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

This study is not yet open for participant recruitment.
Verified November 2017 by Novartis ( Novartis Pharmaceuticals )
Sponsor:
ClinicalTrials.gov Identifier:
NCT03338998
First Posted: November 9, 2017
Last Update Posted: November 9, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
  Purpose

This is a randomized, placebo-controlled, subject- and investigator-blinded trial of BAF312 in intracerebral hemorrhage (ICH) patients to study efficacy, safety, and tolerability. BAF312 is a drug that could potentially limit brain inflammation after ICH, and thereby improve neurological outcome for hemorrhagic stroke patients.

In this study, ICH patients meeting study criteria will be randomized at 1:1 ratio into either active or placebo group. The first i.v. treatment must starts within 24 hours of ICH event. Participating patients will also be followed up for additional 76 days after treatment on neurological and safety conditions in 3 clinic visits.

BAF312 treatment includes the following identified risks: transient effects on heart rate and rhythm (bradyarrhythmia and 2nd degree AV block) at treatment initiation that are completely avoided by initial up-titration; liver enzyme elevation; lymphopenia due to lymphocyte redistribution (expected effect of BAF312); macular edema; and varicella zoster (VZV) infection.


Condition Intervention Phase
Hemorrhagic Stroke Intracerebral Hemorrhage (ICH) Drug: BAF312 Drug: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
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)
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description:
Subject- and investigator-blinded
Primary Purpose: Treatment
Official Title: A Phase II, Patient and Investigator-blinded, Randomized, Placebo-controlled Study to Evaluate Efficacy, Safety and Tolerability of BAF312 in Patients With Stroke Due to Intracerebral Hemorrhage (ICH)

Resource links provided by NLM:


Further study details as provided by Novartis ( Novartis Pharmaceuticals ):

Primary Outcome Measures:
  • modified Rankin Scale (mRS) score [ Time Frame: Day 90 ]
    The mRS consists of 6 grades of disability, higher scores indicating more severe disability (0 = asymptomatic, 6 = dead). A patient with a favorable outcome is defined as a patient with a mRS score of 0, 1 or 2.


Secondary Outcome Measures:
  • Plasma BAF312 concentrations [ Time Frame: Days 1, 8, and 14 ]
    Blood samples will be collected to assess plasma concentrations.


Estimated Enrollment: 100
Anticipated Study Start Date: December 14, 2017
Estimated Study Completion Date: March 9, 2020
Estimated Primary Completion Date: March 9, 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BAF312
Days 1 - 7, IV uptitration; days 8 - 14, final daily dose administered orally"
Drug: BAF312
Supplied as an i.v. solution for days 1 through 7 and as a tablet for days 8 through 14
Placebo Comparator: Placebo
Days 1 through 7: i.v. matching placebo Days 8 through 14: p.o. matching placebo QD
Drug: Placebo
Supplied as an i.v. solution for days 1 through 7 and as tablets for days 8 through 14

Detailed Description:

This is the first trial of BAF312 in ICH patients to study efficacy, safety, and tolerability, compared to placebo. BAF312 is a drug that could potentially limit brain inflammation after ICH, and thereby improve neurological outcome for stroke patients.

In this study, ICH patients meeting study criteria will be randomized at 1:1 ratio into either active or placebo group. The first i.v. treatment must starts within 24 hours of ICH event. Participating patients will also be followed up for additional 76 days after treatment on neurological and safety conditions in 3 clinic visits.

BAF312 treatment includes the following identified risks: transient effects on heart rate and rhythm (bradyarrhythmia and 2nd degree AV block) at treatment initiation that are completely avoided by initial up-titration; liver enzyme elevation; lymphopenia due to lymphocyte redistribution (expected effect of BAF312); macular edema; and varicella zoster (VZV) infection.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

ICH patients eligible for inclusion in this study must fulfill all of the following criteria:

  1. Male or female patients aged 18 to 80 years (inclusive).
  2. 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.
  3. Spontaneous, supratentorial intracerebral hemorrhage in deep brain structures (putamen, thalamus, caudate, and associated deep white matter tracts) with a volume ≥ 10 mL but ≤ 30 mL (calculated by the ABC/2 method, after Kothari et al 1996) determined by routine clinical MRI or CT.
  4. Patients with the onset of ICH witnessed and/or last seen healthy no longer than 24 hrs previously.
  5. Patients with Glasgow Coma Scale (GCS) best motor score no less than 6.

Exclusion Criteria:

ICH patients fulfilling any of the following criteria are not eligible for inclusion in this study:

  1. 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.
  2. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes (e.g., fingolimod).
  3. Current use of concomitant medications with potent CYP2C9/3A4 inhibitory or induction potential.
  4. Necessity for mechanical ventilation at screening.
  5. Infratentorial (midbrain, pons, medulla, or cerebellum) or superficial cortical (lobar) ICH.
  6. 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.
  7. Patients with intraventricular hematoma extension, with or without hydrocephalus, on initial presentation.
  8. 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)
  9. Prior disability due to other disease compromising mRS evaluation, thereby interfering with the primary outcome, operationally defined as an estimated mRS score (by history) of ≥ 3 before ICH.
  10. Preexisting unstable epilepsy.
  11. Patients with active systemic bacterial, viral or fungal infections.
  12. Concomitant drug-related exclusion criteria:

    • Intravenous immunoglobulin, immunosuppressive and/or chemotherapeutic medications.
    • Moderate immunosuppressives (e.g. azathioprine, methotrexate) and/or fingolimod within 2 months prior to randomization.
    • Stronger immunosuppressives (e.g. cyclophosphamide, immunosuppressive mAb) within (minimally) 6 months prior to randomization, or longer with long-lasting immunosuppressive medications as determined by the investigator.
  13. Cardiovascular exclusion criteria:

    • Cardiac conduction or rhythm disorders including sinus arrest or sino-atrial block, heart rate <50 bpm, sick-sinus syndrome, Mobitz Type II second degree AV block or higher grade AV block, or preexisting atrial fibrillation (either by history or observed at screening).
    • PR interval >220 msec. Long QT syndrome or QTcF prolongation >450 msec in males or >470 msec in females on screening electrocardiogram (ECG).
    • Patients receiving treatment with QT-prolonging drugs having a long half-life (e.g., amiodarone).
  14. Any of the following abnormal laboratory values prior to randomization:

    • White blood cell (WBC) count < 2,000/μl (< 2.0 x 109/L)
    • Lymphocyte count < 800/μl (< 0.8 x 109/L)
  15. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
  16. Patients with any other medically unstable condition or serious laboratory abnormality as determined by the investigator.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03338998


Contacts
Contact: Novartis Pharmaceuticals +41613241111 novartis.email@novrtis.com
Contact: Novartis Pharmaceuticals

Sponsors and Collaborators
Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03338998     History of Changes
Other Study ID Numbers: CBAF312X2207
First Submitted: November 8, 2017
First Posted: November 9, 2017
Last Update Posted: November 9, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
stroke
intracerebral hemorrhage
ICH
BAF312
siponimod
sphingosine-1-phosphate receptor

Additional relevant MeSH terms:
Stroke
Hemorrhage
Cerebral Hemorrhage
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Intracranial Hemorrhages