Clinical trial NCT02687191: Safety and Tolerability of PF-05230907 in Intracerebral Hemorrhage
Official title: A PHASE 1B MULTICENTER, OPEN-LABEL STUDY TO EVALUATE THE SAFETY AND TOLERABILITY AND DETERMINE THE MAXIMUM TOLERATED DOSE OF PF-05230907 IN SUBJECTS WITH INTRACEREBRAL HEMORRHAGE (ICH)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Intracerebral Hemorrhage
Keywords: safety, maximum tolerated dose, modified continual reassessment method, intracerebral, hemorrhage, hematoma
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2016-02-22
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study employs a modified continual reassessment method (mCRM) design to estimate the maximum tolerated dose (MTD) of PF-05230907, defined as a target toxicity rate of 15% based on treatment emergent thromboembolic and/or ischemic events (TIEs). The mCRM design utilizes Bayesian methodology to continuously learn the dose-toxicity relationship, which is characterized by a parametric model.

Subjects with a diagnosis of ICH (determined by computed tomography) will be enrolled in cohorts of 3. The total length of time planned for study participation is approximately 3 months; 6.0 hours for screening, a single dose administration with a 4-day minimum hospital confinement period and follow-up visits through Day 91.

Severity of adverse events (AEs) and serious adverse events (SAEs) will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. All subjects who receive PF-05230907 are evaluable for TIEs. The determination of MTD using mCRM modeling will be based on TIEs which occur through 7 days post-dose (Day 8).


Eligibility criteria: Inclusion Criteria:

* ICH as documented by CT scan within 6.0 hours of symptom onset
* Baseline ICH volume \> 5mL and \< 60 mL

Exclusion Criteria:

* Deep coma (Glasgow Coma Scale \< 6)
* Modified Rankin Score \> 3 prior to ICH onset
* Known history of schemic, vaso-occlusive or thrombotic events within 6 months prior to screening
* Known prothrombotic disorders
* Known secondary ICH related to aneurysm, arteriovenous malformation, subarachnoid hemorrhage, trauma, or other causes. CT angiography, MR, or other diagnostic studies obtained as part of the standard of care may be used to assess eligibility.
* Known use of oral anticoagulant(s)
* Known use of low-molecular weight heparin or heparin

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Thromboembolic and/or Ischemic Events (TIEs)
timeFrame: Day 1 through day of discharge (Day 8)
measure: Number of Participants With Treatment-Emergent Serious Adverse Events (SAEs)
timeFrame: Day 1 through follow-up visit (Day 43)
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs)
timeFrame: Day 1 through day of discharge (Day 8)
measure: Number of Participants With Treatment-Emergent Laboratory Abnormalities
timeFrame: Day 1 through Day 8 (or discharge) for D-dimer laboratory test and urinalysis; Day 1 through Day 4 for all other laboratory tests
measure: Number of Participants With Changes From Baseline in Physical Examination
timeFrame: Baseline (pre-dose), Day 2, Day 3, Day 4, Day 8/discharge
measure: Change From Baseline for Body Temperature
timeFrame: Baseline (pre-dose), Day 1 (5 and 45 minutes [min] post-dose), Day 2, Day 3, Day 4, Day 8/discharge
measure: Change From Baseline for Supine Respiratory Rate
timeFrame: Baseline (pre-dose), Day 1 (5 and 45 minutes [min] post-dose), Day 2, Day 3, Day 4, Day 8/discharge
measure: Change From Baseline for Supine Systolic and Diastolic Blood Pressure
timeFrame: Baseline (pre-dose), Day 1 (5 and 45 minutes [min] post-dose), Day 2, Day 3, Day 4, Day 8/discharge
measure: Change From Baseline for Supine Pulse Rate
timeFrame: Baseline (pre-dose), Day 1 (5 and 45 minutes [min] post-dose), Day 2, Day 3, Day 4, Day 8/discharge
measure: Number of Participants With Electrocardiogram (ECG) Qualitative Results
timeFrame: Baseline (pre-dose), Day 2, Day 4, Day 8/discharge
Secondary outcomes:
measure: Maximum Changes From Baseline for Activated Partial Thromboplastin Time (aPTT)
timeFrame: Baseline (pre-dose), Day 2
measure: Maximum Changes From Baseline for Prothrombin Fragment 1+2 (PF1+2)
timeFrame: Baseline (pre-dose), Day 2
measure: Number of Participants With Anti-Drug Antibody (ADA) Production
timeFrame: Day 1 up to follow-up visit (Day 43 and/or Day 91)
measure: Number of Participants With Neutralizing Antibody (NAb) Production
timeFrame: Day 1 up to follow-up visit (Day 43 and/or Day 91)
measure: Number of Participants With Depletion of Coagulation Factor X
timeFrame: Baseline (pre-dose), Day 43, Day 91
Other outcomes:
measure: Change From Baseline in Intracerebral Hemorrhage (ICH) Volume at 24 Hours
timeFrame: Baseline (pre-dose), 24 hours
measure: PF-05230907 Concentration in Plasma
timeFrame: Day 1 pre-dose, 5 and 45 minutes post-dose
measure: Number of Participants With Anti-Chinese Hamster Ovary (CHO) Protein Antibody Production
timeFrame: Day 1, Day 43
measure: Number of Participants With Anti-Paired Basic Amino Acid Cleaving Enzyme (PACE) Furin Antibody Production
timeFrame: Day 1, Day 43
measure: Neurological Function as Assessed by the National Institute of Health Stroke Scale (NIHSS)
timeFrame: Screening, Day 1, Day 2, Day 4, Day 43, and Day 91
measure: Health Resource Utilization Surrogate Measures - Maximum Duration
timeFrame: Day 1 up to Day 91
Locations:
city: Saint Louis
country: United States
facility: Barnes Jewish Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University,
state: Missouri
city: Columbus
country: United States
facility: James Cancer Hospital and Solove Research Institute
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Columbus
country: United States
facility: Martha Morehouse Medical Plaza
state: Ohio
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Montreal
country: Canada
facility: Montreal Neurological Institute and Hospital
state: Quebec
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
state: Barcelona
city: Santiago de Compostela
country: Spain
facility: Hospital Clínico Universitario de Santiago de Compostela, Area Neurovascular-Neurologia
state: LA Coruna
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron, Unidad de Ictus
city: Girona
country: Spain
facility: Hospital Universitari Dr. Josep Trueta IDIBGI, Department Neurology
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: London
country: United Kingdom
facility: University College Hospital
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Silva Blas Y, Diringer MN, Lo B, Masjuan J, Perez de la Ossa N, Cardinal M, Yong F, Zhu T, Li G, Arkin S. Phase 1b Study to Evaluate Safety, Tolerability, and Maximum Tolerated Dose of PF-05230907 for Intracerebral Hemorrhage. Stroke. 2021 Jan;52(1):294-298. doi: 10.1161/STROKEAHA.120.029789. Epub 2020 Dec 4.