NCT02494024

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).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
32

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Jul 2015

Geographic Reach
1 country

12 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 30, 2015

Completed
1 day until next milestone

Study Start

First participant enrolled

July 1, 2015

Completed
9 days until next milestone

First Posted

Study publicly available on registry

July 10, 2015

Completed
1.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2016

Completed
Last Updated

July 26, 2017

Status Verified

July 1, 2017

Enrollment Period

1.1 years

First QC Date

June 30, 2015

Last Update Submit

July 25, 2017

Conditions

Progressive Supranuclear Palsy

Keywords

PSPC2N-8E12tauopathyProgressive Supranuclear PalsySteele Richardson Olszewski SyndromeHumanized anti-tau antibody

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (3)

  • Immunogenicity as measured by the number of participants developing anti drug antibodies.

    up to 4 months

  • Area under the concentration vs time curve (AUC) of C2N-8E12

    up to 4 months

  • Elimination half-life of C2N-8E12

    up to 4 months

Study Arms (5)

Single dose C2N-8E12 level 1

EXPERIMENTAL

Single IV infusion of C2N-8E12

Drug: Single dose C2N-8E12

Single dose C2N-8E12 level 2

EXPERIMENTAL

Single IV infusion of C2N-8E12

Drug: Single dose C2N-8E12

Single dose C2N-8E12 level 3

EXPERIMENTAL

Single IV infusion of C2N-8E12

Drug: Single dose C2N-8E12

Single dose C2N-8E12 level 4

EXPERIMENTAL

Single IV infusion of C2N-8E12

Drug: Single dose C2N-8E12

Single dose placebo

PLACEBO COMPARATOR

Single IV infusion of placebo

Drug: Single dose placebo

Interventions

Single dose C2N-8E12DRUG

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

Single dose C2N-8E12 level 1Single dose C2N-8E12 level 2Single dose C2N-8E12 level 3Single dose C2N-8E12 level 4
Single dose placeboDRUG

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.

Single dose placebo

Eligibility Criteria

Age50 Years - 85 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (12)

University of Alabama

Birmingham, Alabama, 35294, United States

Location

Mayo Clinic

Scottsdale, Arizona, 85259, United States

Location

University of California, Los Angeles (UCLA)

Los Angeles, California, 90095, United States

Location

UCSD Department of Neurosciences

San Diego, California, 92037, United States

Location

University of California, San Francisco

San Francisco, California, 94158, United States

Location

University of Florida College of Medicine

Gainesville, Florida, 32607, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Indiana University Medical Center

Indianapolis, Indiana, 46202, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Columbia University

New York, New York, 10032-3795, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232-2551, United States

Location

Texas Health Presbyterian Dallas

Dallas, Texas, 75231, United States

Location

Related Publications (4)

  • 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.

    PMID: 24075978BACKGROUND

  • 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.

    PMID: 24873720BACKGROUND

  • 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.

    PMID: 8710059BACKGROUND

  • 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.

    PMID: 25815354BACKGROUND

MeSH Terms

Conditions

Supranuclear Palsy, ProgressiveTauopathies

Condition Hierarchy (Ancestors)

Basal Ganglia DiseasesBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesMovement DisordersOphthalmoplegiaOcular Motility DisordersCranial Nerve DiseasesNeurodegenerative DiseasesParalysisNeurologic ManifestationsEye DiseasesSigns and SymptomsPathological Conditions, Signs and Symptoms

Study Officials

  • Adam Boxer, MD, PhD

    UCSF Memory and Aging Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 30, 2015

First Posted

July 10, 2015

Study Start

July 1, 2015

Primary Completion

August 1, 2016

Study Completion

August 1, 2016

Last Updated

July 26, 2017

Record last verified: 2017-07

Locations

US(12)