego	California
United States	University of California, San Francisco	San Francisco	California
United States	Mayo Clinic	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
C2N Diagnostics

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		up to 4 months
Secondary	Immunogenicity as measured by the number of participants developing anti drug antibodies.		up to 4 months
Secondary	Area under the concentration vs time curve (AUC) of C2N-8E12		up to 4 months
Secondary	Elimination half-life of C2N-8E12		up to 4 months