Multiple Ascending Dose Study of Intravenously Administered BMS-986168 (BIIB092) in Patients With Progressive Supranuclear Palsy (CN002-003)

Biogen

Status and phase: Completed; Phase 1

Conditions: Progressive Supranuclear Palsy

Treatments: Drug: BIIB092; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02460094

CN002-003

Details and patient eligibility

About

The purpose of this study is to evaluate the safety and tolerability of multiple ascending intravenous infusions of BMS-986168 and to assess the pharmacokinetics and immunogenicity of BIIB092, and pharmacodynamics of BIIB092 on cerebrospinal fluid (CSF) extracellular tau (eTau) concentrations in participants with Progressive Supranuclear Palsy.

Full description

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

Enrollment: 48 patients

Sex: All

Ages: 41 to 86 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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48 participants in 4 patient groups

Panel 1: BIIB092/ Placebo

Experimental group

Description:

BIIB092 or matching placebo administered by intravenous (IV) injection, up to a maximum of 3 doses once every four weeks.

Treatment:

Drug: Placebo

Drug: BIIB092

Panel 2: BIIB092/ Placebo

Experimental group

Description:

BIIB092 or matching placebo administered by intravenous (IV) injection, up to a maximum of 3 doses once every four weeks.

Treatment:

Drug: Placebo

Drug: BIIB092

Panel 3: BIIB092/ Placebo

Experimental group

Description:

BIIB092 or matching placebo administered by intravenous (IV) injection, up to a maximum of 3 doses once every four weeks.

Treatment:

Drug: Placebo

Drug: BIIB092

Panel 4: BIIB092/ Placebo

Experimental group

Description:

BIIB092 or matching placebo administered by intravenous (IV) injection, up to a maximum of 3 doses once every four weeks.

Treatment:

Drug: Placebo

Drug: BIIB092