A Phase 1 Study of ProMetic Plasminogen (Human) Intravenous in Adults and Children With Plasminogen Deficiency
Condition: Type I Plasminogen Deficiency; Hypoplasminogenemia
MeSH terms: Coagulation Protein Disorders
Study type: Interventional
Phase: Phase 1

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 description: 
      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 study site are not possible or practical.

      Subjects will have another visit 14 days after the IV infusion for Visit 10 (Day 15,
      Short-term-Safety Visit). Subjects will return to the clinic 30 days after IV infusion for
      Visit 11 (Day 30, Follow-up-Safety Visit) for the collection of adverse events (AEs),
      immunogenicity testing, routine safety tests and procedures, and final viral safety testing,
      unless the subject is entering into another Cohort.
    

Intervention name(s): Plasminogen (Human) Intravenous
Intervention type(s): Biological
Intervention description(s): Plasma-derived purified plasminogen formulated for intravenous administration
Intervention MeSH terms: Plasminogen
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment