Clinical trial NCT02494024: Safety, Tolerability, and Pharmacokinetics of C2N-8E12 in Subjects With Progressive Supranuclear Palsy
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Progressive Supranuclear Palsy
Keywords: PSP
C2N-8E12
tauopathy
Progressive Supranuclear Palsy
Steele Richardson Olszewski Syndrome
Humanized anti-tau antibody
Lead sponsor: C2N Diagnostics
Sponsor class: INDUSTRY
First posted: 2015-07-10
Enrollment: 32
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Eligibility 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.

Primary outcomes:
measure: 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.
timeFrame: up to 4 months
Secondary outcomes:
measure: Immunogenicity as measured by the number of participants developing anti drug antibodies.
timeFrame: up to 4 months
measure: Area under the concentration vs time curve (AUC) of C2N-8E12
timeFrame: up to 4 months
measure: Elimination half-life of C2N-8E12
timeFrame: up to 4 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: Los Angeles
country: United States
facility: University of California, Los Angeles (UCLA)
state: California
city: San Diego
country: United States
facility: UCSD Department of Neurosciences
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Gainesville
country: United States
facility: University of Florida College of Medicine
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Indianapolis
country: United States
facility: Indiana University Medical Center
state: Indiana
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: Columbia University
state: New York
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Texas Health Presbyterian Dallas
state: Texas
Study officials:
affiliation: UCSF Memory and Aging Center
name: Adam Boxer, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.
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. doi: 10.1212/wnl.47.1.1.
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.