A Multicenter, Open-Label, Long-Term Treatment Study of Intravenously Administered BMS-986168 in Patients with Progressive Supranuclear Palsy Who Participated in Study CN002003
- CTRC Inpatient
- CTRC Outpatient
- UT Southwestern Ambulatory Services
- UT Southwestern-Other
Padraig O'Suilleabhain, M.D.
This is an open-label, multiple-dose, safety, tolerability, PK, PD, and immunogenicity study of BMS-986168 administered by iV infusion in patients with PSP who have previously received BMS-986168 or placebo in Study Cn002003.
Patients who complete the double-blind, MaD study, Cn002003, and meet the entry criteria for Cn002004 will have the option to enter this open-label extension study. Patients may be enrolled in Cn002004 at the time they complete Cn002003. Therefore, the Day 85 visit of Cn002003
will be the Day 1 visit for the current study. if there is a delay between Cn002003 completion and enrollment into Cn002004, Cn002004 Day 1 procedures can be completed at a separate visit. it is anticipated that no more than 2 weeks will elapse between completing Cn002003 and
enrollment into Cn002004.
Study visits will be conducted every 4 weeks. Study drug will be administered and safety, PK, PD, and exploratory assessments will be performed . The study will generally be conducted on an outpatient basis unless some procedures would be better performed on an inpatient basis based on the needs of the patient. Patients should be observed and monitored by study personnel for approximately 2 hours after the end of an infusion. Patients
with ongoing aes or serious aes (Saes) will remain at the site or be sent to an inpatient monitoring facility until the investigator has determined that these events have resolved or do not require inpatient monitoring. after Week 24, except for those visits when clinical scales, lumbar
punctures (LPs), MRis, or eye tracking assessments are performed, visits and procedures may be performed in the home as long as appropriate services are available to perform the required study procedures and adequately monitor for potential safety events; however, in the event that the
patient experienced an infusion reaction during the first 24 weeks of the protocol, the patient should not be administered BMS-986168 in the home unless previously approved by the study medical monitor.
up to approximately 48 patients will be enrolled and treated in 4 panels. The first 3 dose panels will each include up to approximately 8 patients and the fourth panel will include up to approximately 24 patients. additional patients may have been added to some dose panels in Cn002003 (up to a maximum of 4 additional patients per panel) based on PK/PD considerations.
The date the first patient signs a study-specific iCF will be defined as the start of the study. a patient is considered enrolled when the study-specific informed consent is signed. The date that the last patient completes the last study visit will be defined as the end of the study. Patients who withdraw from the study will be requested to complete early termination procedures.
Physical and neurological examinations, vital sign measurements, 12-lead eCGs, and clinical laboratory evaluations will be performed at selected times throughout the treatment period. Patients will be closely monitored for aes (including injection site reactions) throughout the
study. Blood will be collected for PK and PD analysis at the times. approximately 159 mL of blood will be drawn from each patient during the first
84 weeks of this study.
an LP will be performed for collection of CSF to evaluate BMS-986168 concentrations, free eTau, and other exploratory markers. it is anticipated that each patient will have total of 2 LPs over the course of the study, including the LP that occurs on Day 1 (Day 84 of Cn002003) and a
second LP at Week 48.
Progressive supranuclear palsy symptoms will be assessed using clinical assessments (PSPRS, SeaDL scale, CGi-S, CGi-C, euroQol, and MoCa) and neuropsychological testing (RBanS, phonemic fluency, letter-number sequencing, and color trail test), and patients will also complete
1. Signed Written Informed Consent
a) Signed written informed consent must be obtained from the patients in accordance with
requirements of the study center[Single Quote]s IRB or IEC prior to the initiation of any
2. Target Population
a) Completed treatment in Study CN002003.
b) A diagnosis of probable or possible PSP consistent with Study CN002003 criteria with no
new medical information or diagnoses since enrollment into Study CN002003 that might
confer doubt on the PSP diagnosis.
c) Able to tolerate MRI.
d) Able to perform all protocol-specified assessments and comply with the study visit
e) 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[Single Quote]s health and concomitant medications throughout the study.
f) Patient must reside outside a skilled nursing facility or dementia care facility at the time
of enrollment, and admission to such a facility is not planned. Residence in an assisted
living facility is allowed.
3. Age and Reproductive Status
a) Males and females, ages 41 to 86 years, inclusive (at screening of CN002003).
b) Women of childbearing potential (WOCBP) must have a negative serum or urine
pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic
gonadotropin) within 24 hours prior to the start of study drug.
c) Women must not be breastfeeding.
d) Women of childbearing potential must agree to follow instructions for method(s) of
contraception for the duration of treatment with BMS-986168 plus 5 half-lives of
BMS-986168 (110 days) plus 30 days (duration of ovulatory cycle) for a total of
140 days post-treatment completion.
e) Males who are sexually active with WOCBP must agree to follow instructions for
method(s) of contraception for the duration of treatment with BMS-986168 plus
5 half-lives of the study drug (110 days) plus 90 days (duration of sperm turnover) for a
total of 200 days post-treatment completion.
f) Azoospermic males and WOCBP who are continuously not heterosexually active are
exempt from contraceptive requirements. However, WOCBP must still undergo
pregnancy testing as described in this section.