Clinical Trials

Inclusion Criteria:

• Probable PSP defined as meeting all 4 of the following:
  • At least a 12-month history of postural instability during the first 3 years that symptoms are present,OR at least a 12-month history of falls during the first 3 years that symptoms are present;
  • Vertical supranuclear gaze palsy defined as clear limitation of the range of voluntary gaze in the vertical more than in the horizontal plane (more than expected with age), which is overcome by activation of the vestibulo-ocular reflex (at later stages, the vestibulo-ocular reflex may be lost, or the maneuver prevented by nuchal rigidity), OR slow velocity of vertical saccades (i.e., decreased velocity (and gain) of vertical greater than horizontal saccadic eye movements).
    • Note: Gaze should be assessed by command to a stationary target rather than by pursuit, with the target >20 ° from the position of primary gaze. Typically, saccadic movement is slow enough for the examiner to see its progress, rather than just its initial and final positions. Deficits are more prominent in the vertical than the horizontal plane. A delay in initiation of saccades is not considered slowing.
  • Age at symptom onset of 40 to 85 years by history and current age between 41 and 86 years, inclusive, at the time of Screening;
  • Akinetic-rigid syndrome with prominent axial rigidity.
• Presence of PSP symptoms for less than 5 years.
• Body weight range of ≥ 41 kg (90 lbs) to ≤ 118 kg (260 lbs).
• Able to perform all protocol-specified assessments, including neuropsychological tests; and comply with taking study medication and the study visit schedule, as judged by the investigator.
• Has a reliable caregiver to accompany the patient to all study visits. Caregiver must be able to read, understand, and speak local language fluently to ensure comprehension of informed consent and informant-based assessments of the patient. Caregiver must also have frequent contact with patient (at least 3 hours per week at one time or at different times) and be willing to monitor the patient's health and concomitant medications throughout the study.
• Score ≥ 18 on the Mini Mental State Exam (MMSE) at Screening.
• Patient must reside outside a skilled nursing facility or dementia care facility at the time of Screening, and admission to such a facility must not be planned. Residence in an assisted living facility is allowed.
• If patient is receiving coenzyme Q10, levodopa/carbidopa, levodopa/ benserazide, a dopamine agonist, catechol-o-methyltransferase inhibitor, other Parkinson's disease medication, or memantine with or without acetylcholinesterase inhibitors for cognition; the dose must have been stable for at least 30 days prior to Screening and must remain stable for the duration of the study. No such medication may be initiated during the study.
• Stable on other chronic medications for at least 30 days prior to Screening.
• If female, must be postmenopausal (for at least 2 years), surgically sterilized (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy), or agree to use highly effective methods of contraception from Screening through Week 52.
• If male, with a partner who is not postmenopausal (for at least 2 years) or surgically sterilized (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy), the patient must agree that he and his partner will use highly effective methods of contraception from Screening through Week 52.

Exclusion Criteria:

