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

Primary Purpose

Progressive Supranuclear Palsy

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Single dose C2N-8E12
Single dose placebo
Sponsored by
C2N Diagnostics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Progressive Supranuclear Palsy focused on measuring PSP, C2N-8E12, tauopathy, Progressive Supranuclear Palsy, Steele Richardson Olszewski Syndrome, Humanized anti-tau antibody

Eligibility Criteria

50 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Alabama
  • Mayo Clinic
  • University of California, Los Angeles (UCLA)
  • UCSD Department of Neurosciences
  • University of California, San Francisco
  • University of Florida College of Medicine
  • Mayo Clinic
  • Indiana University Medical Center
  • Mayo Clinic
  • Columbia University
  • Vanderbilt University Medical Center
  • Texas Health Presbyterian Dallas

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

Single dose C2N-8E12 level 1

Single dose C2N-8E12 level 2

Single dose C2N-8E12 level 3

Single dose C2N-8E12 level 4

Single dose placebo

Arm Description

Single IV infusion of C2N-8E12

Single IV infusion of C2N-8E12

Single IV infusion of C2N-8E12

Single IV infusion of C2N-8E12

Single IV infusion of placebo

Outcomes

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.

Secondary Outcome Measures

Immunogenicity as measured by the number of participants developing anti drug antibodies.
Area under the concentration vs time curve (AUC) of C2N-8E12
Elimination half-life of C2N-8E12

Full Information

First Posted
June 30, 2015
Last Updated
July 25, 2017
Sponsor
C2N Diagnostics
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1. Study Identification

Unique Protocol Identification Number
NCT02494024
Brief Title
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

2. Study Status

Record Verification Date
July 2017
Overall Recruitment Status
Completed
Study Start Date
July 2015 (undefined)
Primary Completion Date
August 2016 (Actual)
Study Completion Date
August 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
C2N Diagnostics

4. Oversight

Data Monitoring Committee
Yes

5. 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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Progressive Supranuclear Palsy
Keywords
PSP, C2N-8E12, tauopathy, Progressive Supranuclear Palsy, Steele Richardson Olszewski Syndrome, Humanized anti-tau antibody

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
32 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Single dose C2N-8E12 level 1
Arm Type
Experimental
Arm Description
Single IV infusion of C2N-8E12
Arm Title
Single dose C2N-8E12 level 2
Arm Type
Experimental
Arm Description
Single IV infusion of C2N-8E12
Arm Title
Single dose C2N-8E12 level 3
Arm Type
Experimental
Arm Description
Single IV infusion of C2N-8E12
Arm Title
Single dose C2N-8E12 level 4
Arm Type
Experimental
Arm Description
Single IV infusion of C2N-8E12
Arm Title
Single dose placebo
Arm Type
Placebo Comparator
Arm Description
Single IV infusion of placebo
Intervention Type
Drug
Intervention Name(s)
Single dose C2N-8E12
Intervention Description
C2N-8E12 is a humanized recombinant anti-human tau antibody.
Intervention Type
Drug
Intervention Name(s)
Single dose placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
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 Measure Information:
Title
Immunogenicity as measured by the number of participants developing anti drug antibodies.
Time Frame
up to 4 months
Title
Area under the concentration vs time curve (AUC) of C2N-8E12
Time Frame
up to 4 months
Title
Elimination half-life of C2N-8E12
Time Frame
up to 4 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Adam Boxer, MD, PhD
Organizational Affiliation
UCSF Memory and Aging Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Mayo Clinic
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Facility Name
University of California, Los Angeles (UCLA)
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
UCSD Department of Neurosciences
City
San Diego
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Facility Name
University of Florida College of Medicine
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32607
Country
United States
Facility Name
Mayo Clinic
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
Indiana University Medical Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Columbia University
City
New York
State/Province
New York
ZIP/Postal Code
10032-3795
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232-2551
Country
United States
Facility Name
Texas Health Presbyterian Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
24075978
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.
Results Reference
background
PubMed Identifier
24873720
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.
Results Reference
background
PubMed Identifier
8710059
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.
Results Reference
background
PubMed Identifier
25815354
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.
Results Reference
background

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

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