Hemorrhagic StrokePhase 2NCT03338998
Efficacy, Safety and Tolerability of BAF312 Compared to Placebo in Patients With Intracerebral Hemorrhage (ICH).
A Phase 2 study testing BAF312 solution and BAF312 tablet in people with Hemorrhagic Stroke and Intracerebral Hemorrhage (ICH), run by Novartis Pharmaceuticals at 11 sites in United States.
Trial 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) Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Hemorrhagic Stroke, Intracerebral Hemorrhage (ICH)
- What is being tested?
- BAF312 solution and BAF312 tablet
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 11 sitesUnited States
- Study dates
- 24 Dec 2017to 13 May 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
- 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.
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- 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.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
Novartis Investigative Site
Atlanta, Georgia, 30303
Novartis Investigative Site
Baltimore, Maryland, 21201
Novartis Investigative Site
Charlottesville, Virginia, 22908
Novartis Investigative Site
Cincinnati, Ohio, 45219
Novartis Investigative Site
Detroit, Michigan, 48202
Novartis Investigative Site
Houston, Texas, 77024
Novartis Investigative Site
Houston, Texas, 77030-3900
Novartis Investigative Site
New Haven, Connecticut, 06520
Novartis Investigative Site
Palo Alto, California, 94304
Novartis Investigative Site
Philadelphia, Pennsylvania, 19104-4283
Novartis Investigative Site
Portland, Oregon, 97239
About this study
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)
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)
Read the detailed description
This was the first trial of BAF312 in ICH patients to evaluate if BAF312 had the potential to limit brain inflammation after ICH, and thereby improve neurological outcome for stroke patients when administered in addition to standard of care.
ICH patients meeting study criteria were randomized at 1:1 ratio into either active or placebo group. Patients received an intravenous infusion (i.v.) treatment within 24 hours of an ICH event and were up titrated for 7 days. Following the i.v. treatment, participants received 10 mg BAF312 or placebo in tablet form (taken daily orally) for an additional 7 days. Participants were followed for an additional 76 days after treatment for neurological and safety conditions during three clinic visits.
Recruitment for the trial was put on hold due to the COVID-19 pandemic. Thirty-two patients had been enrolled in the trial and completed the protocol as planned. After seven months of the trial being on hold, an Interim analysis was conducted and reviewed by the Data Monitoring Committee. Novartis terminated the trial due to lack of potential efficacy.
- Conditions
- Hemorrhagic Stroke, Intracerebral Hemorrhage (ICH)
- Being tested
- BAF312 solution, Matching Placebo for BAF312 solution, BAF312 tablet, Matching Placebo for BAF312 tablet
- Keywords
- stroke, intracerebral hemorrhage, ICH, BAF312, siponimod, sphingosine-1-phosphate receptor, adult
- Medical subject headings
- Hemorrhagic Stroke, Cerebral Hemorrhage, Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BAF312 solutionDrug
Also called Siponimod
Solution for intravenous (IV) infusion - 4.5mg/4.5mL
Matching Placebo for BAF312 solutionDrug
Solution for intravenous (IV) infusion - 0mg/4.5mL matching placebo
BAF312 tabletDrug
Also called Siponimod
2 mg film-coated tablet
Matching Placebo for BAF312 tabletDrug
0 mg film-coated tablet matching placebo
| Study group | Role | What they receive |
|---|---|---|
| BAF312 | Experimental | Days 1 - 7, IV up titration; days 8 - 14, 10 mg (5 x 2 mg tablets) taken daily orally Receives: 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 Receives: Drug: Matching Placebo for BAF312 solution; Drug: Matching Placebo for BAF312 tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: On Day 14 following ICH
Secondary outcomes (1)
Plasma BAF312 Concentrations
Blood samples will be collected to assess plasma concentrations.
Measured: Days 1, 8, and 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2017
- Study start24 Dec 2017
- Primary completion13 May 2020
- Study completion13 May 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hemorrhagic StrokeStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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 blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Kevin N. Sheth, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03338998
- Sponsor's protocol ID
- CBAF312X2207
- Status last verified
- Aug 2022
- First submitted
- 8 Nov 2017
- Last updated
- 12 Aug 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT03338998
- Acronym / sponsor ID
- CBAF312X2207
- Conditions
- Hemorrhagic Stroke, Intracerebral Hemorrhage (ICH)
- Keywords
- stroke, intracerebral hemorrhage, ICH, BAF312, siponimod, sphingosine-1-phosphate receptor, adult
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 24 Dec 2017 (actual)
- Primary completion
- 13 May 2020 (actual)
- Study completion
- 13 May 2020 (actual)
- First posted
- 9 Nov 2017 (actual)
- Results
- Posted 7 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
Detailed description
This was the first trial of BAF312 in ICH patients to evaluate if BAF312 had the potential to limit brain inflammation after ICH, and thereby improve neurological outcome for stroke patients when administered in addition to standard of care.
ICH patients meeting study criteria were randomized at 1:1 ratio into either active or placebo group. Patients received an intravenous infusion (i.v.) treatment within 24 hours of an ICH event and were up titrated for 7 days. Following the i.v. treatment, participants received 10 mg BAF312 or placebo in tablet form (taken daily orally) for an additional 7 days. Participants were followed for an additional 76 days after treatment for neurological and safety conditions during three clinic visits.
Recruitment for the trial was put on hold due to the COVID-19 pandemic. Thirty-two patients had been enrolled in the trial and completed the protocol as planned. After seven months of the trial being on hold, an Interim analysis was conducted and reviewed by the Data Monitoring Committee. Novartis terminated the trial due to lack of potential efficacy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- 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)
| Arm | Type | Receives |
|---|---|---|
| BAF312 | Experimental | Drug: BAF312 solution, Drug: BAF312 tabletDays 1 - 7, IV up titration; days 8 - 14, 10 mg (5 x 2 mg tablets) taken daily orally |
| Placebo | Placebo comparator | Drug: Matching Placebo for BAF312 solution, Drug: Matching Placebo for BAF312 tabletDays 1 - 7, IV up titration; days 8 - 14, 10 mg (5 x 2 mg tablets) taken daily orally - matching placebo |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (32 listed)
- 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.
- Infratentorial (midbrain, pons, medulla, or cerebellum) ICH.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BAF312 solutionAlso: SiponimodSolution for intravenous (IV) infusion - 4.5mg/4.5mL | Drug | BAF312 |
| Matching Placebo for BAF312 solutionSolution for intravenous (IV) infusion - 0mg/4.5mL matching placebo | Drug | Placebo |
| BAF312 tabletAlso: Siponimod2 mg film-coated tablet | Drug | BAF312 |
| Matching Placebo for BAF312 tablet0 mg film-coated tablet matching placebo | Drug | Placebo |
Primary outcome
Absolute Perihematoma Edema (aPHE) Volume Measured by Computed Tomography (CT) Scan After Intracerebral Hemorrhage (ICH)
Time frame: On Day 14 following 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.
1 secondary outcome
Plasma BAF312 Concentrations
Time frame: Days 1, 8, and 14
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- A Plain Language Trial Summary is available on novctrd.comLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kevin N. Sheth, MD principal investigator
Yale University
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BAF312 solution and BAF312 tablet in people with Hemorrhagic Stroke and Intracerebral Hemorrhage (ICH), run by Novartis Pharmaceuticals at 11 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Absolute Perihematoma Edema (aPHE) Volume Measured by Computed Tomography (CT) Scan After Intracerebral Hemorrhage (ICH) (time frame: On Day 14 following ICH). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2022.