Young Plasma Transfusions for Progressive Supranuclear Palsy

August 7, 2020 updated by: University of California, San Francisco

A 6 Month, Open-Label, Pilot Futility Clinical Trial of Monthly Young Healthy Male Donor Plasma Transfusions for Progressive Supranuclear Palsy

This is a phase 1, multi-center, open-label study of the safety, tolerability, pharmacodynamics, and preliminary efficacy of young (<30 years of age) healthy male donor plasma transfusions in patients with PSP. Up to 10 subjects will receive once monthly 4-unit transfusions of young healthy male donor plasma for 6 months.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a phase 1, multi-center, open-label study of the safety, tolerability, pharmacodynamics, and preliminary efficacy of young (<30 years of age) healthy male donor plasma transfusions in patients with PSP. Up to 10 subjects will receive once monthly 4-unit transfusions of young healthy male donor plasma for 6 months.

If ≥3 subjects experience drug limiting toxicity (DLT), as defined in Section 7.19, the study will be terminated. Any subject that experiences a DLT will be discontinued from further treatment with the study drug.

An interim futility analysis will be performed after five subjects have completed 6 months of study drug treatment. If the criteria listed in Section 9.3 of this protocol are met, an additional 5 subjects will be enrolled in the trial. If not, the trial will be terminated.

Study Type

Interventional

Enrollment (Actual)

6

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94158
        • University of California, San Francisco, Memory and Aging Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years to 85 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Meets National Institute of Neurological Disorders and Stroke - Society for Progressive Supranuclear Palsy (NINDS-SPSP) probable or possible PSP criteria (Litvan et al. 1996b), as modified for the AL-108-231 davunetide trial (Boxer et al. 2014);
  2. Between 50 and 85 years of age (inclusive);
  3. MRI at Screening is consistent with PSP (≤ 4 microhemorrhages and no large strokes or severe white matter disease);
  4. MMSE score at Screening is between 14 and 30 (inclusive);
  5. Stable medications for 2 months prior to Screening, including Food and Drug Administration- (FDA-) approved Alzheimer's disease (AD) medications and Parkinson's disease medications;
  6. Availability of a study partner who knows the subject well and is willing to accompany the subject to all trial visits and to participate in questionnaires;
  7. Agrees to 3 MRIs;
  8. Agrees to 2 lumbar punctures for CSF examination;
  9. Signed and dated written informed consent obtained from the subject and subject's caregiver in accordance with local IRB regulations;

  10. Males and all WCBP agree to abstain from sex or use an adequate method of contraception for the duration of the study and for 30 days after the last dose of study drug.

    • Adequate contraceptive methods include those with a low failure rate, i.e., less than 1% per year, when used consistently and correctly, such as complete abstinence from sexual intercourse with a potentially fertile partner, and some double barrier methods (condom with spermicide) in conjunction with use by the partner of an intrauterine device (IUD), diaphragm with spermicide, oral contraceptives, birth control patch or vaginal ring, oral, or injectable or implanted contraceptives;
    • For this study, a woman who has been surgically sterilized or who has been in a state of amenorrhea for more than two years will be deemed not to be of childbearing potential.

Exclusion Criteria:

