Clinical Trials

Exclusion Criteria:

• Signed informed consent.
• Between 40 to 75 years old (inclusive).
• Have PSP diagnosed for less than 5 years with a current classification of probable PSP Richardson syndrome, a Progressive Supranuclear Palsy Rating scale (PSPRS, Golbe and Ohman-Strickland 2007) score < 40 and MOCA score > 17 at screening.
• Be able to ambulate independently or to take at least 5 steps with minimal assistance (Participant requires no more help than touching, providing at least 75% of total effort.  Participant is able to assume all of his body weight, but requires guidance for initiation, balance and/or stability) as performed at screening visit.
• At least a 12-month history of postural instability or falls within 3 years from disease onset as per medical history.
• Vertical supranuclear gaze palsy, or reduced velocity of vertical saccade at screening physical examination.
• Able and willing to meet all study requirements including:
  • Have a study partner who is reliable, competent, and at least 18 years of age, will be able to accompany the part.icipant to study visits, be knowledgeable of the participant's ongoing condition during the study to provide study related information to study site when required both in person and via a phone call;
  • Reside in a proximity to the study site to allow an unscheduled visit to happen timely (ideally less than 2 hours);
  • Able to undergo LP, CSF draws, and blood draws.
• If the participant is receiving levodopa/carbidopa, levodopa/benserazide, dopamine agonist, catechol-o-methyltransferase (COMT) inhibitor, rasagiline, CoQ10, or other Parkinson’s medications, acetylcholinesterase inhibitors, antipsychotics, memantine, or other non-tau modifying Alzheimer's medication, the doses must have been stable for at least 30 days prior to the screening visit and must remain stable for the duration of the study.  No such medication can be initiated during the study.

Exclusion Criteria:

• Live in a skilled nursing facility or dementia care facility.
• Evidence of motor neuron disease, or any other neurological disease that could explain symptoms.
• Any clinically significant laboratory abnormality, with the exception of these usually found in PSP patients; e.g., lower cholesterol, that may adversely and critically affect a patient's safety or protocol required clinical assessments in the study in the judgement of the investigator.
• Attempted suicide, suicidal ideation with a plan that required hospital admission within 12 months prior to Screening. For patients with (i) a suicide ideation score ≥ 4 on the Columbia Suicide Severity Rating Scale (C-SSRS) within the last 12 months, (ii) suicidal behaviors within the last 12 months (as measured by the answer “Yes” on any of the C-SSRS Suicidal Behavior Items), a risk assessment should be done by an appropriately-qualified mental health professional (e.g., a Psychiatrist or licensed Clinical Psychologist) to assess whether it is safe for the patient to participate in the study. In addition, patients deemed by the Investigator to be at significant risk of suicide, major depressive episode, psychosis, confusion state or violent behavior should be excluded.
• A clear and robust benefit from levodopa at the time of screening defined as improvement of the MDS-UPDRS motor scale by >30%.
• Use of lithium, methylene blue or other putative disease modifying drugs for PSP within 30 days of screening.
• Any previous use of experimental therapy within 30 days or 5 half-lives prior to Day 1, whichever is greater.
• History of hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical classes.
• Any condition that increases risk of meningitis unless patient is receiving appropriate prophylactic treatment.
• History of post-lumbar-puncture headache of moderate or severe intensity and/or blood patch.
• Hospitalization for any major medical or surgical procedure involving general anesthesia within 12 weeks of Screening or planned during the study.
• Have any other conditions which, in the opinion of the Investigator, would make the patient unsuitable for inclusion or could interfere with the patient participating in or completing the study.
• Patient is unable to undergo magnetic resonance imaging (MRI) due to for example claustrophobia or presents absolute contraindications to MRI (e.g., metallic implants, metallic foreign bodies, pacemaker, defibrillator).
• Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing of investigational drug and for 15 weeks after stopping study medication.
• Highly effective contraception methods include:
  • Total abstinence from heterosexual intercourse (when this is in line with the preferred and usual lifestyle of the participant). Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception;
  • Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks before taking investigational drug. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment;
  • Male sterilization (at least 6 months prior to screening);
  • For female participants on the study, the vasectomized male partner should be the sole partner for that participant;
  • Use of oral (estrogen and progesterone), injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS).  In case of use of oral contraception women should be stable on the same pill for a minimum of 3 months before taking study drug;
  • If local regulations deviate from the contraception methods listed above and require more extensive measures to prevent pregnancy, local regulations apply and will be described in the ICF;
  • Women are considered post-menopausal and not of childbearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks ago.  In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of childbearing potential;
  • Sexually active males, unless they always use condoms during intercourse while taking study drug and for 15 weeks (= 5 times the expected plasma terminal half-life of study medication. Plasma is considered to be the relevant compartment to provide indirect measurement of NIO752 in seminal fluid) after stopping study medication and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid.
• Patients with other significant brain MRI abnormalities by history or at screening.