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

Brief Title

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

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 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.
    

Study Phase

Phase 1

Study Type

Interventional


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).

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.

Condition

Type I Plasminogen Deficiency

Intervention

Plasminogen (Human) Intravenous

Study Arms / Comparison Groups

 Cohort 1
Description:  low dose group of 2 mg/kg Plasminogen (Human) Intravenous

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

7

Start Date

December 2014

Completion Date

February 2016

Primary Completion Date

December 2015

Eligibility Criteria

        Inclusion Criteria:

          1. Subject has provided informed consent/assent, or the subject's guardian has given
             consent if the subject is under 18 years

          2. Subject is male or female between 12 and 80 years of age, inclusive

          3. Subject has a diagnosis of hypoplasminogenemia evidenced by an abnormal, decreased
             plasminogen activity level, regardless of plasminogen antigen level

          4. Subject has a plasminogen activity level ≤ 40%

          5. Subject has documented immunity to hepatitis A virus (HAV) and hepatitis B virus (HBV)
             or has received the first dose of HAV and HBV vaccine prior to IMP administration and
             is scheduled to receive the second vaccine dose

          6. Subject (male or female of reproductive age) agrees to use contraceptive methods from
             screening through 14 days after administration of IMP unless documented as
             biologically (e.g., post-menopausal, not begun menstruating) or surgically
             (vasectomized) sterile

        Exclusion Criteria:

          1. Subject has a history of severe reactions (e.g., anaphylaxis) to blood or blood
             products that may requiring resuscitation or otherwise prevent study participation in
             the opinion of the investigator

          2. Subject has evidence of uncontrolled hypertension

          3. Subject has clinical or laboratory evidence of an intercurrent infection as evidenced
             by symptoms including fever, tachycardia, or other specific signs and symptoms*

          4. Subject is pregnant and/or lactating

          5. Subject has or has had a malignancy, except for basal and squamous cell skin cancer,
             within 3 years of Baseline

          6. Subject is a previous organ transplant recipient

          7. Subject is receiving exogenous plasminogen (ocular or IV), including laboratory grade
             plasminogen and fresh lyophilized plasma within two weeks of Baseline

          8. Subject has any psychiatric disorder, other mental disorder, or any other medical
             disorder that impairs the subject's ability to give informed consent or to comply with
             the requirements of the study protocol

          9. Subject has experienced a severe adverse event in a prior cohort of this study.

         10. Subject has evidence of renal dysfunction, defined as serum creatinine of > 2 times
             the upper limit of normal

         11. Subject has evidence of hepatic dysfunction, defined as 3 times the upper limit of
             normal in ALT, and/or AST, and/or alkaline phosphatase (ALP)

         12. Subject has participated in another IRB-approved interventional clinical trial of a
             drug, biologic, or device within 30 days of Baseline

         13. Subject has a chronic or acute, clinically significant, inter-current illness (eg,
             cardiac, hepatic, renal, endocrine, neurologic, hematologic, neoplastic,
             immunological, and skeletal) that the investigator determines could interfere with the
             safety or pharmacokinetic assessments for this study

         14. Subject is unable to adhere to the scheduling requirements of the protocol *Note:
             Subjects with an intercurrent infection cannot participate; however, subjects meeting
             this exclusion criterion at the Baseline Visit may return for a repeat Baseline Visit
             once the infection is considered resolved according to the investigator and can be
             included in the cohort that is actively recruiting at that time if all
             inclusion/exclusion criteria are met
      

Gender

All

Ages

12 Years - 80 Years

Accepts Healthy Volunteers

No

Contacts

, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT02312180

Organization ID

2002C005G


Responsible Party

Sponsor

Study Sponsor

Prometic Biotherapeutics, Inc.


Study Sponsor

, , 


Verification Date

August 2017