Efficacy, Safety and Tolerability of BAF312 Compared to Placebo in Patients With Intracerebral Hemorrhage (ICH).

NCT03338998 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: CBAF312X2207
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 11

Brief Summary

This is a randomized, placebo-controlled, subject and investigator-blinded study to evaluate efficacy, safety and tolerability of BAF312 in participants with intracerebral hemorrhage (ICH)

Conditions

Hemorrhagic Stroke; Intracerebral Hemorrhage (ICH)

Keywords

stroke; intracerebral hemorrhage; ICH; BAF312; siponimod; sphingosine-1-phosphate receptor; adult

Outcome Measures

Primary Outcomes (1)

• Absolute Perihematoma Edema (aPHE) Volume Measured by Computed Tomography (CT) Scan After Intracerebral Hemorrhage (ICH)

  Following the initial diagnostic CT, repeat CT images were obtained between 24-48 h after the diagnostic scan, and on Day 7 and Day 14 to capture the trajectory of PHE increase and plateau after ICH. Only non-contrast study CT scans were obtained on Day 7 and Day 14. The non-contrast scan acquired on each patient at first follow-up (i.e. 24-48 h after the diagnostic scan) served as the baseline for our analysis. All CT scans were uploaded through a secure server, and edema and hematoma volumes were measured in a semi-automated manner by one Central Reader.

  On Day 14 following ICH

Secondary Outcomes (1)

• Plasma BAF312 Concentrations

  Days 1, 8, and 14

Study Arms (2)

BAF312

EXPERIMENTAL

Days 1 - 7, IV up titration; days 8 - 14, 10 mg (5 x 2 mg tablets) taken daily orally

Drug: BAF312 solution; Drug: BAF312 tablet

Placebo

PLACEBO COMPARATOR

Days 1 - 7, IV up titration; days 8 - 14, 10 mg (5 x 2 mg tablets) taken daily orally - matching placebo

Drug: Matching Placebo for BAF312 solution; Drug: Matching Placebo for BAF312 tablet

Interventions

BAF312 solution DRUG

Solution for intravenous (IV) infusion - 4.5mg/4.5mL

Also known as: Siponimod

BAF312

Matching Placebo for BAF312 solution DRUG

Solution for intravenous (IV) infusion - 0mg/4.5mL matching placebo

Placebo

BAF312 tablet DRUG

2 mg film-coated tablet

Also known as: Siponimod

BAF312

Matching Placebo for BAF312 tablet DRUG

0 mg film-coated tablet matching placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients aged 18 to 85 years (inclusive).
• Written informed consent obtained before any study assessment is performed. If the patient is not able to give the informed consent personally, consent by a relative or legal representative is acceptable.
• Spontaneous, supratentorial intracerebral hemorrhage in cerebral cortex or deep brain structures (putamen, thalamus, caudate, and associated deep white matter tracts) with a volume ≥ 10 mL but ≤ 60 mL (calculated by the ABC/2 method, after Kothari et al 1996) determined by routine clinical MRI or CT.
• Patients with the onset of ICH witnessed and/or last seen healthy no longer than 24 hrs previously.
• Patients with Glasgow Coma Scale (GCS) best motor score no less than 5 (brings hands above clavicle on stimulus to head or neck).

You may not qualify if:

• Use of other investigational drugs within 5 half-lives of enrollment, or until the expected pharmacodynamic effect has returned to baseline (for biologics), whichever is longer.
• History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes (e.g., fingolimod).
• Current use of concomitant medications with potent CYP2C9/3A4 inhibitory or induction potential.
• Infratentorial (midbrain, pons, medulla, or cerebellum) ICH.
• Candidates for surgical hematoma evacuation or other urgent surgical intervention (i.e., surgical relief of increased intracranial pressure) on initial presentation. If during the treatment period surgical hematoma evacuation or surgical intervention to lower intracranial pressure becomes indicated, the investigational treatment should be stopped.
• Patients with intraventricular hemorrhage (IVH) having a Graeb score of \>3 on initial presentation. Patients must not have blood in the 4th ventricle and may only have blood in the 3rd ventricle in the absence of ventricular expansion. Trace or mild hemorrhage in either or both lateral ventricles is permitted. Patients with hydrocephalus determined radiologically on initial presentation are excluded regardless of Graeb score.
• Secondary ICH due to:
• aneurysm
• brain tumor
• arteriovenous malformation
• thrombocytopenia, defined as platelet count of \<150,000/µl
• known history of coagulopathy
• acute sepsis
• traumatic brain injury (TBI)
• disseminated intravascular coagulation (DIC)

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (11)

Novartis Investigative Site

Palo Alto, California, 94304, United States

Location

Novartis Investigative Site

New Haven, Connecticut, 06520, United States

Location

Novartis Investigative Site

Atlanta, Georgia, 30303, United States

Location

Novartis Investigative Site

Baltimore, Maryland, 21201, United States

Location

Novartis Investigative Site

Detroit, Michigan, 48202, United States

Location

Novartis Investigative Site

Cincinnati, Ohio, 45219, United States

Location

Novartis Investigative Site

Portland, Oregon, 97239, United States

Location

Novartis Investigative Site

Philadelphia, Pennsylvania, 19104-4283, United States

Location

Novartis Investigative Site

Houston, Texas, 77024, United States

Location

Novartis Investigative Site

Houston, Texas, 77030-3900, United States

Location

Novartis Investigative Site

Charlottesville, Virginia, 22908, United States

Location

Related Links

• A Plain Language Trial Summary is available on novctrd.com

MeSH Terms

Conditions

Hemorrhagic Stroke; Cerebral Hemorrhage; Stroke

Interventions

siponimod

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Intracranial Hemorrhages; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

+ 1 862 778 8300

Study Officials

• Kevin N. Sheth, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a randomized, patient- and investigator-blinded, placebo-controlled, parallel group study of BAF312 on top of standard-of-care for ICH, consisting of 3 epochs: Screening/Baseline, Treatment (Day 1-14), and Follow-Up (to Day 90)

Study Record Dates

• First Submitted: November 8, 2017
• First Posted: November 9, 2017
• Study Start: December 24, 2017
• Primary Completion: May 13, 2020
• Study Completion: May 13, 2020
• Last Updated: August 12, 2022
• Results First Posted: June 7, 2021

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will share

Locations

US (11)