Evaluation of the Efficacy and Safety of Clazosentan in Reversing Cerebral Vasospasm in Adult Subjects With Aneurysmal Subarachnoid Hemorrhage

NCT02560532 | Completed Phase 2

• 2 other identifiers: AC-054-2032015-002721-18
• Study Type: interventional
• Target: 25
• Locations: 3 countries
• Sites: 11

Brief Summary

The purpose of this study is to evaluate the safety and potential therapeutic benefit of use of clazosentan in reversing cerebral vasospasm (a narrowing of blood vessels in the brain due to the presence of blood in the space around the brain) in patients who have suffered a condition known as aneurysmal subarachnoid hemorrhage caused by bleeding onto the surface of the brain from a ruptured brain aneurysm

Conditions

Aneurysmal Subarachnoid Hemorrhage

Keywords

aneurysmal subarachnoid hemorrhage; cerebral vasospasm; clazosentan

Outcome Measures

Primary Outcomes (1)

• Successful reversal of global cerebral vasospasm 3 hours post-study drug initiation

  Successful reversal is defined as an improvement in at least one level of severity on the "global vasospasm assessment" (i.e., from severe to moderate, mild, or none, or from moderate to mild or none), evaluated on Digital subtraction angiogram (DSA)

  3 hours post-study drug initiation

Secondary Outcomes (3)

• Successful reversal of global cerebral vasospasm 24 hours post-study drug initiation

  24 hours post-study drug initiation

• Maximum change from baseline in angiographic cerebral circulation time (CCT)

  At baseline, 3 hours and 24 hours post-study drug initiation

• Number of subjects with adverse events

  Up to 30 days after study drug discontinuation

Study Arms (1)

Clazosentan

EXPERIMENTAL

Diluted solution administered as a continuous intravenous infusion at a rate of 15 mg/h for up to a cumulative maximum of 10 days

Drug: Clazosentan

Interventions

Clazosentan DRUG

Concentrated solution for intravenous injection

Also known as: ACT-108475

Clazosentan

Eligibility Criteria

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

You may qualify if:

• Signed informed consent from the subject or proxy/legal representative
• Aneurysmal subarachnoid hemorrhage (aSAH)confirmed by digital subtraction angiogram (DSA) or computed tomography angiogram (CTA), successfully secured by surgical clipping or endovascular coiling within 72 hours of rupture
• World Federation of Neurological Surgeons (WFNS) grade 1-4 at admission, and which must not increase to grade 5 at the time of enrollment
• Moderate or severe global cerebral vasospasm at the time of enrollment, documented by digital subtraction angiography (DSA) performed not earlier than 48 hours post aneurysm-securing procedure
• Women of childbearing potential must have a negative serum pregnancy test at screening and must use a reliable method of contraception from hospital discharge up to 30 days after discontinuation of study drug infusion, and fertile males must use a condom as a contraceptive method during this same period

You may not qualify if:

• SAH due to causes other than a saccular aneurysm
• Any moderate or severe cerebral vasospasm on angiography prior to the aneurysm-securing procedure
• Presence of a new or worsened cerebral infarct or evidence of significant bleeding post aneurysm-securing procedure, or re-bleeding, on a CT scan performed within 24 hours prior to enrollment
• Total bilirubin \> 2 times the upper limit of normal, and / or a known diagnosis or clinical suspicion of liver cirrhosis or moderate to severe hepatic impairment
• Any severe or unstable concomitant condition or disease (e.g., cancer, hematological, or coronary disease) or chronic condition (e.g., drug abuse, severe alcoholism), which, in the opinion of the investigator, would interfere with the assessment of the safety or effect of the study treatment

Sponsors & Collaborators

• Idorsia Pharmaceuticals Ltd.: lead

Study Sites (11)

Site 2002

Helsinki, 00260, Finland

Location

Site 1002

Bron, 69677, France

Location

Site 1006

Clermont-Ferrand, 63003, France

Location

Site 1004

Marseille, 13385, France

Location

Site 1005

Montpellier, 34295, France

Location

Site 1001

Paris, 75013, France

Location

Site 3005

Aarau, 5001, Switzerland

Location

Site 3001

Basel, 4031, Switzerland

Location

Site 3003

Bern, 3010, Switzerland

Location

Site 3004

Geneva, 1211, Switzerland

Location

Site 3002

Zurich, 8091, Switzerland

Location

MeSH Terms

Conditions

Subarachnoid Hemorrhage; Vasospasm, Intracranial

Interventions

clazosentan

Condition Hierarchy (Ancestors)

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

Study Officials

• Angelina Marr, BSc. Pharm

  Actelion

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2015
• First Posted: September 25, 2015
• Study Start: March 1, 2016
• Primary Completion: May 2, 2017
• Study Completion: May 2, 2017
• Last Updated: July 10, 2018

Record last verified: 2018-07

Locations

FR (5); CH (5); FI (1)