• Presence of other significant neurological or psychiatric disorders including (but not limited to) Alzheimer's disease; dementia with Lewy bodies; prion disease; Parkinson's disease (which has not subsequently been revised to PSP); amyotrophic lateral sclerosis or other motor neuron disease; multiple sclerosis; any psychotic disorder; severe bipolar or unipolar depression; prior history of a suicide attempt or current suicidal thoughts or behavior that are believed to represent a safety risk as indicated by a “yes” response to Question 2 on the C-SSRS; seizure; brain tumor or other space-occupying lesion; history of stroke; or history of severe head injury within the past 20 years.
• History of significant brain abnormality, including, but not limited to, prior hemorrhage or infarct, cerebral contusion, encephalomalacia, aneurysm, vascular malformation, subdural hematoma (SDH), hydrocephalus, space-occupying lesion (e.g., abscess or brain tumor such as meningioma). If there is history or evidence on neurologic exam suggesting possible SDH, patients should be fully evaluated, including magnetic resonance imaging (MRI) if indicated, to exclude significant, new SDH.
• Presence of cerebellar ataxia, choreoathetosis, early symptomatic autonomic dysfunction, or tremor while at rest.
• Known history of serum or plasma progranulin level less than one standard deviation below the normal patient mean for the laboratory performing the assay.
• Known presence of disease-associated mutation in TARDBP, GRN, CHMPB2, or VCP genes; or any other frontotemporal lobar degeneration causative genes not associated with underlying tau pathology.
• History of deep brain stimulator surgery other than sham surgery for deep brain stimulation clinical trial.
• History of early, prominent rapid eye movement sleep behavior disorder.
• History of cancer within 5 years of Screening, with the exception of fully excised non-melanoma skin cancers.
• History of clinically significant hematological, endocrine, cardiovascular, renal, hepatic, or gastrointestinal disease.
• Uncontrolled hypertension, defined as confirmed systolic blood pressure (SBP) > 170 mmHg and/or diastolic blood pressure (DBP) > 100 mmHg at Screening.
• Hypotension, defined as confirmed SBP < 90 mmHg and/or DBP < 60 mmHg at Screening.
• Any major surgery within 4 weeks of Screening.
• Receipt of an investigational immunomodulator or monoclonal antibody within 180 days (or 5 half-lives, whichever is longer) prior to Screening.
• Receipt of systemic corticosteroids within 30 days prior to Screening.
• Autoimmune disease (quiescent rheumatoid arthritis, psoriasis, or controlled Type 1 diabetes are acceptable).
• Donation of blood or serum > 500 mL to a blood bank or in a clinical study (except a Screening Visit) within 3 months of Screening.
• Blood transfusion within 4 weeks of Screening.
• Inability to be venipunctured and/or tolerate venous access.
• Contraindication to undergoing a lumbar puncture (LP) including, but not limited to: inability to tolerate an appropriately flexed position for the time necessary to perform an LP; international normalized ratio (INR) > 1.4 or other coagulopathy; platelet count of < 120,000/μL; infection at the desired LP site; taking anti-coagulant medication within 30 days of Screening (Note: aspirin is permitted); severe degenerative arthritis of the lumbar spine; suspected non-communicating hydrocephalus or intracranial mass; prior history of spinal mass or trauma; symptoms or signs of elevated intracranial pressure, e.g., symptoms or history of head injury or abnormal funduscopic exam.
• Has smoked or used tobacco products within 6 months prior to study drug administration.
• Within 4 weeks of Screening (first visit), concurrent treatment with antipsychotic agents or mood stabilizers (e.g., valproate, lithium) or benzodiazepines, with the following exceptions:
  • Patients who take short-acting benzodiazepines (only temazepam or zolpidem are allowed) for sleep may continue to do so if they have been on a stable dose for 30 days prior to Screening;
  • Clonazepam may be used for treatment of restless legs syndrome, dystonia, or painful rigidity associated with PSP, if the dose has been stable for 30 days prior to Screening and is not expected to change during the study;
  • Quetiapine or clozapine may be permitted if at a stable dose for at least 30 days prior to Screening.
• Recent (within 6 months of study drug administration) drug or alcohol abuse as defined in the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, Diagnostic Criteria for Drug and Alcohol Abuse.
• Treatment with any investigational drug (including placebo) or device within 30 days prior to Screening.
• Any vaccination within 30 days prior to study drug administration.
• History of a clinically significant medical condition that would interfere with the patient’s ability to comply with study instructions, would place the patient at increased risk, or might confound the interpretation of the study results.
• Known history of human immunodeficiency virus.
• Physical and laboratory test findings, including the following:
  • Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG, or clinical laboratory determinations beyond what is consistent with the target population;
  • Clinically significant abnormality on 12-lead ECG prior to study drug administration, confirmed by repeat testing;
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1.5 × upper limit of normal (ULN), confirmed by repeat testing;
  • Total bilirubin > 1.2 × ULN (unless due to Gilbert’s syndrome);
  • Serum creatinine > 168 μmol/L (1.9 mg/dL), confirmed by repeat testing;
  • Hematocrit < 35% for males and < 32% for females or absolute neutrophil cell count of < 1500/μL;
  • Clinically significant abnormal thyroid stimulating hormone (TSH) test;
  • Abnormally increased number of white blood cells (> 7 cells/mm3) in the CSF obtained at the Screening Visit; if there is evidence that the spinal tap was traumatic, patients with > 7 cells/mm^3 must be discussed with the medical monitor to determine if they may be eligible;
  • Hemoglobin A1C > 7%, confirmed by repeat testing;
  • Positive blood screen for human immunodeficiency virus (HIV), hepatitis C antibody, or hepatitis B surface antigen.
• Allergy to any of the components of TPN-101.
• History of any significant drug allergy (such as anaphylaxis or hepatotoxicity).