Clinical Trial: A Phase 1 Study of ProMetic Plasminogen (Human) Intravenous in Adults and Children With Plasminogen Deficiency

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase 1, Dose Escalation, and Pharmacokinetic Study of ProMetic Plasminogen Administered as Intravenous Infusion in Adults and Children With Hypoplasminogenemia

Brief Summary: ProMetic is intiitating a first-in-man study entitled "A Phase 1, Dose Escalation, and Pharmacokinetic Study of ProMetic Plasminogen Administered as Intravenous Infusion in Adults and Children with Hypoplasminogenemia". The general objectives of this clinical study, (Protocol #2002C005G), are to determine the optimal dose and interval required to support the planned Phase 2/3 study and to investigate initial safety and tolerability.

Detailed Summary:

The Phase 1 study will be a single center study, the subjects will be from across country. It is an open-label, single-arm, dose-escalation study in patients with hypoplasminogenemia aged 12 years and older.

Three dose cohorts are planned to achieve a target sample size of 12 evaluable subjects. This will ensure a minimum of 4 evaluable subjects in each cohort. Due to the challenges of patient availability and burden of cross country travel, each cohort will enroll no more than 6 subjects. Any subject may participate in multiple cohorts, as judged appropriate by the investigator.

In each cohort, each subject must be diagnosed with hypoplasminogenimia and have a plasminogen activity level of ≤ 40% before they will be administered a single dose of Plasminogen (Human), the investigational medicinal product. Plasminogen will be administered as an intravenous (IV) infusion at the following doses:

  • Cohort 1: 2 mg/kg
  • Cohort 2: 6 mg/kg
  • Cohort 3*: 12 mg/kg * Optional. If optimal dosing information is demonstrated in either Cohort 1 or 2, Cohort 3 will not be pursued.

At each dose level, Plasma plasminogen activity and antigen levels will be measured to develop a pharmacokinetic profile. Blood samples will be drawn at the following time points: baseline immediately before dosing; at the end of infusion; and at 1, 6, 24, 48, 72, 96, 120, 168, and 216 hours after the end of infusion. Visits 1-4 and 11 must be conducted at the clinical site. A subject may conduct Visits 5-10 at the clinical site or have the study procedures performed by a Home Health Nurses Group (HHNG) nurse through home visits, if continued visits to the st
Sponsor: ProMetic BioTherapeutics, Inc

Current Primary Outcome: Pharmacokinetic (PK) profile of lyophilized plasminogen (PLG). Area under the concentration time curve (both AUC0-t and AUC0-inf), maximum plasma concentration (Cmax), volume of distribution (Vd), clearance (Cl), and mean residence time (MRT). [ Time Frame: 8 months ]

The following PK parameters will be calculated from PLG activity and antigen levels using the non-compartmental PK analysis method: Area under the concentration time curve (both AUC0-t and AUC0-inf), maximum plasma concentration (Cmax), volume of distribution (Vd), clearance (Cl), and mean residence time (MRT). Pharmacokinetic (PK) profile of lyophilized plasminogen (PLG) at 3 dose levels (the third dose is optional) in subjects with hypoplasminogenemia to determine the desirable dose and dosing interval to be studied in a Phase 2/3 study.


Original Primary Outcome: Same as current

Current Secondary Outcome: To evaluate the safety and tolerability of PLG in subjects with hypoplasminogenemia, as measured by Rate, severity, and relatedness of any adverse events. [ Time Frame: 8 months ]

Rate, severity, and relatedness of any adverse events. Changes from baseline observed or reported in medical history, vital signs, physical exam, clinical laboratory tests. Assessment of development of antibodies against plasminogen.


Original Secondary Outcome: Same as current

Information By: ProMetic BioTherapeutics, Inc

Dates:
Date Received: December 4, 2014
Date Started: December 2014
Date Completion:
Last Updated: February 11, 2016
Last Verified: December 2015