NCT02687191|TerminatedPhase 1ResultsDMCFDA Drug

Study Stopped

B2341002 was terminated on 26-OCT-2017 for strategic reasons. The decision to terminate the trial was not based on any safety concerns.

Safety and Tolerability of PF-05230907 in Intracerebral Hemorrhage

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)

Pfizer ClinicalTrials.gov

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2 other identifiers

B23410022015-005703-83

Study Type

interventional

Target

Locations

4 countries

Sites

Timeline

RegisteredFeb 2016

StartedNov 2016

CompletionJan 2018

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).

Trial Health

Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at P25-P50 for phase_1

Timeline

Completed

Started Nov 2016

Geographic Reach

4 countries

13 active sites

Status

terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

1.2 years study duration

First Submitted

Initial submission to the registry

February 16, 2016

Completed

6 days until next milestone

First Posted

Study publicly available on registry

February 22, 2016

Completed

8 months until next milestone

Study Start

First participant enrolled

November 1, 2016

Completed

1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2018

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2018

Completed

1.3 years until next milestone

Results Posted

Study results publicly available

April 17, 2019

Completed

Last Updated

April 17, 2019

Status Verified

April 1, 2019

Enrollment Period

1.2 years

First QC Date

February 16, 2016

Results QC Date

October 25, 2018

Last Update Submit

April 15, 2019

Conditions

Intracerebral Hemorrhage

Keywords

safety, maximum tolerated dose, modified continual reassessment method, intracerebral, hemorrhage, hematoma

Outcome Measures

Primary Outcomes (10)

Number of Participants With Treatment-Emergent Thromboembolic and/or Ischemic Events (TIEs)
Thromboembolic and/or ischemic events (TIEs) were defined as any of the following events: disseminated intravascular coagulation (Grade \[Gr\]\>=3); acute coronary syndrome (Gr \>=3); cardiac arrest (Gr \>=4); myocardial infarction (Gr \>=3); Cardiac troponin I increased (Gr 3); ischemia cerebrovascular (Gr \>=1 and associated with lesion\[s\]); portal vein thrombosis (Gr \>=2); ischemic stroke (Gr \>=1 and associated with lesion\[s\]); transient ischemic attacks (Gr 2); purpura (Gr \>=2); superior vena cava syndrome (Gr \>=1); thromboembolic event (Gr \>=2); visceral arterial ischemia (Gr \>=2); peripheral arterial ischemia (Gr \>=3). TIEs were graded based on Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. For the respective event to count as a treatment-emergent TIE, onset or worsening of the event must have occurred following treatment with PF-05230907 and during the interval between Day 1 dosing through Day 8.
Day 1 through day of discharge (Day 8)
Number of Participants With Treatment-Emergent Serious Adverse Events (SAEs)
A serious adverse event (SAE) was any untoward medical occurrence at any dose that: resulted in death; or was life threatening (immediate risk of death); or required inpatient hospitalization or prolongation of existing hospitalization; or resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); or resulted in congenital anomaly/birth defect. Any such events occurring following the start of treatment or increasing in severity were counted as treatment-emergent.
Day 1 through follow-up visit (Day 43)
Number of Participants With Treatment-Emergent Adverse Events (AEs)
An adverse event (AE) was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. For the respective event to count as a treatment-emergent AE, onset or worsening of the event must have occurred following treatment with PF-05230907 and during the interval between Day 1 dosing through Day 8.
Day 1 through day of discharge (Day 8)
Number of Participants With Treatment-Emergent Laboratory Abnormalities
Laboratory safety parameters included hematology, blood chemistry, prothrombin time/international normalized ratio (PT/INR), fibrinogen, antithrombin III (ATIII), Protein S level, Protein C activity, cardiac troponin I, D-dimer, and urinalysis. The number of participants with laboratory test abnormalities meeting specified criteria without regard to baseline abnormality was assessed. Any abnormalities occurring after the administration of treatment and increasing in severity from baseline value were counted as treatment-emergent.
Day 1 through Day 8 (or discharge) for D-dimer laboratory test and urinalysis; Day 1 through Day 4 for all other laboratory tests
Number of Participants With Changes From Baseline in Physical Examination
Comprehensive and targeted physical examinations included general appearance, HEENT (head, eyes, ears, nose and throat), skin, heart (auscultation), lungs (auscultation), abdomen (palpitation and auscultation), and extremities with attention to swelling, general or localized tenderness, entire leg or calf swelling, edema, and collateral superficial veins. The results of the comprehensive and targeted physical examinations were combined to evaluate the changes from baseline through Day 8 (or discharge) for each site parameter according to the categories: positive change (abnormal to normal); no change (normal to normal or abnormal to abnormal); negative change (normal to abnormal). Parameters with at least 1 participant meeting the positive/negative change from baseline criteria are presented here.
Baseline (pre-dose), Day 2, Day 3, Day 4, Day 8/discharge
Change From Baseline for Body Temperature
Body temperature was measured by oral, tympanic, axillary or temporal method.
Baseline (pre-dose), Day 1 (5 and 45 minutes [min] post-dose), Day 2, Day 3, Day 4, Day 8/discharge
Change From Baseline for Supine Respiratory Rate
Respiratory rate was measured after 5 minutes rest in supine position by observing and counting the respirations of the participant for 30 seconds and multiplied by 2. The use of an automated device for measuring respiratory rate was acceptable.
Baseline (pre-dose), Day 1 (5 and 45 minutes [min] post-dose), Day 2, Day 3, Day 4, Day 8/discharge
Change From Baseline for Supine Systolic and Diastolic Blood Pressure
Supine blood pressure (BP, systolic and diastolic) was measured with the participant's arm supported at the level of the heart and recorded to the nearest milliliters of mercury (mmHg) after 5 minutes of rest whenever possible and as permitted by the participant's medical condition.
Baseline (pre-dose), Day 1 (5 and 45 minutes [min] post-dose), Day 2, Day 3, Day 4, Day 8/discharge
Change From Baseline for Supine Pulse Rate
The use of an automated device for measuring pulse rate was acceptable, although, when done manually, pulse rate was measured in the brachial/radial artery for at least 30 seconds.
Baseline (pre-dose), Day 1 (5 and 45 minutes [min] post-dose), Day 2, Day 3, Day 4, Day 8/discharge
Number of Participants With Electrocardiogram (ECG) Qualitative Results
The electrocardiogram (ECG) results over time were compared to baseline and assessed by the investigator as "less abnormal", "no significant change", or "more abnormal".
Baseline (pre-dose), Day 2, Day 4, Day 8/discharge

Secondary Outcomes (5)

Maximum Changes From Baseline for Activated Partial Thromboplastin Time (aPTT)
Baseline (pre-dose), Day 2
Maximum Changes From Baseline for Prothrombin Fragment 1+2 (PF1+2)
Baseline (pre-dose), Day 2
Number of Participants With Anti-Drug Antibody (ADA) Production
Day 1 up to follow-up visit (Day 43 and/or Day 91)
Number of Participants With Neutralizing Antibody (NAb) Production
Day 1 up to follow-up visit (Day 43 and/or Day 91)
Number of Participants With Depletion of Coagulation Factor X
Baseline (pre-dose), Day 43, Day 91

Other Outcomes (6)

Change From Baseline in Intracerebral Hemorrhage (ICH) Volume at 24 Hours
Baseline (pre-dose), 24 hours
PF-05230907 Concentration in Plasma
Day 1 pre-dose, 5 and 45 minutes post-dose
Number of Participants With Anti-Chinese Hamster Ovary (CHO) Protein Antibody Production
Day 1, Day 43
+3 more other outcomes