Efficacy, Safety and Tolerability of BAF312 Compared to Placebo in Patients With Intracerebral Hemorrhage (ICH).
![]() |
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. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT03338998 |
Recruitment Status :
Suspended
(Only recruitment temporarily paused due to Covid-19.)
First Posted : November 9, 2017
Last Update Posted : May 4, 2020
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
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 or disease | Intervention/treatment | Phase |
---|---|---|
Hemorrhagic Stroke Intracerebral Hemorrhage (ICH) | Drug: BAF312 Drug: Placebo | Phase 2 |
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.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 60 participants |
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 (Siponimod) in Patients With Stroke Due to Intracerebral Hemorrhage (ICH) |
Actual Study Start Date : | December 24, 2017 |
Estimated Primary Completion Date : | November 1, 2021 |
Estimated Study Completion Date : | November 1, 2021 |

Arm | Intervention/treatment |
---|---|
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
Other Name: Siponimod |
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 |
- Absolute perihematoma edema (aPHE) [ Time Frame: Day 14 ]aPHE volume measured by CT scans on Day 14 after ICH.
- Plasma BAF312 concentrations [ Time Frame: Days 1, 8, and 14 ]Blood samples will be collected to assess plasma concentrations.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years to 85 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
ICH patients eligible for inclusion in this study must fulfill all of the following criteria:
- 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).
Exclusion Criteria:
ICH patients fulfilling any of the following criteria are not eligible for inclusion in this study:
- 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.
- Intentionally left blank - removed with protocol amendment #2
- 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)
- 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 for patients less than or equal to 80 years of age. For ICH patients 81-85 years of age, estimated mRS by history prior to ICH must be less than or equal to 1 (no significant disability despite symptoms).
- Preexisting unstable epilepsy.
- Patients with active systemic bacterial, viral or fungal infections.
-
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.
-
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).
-
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)
- 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.
- Patients with any other medically unstable condition or serious laboratory abnormality as determined by the investigator.

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
United States, California | |
Novartis Investigative Site | |
Palo Alto, California, United States, 94304 | |
United States, Connecticut | |
Novartis Investigative Site | |
New Haven, Connecticut, United States, 06520 | |
United States, Georgia | |
Novartis Investigative Site | |
Atlanta, Georgia, United States, 30303 | |
United States, Maryland | |
Novartis Investigative Site | |
Baltimore, Maryland, United States, 21201 | |
United States, Michigan | |
Novartis Investigative Site | |
Detroit, Michigan, United States, 48202 | |
United States, New York | |
Novartis Investigative Site | |
New York, New York, United States, 11030 | |
United States, North Carolina | |
Novartis Investigative Site | |
Durham, North Carolina, United States, 27710 | |
United States, Ohio | |
Novartis Investigative Site | |
Cincinnati, Ohio, United States, 45219 | |
United States, Oregon | |
Novartis Investigative Site | |
Portland, Oregon, United States, 97239 | |
United States, Pennsylvania | |
Novartis Investigative Site | |
Philadelphia, Pennsylvania, United States, 19104-4283 | |
United States, Texas | |
Novartis Investigative Site | |
Houston, Texas, United States, 77030-3900 | |
United States, Virginia | |
Novartis Investigative Site | |
Charlottesville, Virginia, United States, 22908 |
Principal Investigator: | Kevin N. Sheth, MD | Yale University |
Responsible Party: | Novartis Pharmaceuticals |
ClinicalTrials.gov Identifier: | NCT03338998 |
Other Study ID Numbers: |
CBAF312X2207 |
First Posted: | November 9, 2017 Key Record Dates |
Last Update Posted: | May 4, 2020 |
Last Verified: | March 2020 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
Plan Description: | Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com |
URL: | https://www.clinicalstudydatarequest.com |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
stroke intracerebral hemorrhage ICH |
BAF312 siponimod sphingosine-1-phosphate receptor |
Stroke Cerebral Hemorrhage Hemorrhage Cerebrovascular Disorders Brain Diseases Central Nervous System Diseases |
Nervous System Diseases Vascular Diseases Cardiovascular Diseases Pathologic Processes Intracranial Hemorrhages |