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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Progressive Supranuclear Palsy

Intervention / Treatment
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* Drug: Single dose C2N-8E12
* Drug: Single dose placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single dose C2N-8E12 level 1<br>Single IV infusion of C2N-8E12 | Drug: Single dose C2N-8E12<br>* C2N-8E12 is a humanized recombinant anti-human tau antibody.<br>|
| Experimental: Single dose C2N-8E12 level 2<br>Single IV infusion of C2N-8E12 | Drug: Single dose C2N-8E12<br>* C2N-8E12 is a humanized recombinant anti-human tau antibody.<br>|
| Experimental: Single dose C2N-8E12 level 3<br>Single IV infusion of C2N-8E12 | Drug: Single dose C2N-8E12<br>* C2N-8E12 is a humanized recombinant anti-human tau antibody.<br>|
| Experimental: Single dose C2N-8E12 level 4<br>Single IV infusion of C2N-8E12 | Drug: Single dose C2N-8E12<br>* C2N-8E12 is a humanized recombinant anti-human tau antibody.<br>|
| Placebo Comparator: Single dose placebo<br>Single IV infusion of placebo | Drug: Single dose placebo<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PSP, C2N-8E12, tauopathy, Progressive Supranuclear Palsy, Steele Richardson Olszewski Syndrome, Humanized anti-tau antibody