A Study of Prometic Plasminogen IV Infusion in Subjects With Hypoplasminogenemia

Brief Title

A Study of Prometic Plasminogen IV Infusion in Subjects With Hypoplasminogenemia

Official Title

A Phase 2/3, Open-Label, Repeat-Dose Study of the Pharmacokinetics, Efficacy, and Safety of Prometic Plasminogen Intravenous Infusion in Subjects With Hypoplasminogenemia

Brief Summary

      This is a Phase 2/3 pivotal study to evaluate pharmacokinetics (PK), efficacy, and safety of
      Prometic Plasminogen (Human) Intravenous Lyophilized Solution, the investigational medicinal
      product (IMP), in pediatric and adult subjects with hypoplasminogenemia.
    

Detailed Description

      This is a Phase 2/3, open-label, repeat-dose study of the PK, efficacy, and safety of the
      IMP, in pediatric and adult subjects with hypoplasminogenemia. The study consists of a
      screening period and 3 treatment segments (Segment 1,2, and 3). Subjects who have documented
      individual PK profiles do not need to undergo Segment 1 and can proceed directly to Segment
      2. Subjects in Segment 1 will receive a single dose of 6.6 mg/kg IMP infusion. Blood samples
      for PK analysis will be drawn prior to infusion and subsequently through 96 hours after the
      infusion to establish individual PK profiles. The sample drawn prior to infusion will be used
      to measure the subject's baseline anti-plasminogen antibody, plasminogen activity and antigen
      as well as D-dimer levels. The resulting PK profile will be used to determine each subject's
      dosing interval in Segment 2.

      Based on individual PK profiles from Segment 1 subjects will receive 6.6 mg/kg IMP infusion
      every second, third, or fourth day for 12 weeks in Segment 2. For subjects who directly enter
      Segment 2, baseline assessments will be conducted before the first dose of IMP, including a
      blood sample to measure the baseline anti-plasminogen antibody, plasminogen activity and
      antigen as well as D-dimer levels. Subjects will visit the study sites on Week 1 and
      subsequently every 4 weeks, and receive the IMP infusion at the study site. Blood samples
      will be obtained at each study visit at Weeks 4, 8 and 12 and by a home health nurse at Weeks
      2, 6 and 10. Subjects will undergo clinical assessments of the disease, including but not
      limited to: photographic measurements of visible lesions, spirometry for subjects with
      pulmonary involvement, and imaging study of nonvisible lesions, as applicable. Plasma samples
      will be drawn before IMP administration every 2 weeks to measure the trough levels of
      plasminogen activity and antigen, and D-dimer.

      At the end of Segment 2, subjects will have the option to participate in Segment 3 where they
      will continue to receive IMP for an additional 36 weeks in Norway, and until product
      licensing or study termination by the sponsor for subjects in the United States. Subjects
      will return to the study sites for assessments every 3 months to monitor subjects' clinical
      status and plasminogen trough levels. Subjects at the Norway site in Segment 3 should return
      to the study site for a safety follow-up visit 30 days after the final IMP dose. Due to the
      delay in product approval, subjects at the US site in Segment 3 will be allowed to enroll in
      treatment protocol 2002C018G and continue ongoing IMP treatment without any break in
      treatment. If subjects decide to not enter treatment protocol 2002C018G, then they will stop
      IMP and return to the study site for a safety follow-up visit 30 days after the final IMP
      dose.

      The primary objective of this study is to achieve an increase of individual trough
      plasminogen activity by at least an absolute 10% (i.e., 10 U/dL) from baseline during the 12
      weeks of plasminogen replacement therapy in Segment 2; and to evaluate the efficacy of
      plasminogen replacement therapy on clinically evident or visible symptoms of
      hypoplasminogenemia during the 48 weeks of dosing in Segments 2 and 3.
    

Study Phase

Phase 2/Phase 3

Study Type

Interventional


Primary Outcome

Overall Clinical Success in Number and Size of Lesions as Measured by Photographic or Other Imaging Modality Depending on the Organ System Affected or Change in Affected Organ Functionality at 48 Weeks.

Secondary Outcome

 Overall Clinical Success in Number and Size of Lesions as Measured by Photographic or Other Imaging Modality Depending on the Organ System Affected or Change in Affected Organ Functionality at 12 Weeks

Condition

Hypoplasminogenemia

Intervention

Plasminogen (Human) intravenous

Study Arms / Comparison Groups

 6.6 mg/kg Plasminogen (Human) Intravenous
Description:  6.6 mg/kg Plasminogen (Human) Intravenous given every 2 to 4 days by a 10- to 30-minute intravenous infusion

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

15

Start Date

May 4, 2016

Completion Date

October 8, 2018

Primary Completion Date

December 17, 2017

Eligibility Criteria

        Inclusion Criteria:

          -  Subject is a male or female between the ages of 2 and 80 years (inclusive), is able to
             provide informed consent or assent, and agrees to use contraceptive methods during the
             study (unless documented as biologically or surgically sterile or has not reached
             reproductive age).

          -  Subject has documented history of hypoplasminogenemia and has plasminogen activity
             level ≤ 45%.

          -  Subject had a documented history of lesions and symptoms consistent with a diagnosis
             of congenital plasminogen deficiency.

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

        Exclusion Criteria:

          -  Subject has uncontrolled hypertension; clinical or laboratory evidence of an
             intercurrent infection; a malignancy within 3 years, except for basal or squamous cell
             skin cancer; a psychiatric disorder; chronic or acute clinically significant
             inter-current illness; or evidence of renal and hepatic dysfunction.

          -  Subject is pregnant or lactating

          -  Subject has a history of anaphylactic reactions to blood or blood products that may
             interfere with participation in study in the opinion of the investigator.

          -  Subject is a previous organ transplant recipient; has received exogenous plasminogen
             within 2 weeks of the screening; has a history of anaphylactic reactions to blood or
             blood products; or has received another IRB-approved interventional clinical trial of
             a drug, biologic, or device within 30 days before the first dose of the IMP.
      

Gender

All

Ages

2 Years - 80 Years

Accepts Healthy Volunteers

No

Contacts

Amy Shapiro, MD, , 

Location Countries

Norway

Location Countries

Norway

Administrative Informations


NCT ID

NCT02690714

Organization ID

2002C011G


Responsible Party

Sponsor

Study Sponsor

Prometic Biotherapeutics, Inc.


Study Sponsor

Amy Shapiro, MD, Principal Investigator, Indiana Hemophilia & Thrombosis Center


Verification Date

July 2021