Multiple Ascending Dose Study of Intravenously Administered BMS-986168 (BIIB092) in Patients With Progressive Supranuclear Palsy

This study, previously posted by Bristol-Myers Squibb, has transitioned to Biogen under a
licensing agreement.

Inclusion Criteria

1. Probable or possible PSP defined as:

- at least a 12-month history of postural instability or falls during the first 3
years that symptoms are present

- a decreased downward saccade velocity at screening defined as observable eye
movement deviation from the "main sequence" linear relationship between saccade
amplitude and saccade velocity; or supranuclear ophthalmoplegia defined as 50%
reduction in upward gaze or 30% reduction in downward gaze; and

- 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; and

- an akinetic-rigid syndrome with prominent axial rigidity.

- presence of symptoms for less than 5 years.

2. Body weight range of ≥ 43 kg/95 lbs to ≤ 118 kg/260 lbs.

3. Able to tolerate MRI.

4. Able to perform all protocol-specified assessments and comply with the study visit
schedule.

5. Have reliable caregiver to accompany 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 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.

6. Score ≥ 20 on the Mini Mental State Exam (MMSE) at screening.

7. Patient must reside outside a skilled nursing facility or dementia care facility at
the time of screening, and admission to such a facility is not planned. Residence in
an assisted living facility is allowed.

8. Ability to ambulate independently or with assistance defined as the ability to take at
least 5 steps with a walker (guarding is allowed provided there is no contact) or the
ability to take at least 5 steps without a walker or cane with the assistance of
another person who can only have contact with one upper extremity.

9. Stable on other chronic medications for at least 30 days prior to screening.

10. Women of child bearing potential (WOCBP) and sexually active fertile men with partners
who are WOCBP must use highly effective birth control.

Exclusion Criteria

1. Presence of other significant neurological or psychiatric disorders.

2. History of or screening brain MRI scan indicative of significant abnormality.

3. History of cancer within 5 years of screening with the exception of fully excised
non-melanoma skin cancers or non-metastatic prostate cancer that has been stable for
at least 6 months.

4. History of clinically significant hematological, endocrine, cardiovascular, renal,
hepatic, gastrointestinal, or neurological disease.

5. Inability to be venipunctured and/or tolerate venous access.

6. Contraindication to undergoing an LP.

7. Recent drug or alcohol abuse as defined in DSM IV.

8. Treatment with any investigational drugs (including placebo) or devices within 90 days
prior to screening.

9. Contraindication to the MRI examination for any reason

10. 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.

11. History of allergy, hypersensitivity, or serious adverse reaction to monoclonal
antibodies or related compounds or allergy to any of the components of the study drug