  1. Meets National Institute on Aging-Alzheimer's Association Workgroups criteria for probable AD (McKhann et al. 2011);
  2. Any medical condition other than PSP that could account for cognitive deficits (e.g., active seizure disorder, stroke, vascular dementia);
  3. A prominent and sustained response to levodopa therapy;
  4. History of significant cardiovascular, hematologic, renal, or hepatic disease (or laboratory evidence thereof);
  5. History of major psychiatric illness or untreated depression;
  6. Neutrophil count <1,500/mm3, platelets <100,000/mm3, serum creatinine >1.5 x upper limit of normal (ULN), total bilirubin >1.5 x ULN, alanine aminotransferase (ALT) >3 x ULN, aspartate aminotransferase (AST) >3 x ULN, or INR >1.2 at Screening evaluations;
  7. Evidence of any clinically significant findings on Screening or baseline evaluations which, in the opinion of the Investigator would pose a safety risk or interfere with appropriate interpretation of study data;
  8. Current or recent history (within four weeks prior to Screening) of a clinically significant bacterial, fungal, or mycobacterial infection;
  9. Current clinically significant viral infection;
  10. Major surgery within four weeks prior to Screening;
  11. Any contraindication to or unable to tolerate lumbar puncture at Screening, including use of anti-coagulant medications such as warfarin. Daily administration of 81 mg aspirin will be allowed as long as the dose is stable for 30 days prior to Screening;
  12. Any contraindication to monthly plasma transfusions, including but not limited to: a. History of significant transfusion complications; b. Lack of a competent adult in the home to summon medical assistance if needed; c. Lack of a telephone to contact emergency personnel or lack of easy access for emergency vehicles; d. Compatible plasma units not available; e. Prior intolerance to intravenous (IV) fluids; f. IgA deficiency by history or laboratory evidence at Screening; g. Uremia or bleeding; h. Any concurrent use of an anti-coagulant therapy. Daily administration of 81 mg aspirin will be allowed as long as the dose is stable for 30 days prior to Screening. Anti-platelet drugs are acceptable.
  13. Treatment with another investigational drug or participation in another interventional clinical trial within 3 months of Screening;
  14. Treatment with any human blood product, including IV immunoglobulin, during the 6 months prior to Screening or during the trial;
  15. Pregnant or lactating;
  16. Positive pregnancy test at Screening or Baseline (Day 1);
  17. Cancer within 5 years of Screening, except for non-metastatic skin cancer or non-metastatic prostate cancer not expected to cause significant morbidity or mortality within one year of Baseline.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Fresh Frozen Plasma
Fresh Frozen Plasma [young (<30 years of age) healthy male donors]
Biological: Fresh Frozen Plasma
Fresh Frozen Plasma [young (<30 years of age) healthy male donors] Solution for intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients experiencing drug limiting toxicity (DLT)
Time Frame: 6 months
To determine the safety and tolerability of once monthly 4-unit transfusions of young (<30 years of age) healthy male donor plasma for 6 months in patients with progressive supranuclear palsy (PSP). Number of patients experiencing drug limiting toxicity (DLT), defined as: 1) any Grade 3 or higher adverse event (AE) per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) for which there is reasonable possibility that salsalate caused the event, 2) any Grade 2 AE in the CTCAE system organ class of nervous system disorders that is considered clinically significant and for which there is reasonable possibility that salsalate caused the event, or 3) any Grade 2 or higher treatment-related adverse events during administration that do not resolve promptly with supportive treatment
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in motor function as measured by Progressive Supranuclear Palsy Rating Scale (PSPRS)
Time Frame: 6 months
Motor function as measured by Progressive Supranuclear Palsy Rating Scale (PSPRS) comprising 28 items in six categories: daily activities (by history), behavior, bulbar, ocular motor, limb motor and gait/midline The available total score ranges from 0 to 100; lower scores reflect better outcome.
6 months
Changes in cognition as measured by Progressive Supranuclear Palsy Rating Scale (PSPRS)
Time Frame: 6 months
Cognitive function as measured by Progressive Supranuclear Palsy Rating Scale (PSPRS) comprising 28 items in six categories: daily activities (by history), behavior, bulbar, ocular motor, limb motor and gait/midline The available total score ranges from 0 to 100; lower scores reflect better outcome.
6 months
Changes in activities of daily living as measured by Progressive Supranuclear Palsy Rating Scale (PSPRS)
Time Frame: 6 months
Activities of daily living as measured by Progressive Supranuclear Palsy Rating Scale (PSPRS) comprising 28 items in six categories: daily activities (by history), behavior, bulbar, ocular motor, limb motor and gait/midline The available total score ranges from 0 to 100; lower scores reflect better outcome.
6 months
Changes in behavior as measured by Progressive Supranuclear Palsy Rating Scale (PSPRS)
Time Frame: 6 months
Behavior as measured by Progressive Supranuclear Palsy Rating Scale (PSPRS) comprising 28 items in six categories: daily activities (by history), behavior, bulbar, ocular motor, limb motor and gait/midline The available total score ranges from 0 to 100; lower scores reflect better outcome.
6 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in brain volume
Time Frame: 6 months
Changes in brain volume [T1-weighted volumetric magnetic resonance imaging (vMRI)], brain network functional and structural connectivity and perfusion [resting state functional magnetic resonance imaging (rsfMRI), diffusion tensor imaging (DTI), and arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI)]
6 months
Changes in concentration of cerebrospinal fluid (CSF) biomarkers
Time Frame: 6 months
Changes in the concentrations of cerebrospinal fluid (CSF) biomarkers of neurodegeneration [neurofilament light chain (NfL), total tau, and phosphorylated tau]
6 months
Changes in motor function
Time Frame: 6 months
Motor function as measured by Schwab and England Activities of Daily Living scale (SEADL), PSP-Quality of Life. Scores range from one hundred percent, which indicates a completely independent individual, and zero percent, which indicates an individual in who is no longer functioning.
6 months
Changes in cognition
Time Frame: 6 months
Cognition as measured by Schwab and England Activities of Daily Living scale (SEADL), PSP-Quality of Life. Scores range from one hundred percent, which indicates a completely independent individual, and zero percent, which indicates an individual in who is no longer functioning.
6 months
Changes in activities of daily living
Time Frame: 6 months
Activities of daily living as measured by Schwab and England Activities of Daily Living scale (SEADL), PSP-Quality of Life. Scores range from one hundred percent, which indicates a completely independent individual, and zero percent, which indicates an individual in who is no longer functioning.
6 months
Changes in behavior
Time Frame: 6 months
Behavior as measured by Schwab and England Activities of Daily Living scale (SEADL), PSP-Quality of Life. Scores range from one hundred percent, which indicates a completely independent individual, and zero percent, which indicates an individual in who is no longer functioning.
6 months
Changes in saccade eye movements
Time Frame: 6 months
To explore the effects of 2,250 mg daily salsalate on changes in saccade latency, velocity, and amplitude [infrared oculometry] from Screening to end of month 3 and end of month 6 compared to historical data
6 months
Changes in sleep
Time Frame: 6 months
Changes in actigraphic measures
6 months
Changes in activity levels
Time Frame: 6 months
Changes in actigraphic measures
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Francisco

Investigators

  • Principal Investigator: Richard Tsai, MD, MBA, University of California, San Francisco Memory and Aging Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2015

Primary Completion (Actual)

December 1, 2017

Study Completion (Actual)

December 1, 2019

Study Registration Dates

First Submitted

May 19, 2015

First Submitted That Met QC Criteria

June 1, 2015

First Posted (Estimate)

June 2, 2015

Study Record Updates

Last Update Posted (Actual)

August 11, 2020

Last Update Submitted That Met QC Criteria

August 7, 2020

Last Verified

August 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PSP-YP-001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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