Safety/Pharmacokinetic Study Comparing Intracisternal EG-1962 to Standard of Care Enteral Nimodipine in Adults With aSAH

NCT02893826 | Terminated Phase 1

• 1 other identifier: EG-01-1962-04
• Study Type: interventional
• Target: 6
• Locations: 2 countries
• Sites: 4

Brief Summary

Safety and Pharmacokinetic study comparing intracisternal EG-1962 to enternal nimopidine in the treatment of aneurysmal subarachnoid hemorrhage.

Conditions

Subarachnoid Hemorrhage, Aneurysmal

Keywords

Aneurysm; Ruptured; nimodipine; subarachnoid hemorrhage

Outcome Measures

Primary Outcomes (2)

• Incidence and severity of adverse events

  90 Days

• Proportion of subjects with delayed cerebral infarctions present on CT at Day 30

  30 Days

Secondary Outcomes (7)

• Pharmacokinetic (PK) profile of EG-1962 as measured by maximum drug concentration in plasma (Cmax)

  At the time of the first post-operation blood draw and every 6 hours (± 30 minutes) for the first 24 hours and daily thereafter until hospital discharge or Day 21, whichever occurs first and Day 30

• Pharmacokinetic (PK) profile of EG-1962 as measured by time to reach maximum drug concentration in plasma (Tmax)

  At the time of the first post-operation blood draw and every 6 hours (± 30 minutes) for the first 24 hours and daily thereafter until hospital discharge or Day 21, whichever occurs first and Day 30

• Pharmacokinetic (PK) profile of EG-1962 as measured by steady state concentration (Css)

  At the time of the first post-operation blood draw and every 6 hours (± 30 minutes) for the first 24 hours and daily thereafter until hospital discharge or Day 21, whichever occurs first and Day 30

• Pharmacokinetic (PK) profile of EG-1962 as measured by AUC area under the plasma concentration-time curve (AUC) from 0 to 24 hours (AUC024h)

  At the time of the first post-operation blood draw and every 6 hours (± 30 minutes) for the first 24 hours

• Pharmacokinetic (PK) profile of EG-1962 as measured by AUC from 0 to Day 10 (AUC0-10)

  At the time of the first post-operation blood draw and every 6 hours (± 30 minutes) for the first 24 hours and up to Day 10

Other Outcomes (2)

• Extended Glasgow Outcome Scale (GOSE)

  Day 90

• Montreal Cognitive Assessment (MoCA)

  Day 90

Study Arms (2)

EG-1962 Group

EXPERIMENTAL

1 dose of intracisternal EG-1962 (nimodipine microparticles) 600 mg

Drug: EG-1962 (nimodipine microparticles)

Enteral Nimodipine Group

ACTIVE COMPARATOR

Up to a total of 21 days of enteral nimodipine (including nimodipine received prior to randomization)

Drug: Enteral Nimodipine

Interventions

EG-1962 (nimodipine microparticles) DRUG

Also known as: Single intracisternal adminstration

EG-1962 Group

Enteral Nimodipine DRUG

Also known as: Administered for up to 21 days

Enteral Nimodipine Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ruptured saccular aneurysm repaired by neurosurgical clipping
• Subarachnoid hemorrhage on computed tomography (CT) scan of grade 2-4 on the modified Fischer scale
• WFNS grade 1 or 2 assessed during the Pre-randomization Phase. If WFNS grade 2, must not require an EVD prior to aneurysm repair

You may not qualify if:

• Major complication during aneurysm repair such as, but not limited to, massive intraoperative hemorrhage, brain swelling, arterial occlusion or inability to secure the ruptured aneurysm
• Angiographic vasospasm prior to randomization
• Evidence of cerebral infarction with neurological deficit

Sponsors & Collaborators

• Edge Therapeutics Inc: lead

Study Sites (4)

Dignity Health; St. Joseph's Hospital and Medical Center

Phoenix, Arizona, 85013, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

University of Maryland Medical Systems

Baltimore, Maryland, 21201, United States

Location

University of Alberta Hospital/Mackenzie Health Sciences Centre

Edmonton, Alberta, T6G 2B7, Canada

Location

Related Publications (2)

• De BP, Rosenberg JB, Selvan N, Wilson I, Yusufzai N, Greco A, Kaminsky SM, Heier LA, Ricart Arbona RJ, Miranda IC, Monette S, Nair A, Khanna R, Crystal RG, Sondhi D. Assessment of Safety and Biodistribution of AAVrh.10hCLN2 Following Intracisternal Administration in Nonhuman Primates for the Treatment of CLN2 Batten Disease. Hum Gene Ther. 2023 Sep;34(17-18):905-916. doi: 10.1089/hum.2023.067.

  PMID: 37624739 DERIVED

• Macdonald RL, Hanggi D, Ko NU, Darsaut TE, Carlson AP, Wong GK, Etminan N, Mayer SA, Aldrich EF, Diringer MN, Ng D, Strange P, Bleck T, Grubb R, Suarez JI. NEWTON-2 Cisternal (Nimodipine Microparticles to Enhance Recovery While Reducing Toxicity After Subarachnoid Hemorrhage): A Phase 2, Multicenter, Randomized, Open-Label Safety Study of Intracisternal EG-1962 in Aneurysmal Subarachnoid Hemorrhage. Neurosurgery. 2020 Dec 15;88(1):E13-E26. doi: 10.1093/neuros/nyaa430.

  PMID: 32985652 DERIVED

MeSH Terms

Conditions

Subarachnoid Hemorrhage; Aneurysm; Rupture

Interventions

EG-1962

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; Wounds and Injuries

Study Officials

• R. Loch Macdonald, MD, PhD

  Edge Therapeutics Inc

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2016
• First Posted: September 9, 2016
• Study Start: September 1, 2016
• Primary Completion: December 1, 2017
• Study Completion: March 1, 2018
• Last Updated: July 26, 2018

Record last verified: 2018-07

Locations

CA (1); US (3)