Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Prometic Plasminogen IV Infusion in Subjects With Hypoplasminogenemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02690714
Recruitment Status : Completed
First Posted : February 24, 2016
Last Update Posted : December 10, 2019
Sponsor:
Information provided by (Responsible Party):
Prometic Biotherapeutics, Inc.

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.

Condition or disease Intervention/treatment Phase
Hypoplasminogenemia Biological: Plasminogen (Human) intravenous Phase 2 Phase 3

Expanded Access : An investigational treatment associated with this study is no longer available outside the clinical trial.   More info ...

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : May 4, 2016
Actual Primary Completion Date : December 17, 2017
Actual Study Completion Date : October 8, 2018


Arm Intervention/treatment
Experimental: 6.6 mg/kg Plasminogen (Human) Intravenous
6.6 mg/kg Plasminogen (Human) Intravenous given every 2 to 4 days by a 10- to 30-minute intravenous infusion for 48 weeks (Norway) and longer until product licensing or study termination by the Sponsor (US).
Biological: Plasminogen (Human) intravenous
Prometic Plasminogen (Human) intravenous infusion given as single dose of 6.6 mg/kg in Segment 1 and repeat doses in Segments 2 and 3.




Primary Outcome Measures :
  1. Trough plasminogen activity levels during 12 weeks of study drug treatment [ Time Frame: 12 weeks ]
    Blood samples are collected before the first dose of the study drug to establish the baseline levels and every 2 weeks thereafter prior to study drug administration through Week 12 to measure trough levels of plasminogen activity.

  2. Number of lesions after 48 weeks of study drug treatment [ Time Frame: 48 weeks ]
    Clinical success is defined as 50% of subjects with visible or other measureable lesions achieving at least a 50% improvement in lesion number/size or functionality impact from baseline.

  3. Size of lesions after 48 weeks of study drug treatment [ Time Frame: 48 weeks ]
    Clinical success is defined as 50% of subjects with visible or other measurable lesions achieving at least a 50% improvement in lesion size from baseline.

  4. Spirometry results after 48 weeks of study drug treatment in subjects with bronchial lesions of hypoplasminogenemia. [ Time Frame: 48 weeks ]
    Clinical success is defined as 50% of subjects with visible or other measurable lesions achieving at least a 50% improvement in affected organ functionality (e.g., spirometry) from baseline.


Secondary Outcome Measures :
  1. Incidence of treatment emergent adverse events (TEAEs) [ Time Frame: Approximately 53 weeks ]
    • The relatedness and severity of all TEAEs will be summarized
    • Numbers of subjects who had changes from baseline in viral tests will be summarized
    • Number of subjects who had changes from baseline in immunogenicity tests will be summarized

  2. Trough plasminogen activity levels after 24, 36, and 48 weeks of study drug treatment [ Time Frame: 24-48 weeks ]
    Blood samples are collected before the first dose of the study drug to establish the baseline levels and at 24, 36, and 48 weeks thereafter prior to study drug administration to measure trough levels of plasminogen activity.

  3. Number of lesions after 12 weeks of study drug treatment [ Time Frame: 12 weeks ]
    Clinical success is defined as 50% of subjects with visible or other measurable lesions achieving at least a 50% improvement in lesion number from baseline.

  4. Size of lesions after 12 weeks of study drug treatment [ Time Frame: 12 weeks ]
    Clinical success is defined as 50% of subjects with visible or other measurable lesions achieving at least a 50% improvement in lesion size from baseline.

  5. Change from baseline in spirometry after 12 weeks of study drug treatment [ Time Frame: 12 weeks ]
    Clinical success is defined as 50% of subjects with visible or other measurable lesions achieving at least a 50% improvement in affected organ functionality (e.g., spirometry) from baseline.

  6. Clinical Global Impression-Global Improvement (CGI-I) scores after 12 and 48 weeks of study drug treatment [ Time Frame: 12 and 48 weeks ]
    CGI-I scores are measured at baseline and at 12 and 48 weeks after study drug treatment.

  7. Quality of life score after 12 and 48 weeks of study treatment [ Time Frame: 12 and 48 weeks ]
    Quality of life scores are measured at baseline and at 12 and 48 weeks after study drug treatment.

  8. Mean baseline-adjusted mean plasminogen activity levels after the first and Week 12 dose of study drug treatment [ Time Frame: 12 weeks ]
    Blood samples are collected prior to the first and Week 12 dose and at 0.167, 6, 24, 48, 72, and 96 hours after the first and Week 12 dose of study drug to measure plasminogen activity.

  9. Mean area under the concentration-time curve, from time 0 to the last measured time point (AUCLAST) of baseline-adjusted plasminogen activity after the first and Week 12 dose of study drug treatment [ Time Frame: 12 weeks ]
    To determine the mean AUCLAST of baseline-adjusted plasminogen activity in subjects with hypoplasminogenemia

  10. Mean extrapolated area under the concentration-time curve, from time 0 to infinity (AUCINF) of baseline-adjusted plasminogen activity after the first and Week 12 dose of study drug treatment [ Time Frame: 12 weeks ]
    To determine the mean AUCINF of baseline-adjusted plasminogen activity in subjects with hypoplasminogenemia

  11. Mean clearance (CL) of baseline-adjusted plasminogen activity after the first and Week 12 dose of study drug treatment [ Time Frame: 12 weeks ]
    To determine the mean CL of baseline-adjusted plasminogen activity in subjects with hypoplasminogenemia

  12. Mean MRT of baseline-adjusted plasminogen activity after the first and Week 12 dose of study drug treatment [ Time Frame: 12 weeks ]
    To determine the mean MRT of baseline-adjusted plasminogen activity in subjects with hypoplasminogenemia

  13. Mean Vd of baseline-adjusted plasminogen activity after the first and Week 12 dose of study drug treatment [ Time Frame: 12 weeks ]
    To determine the mean Vd of baseline-adjusted plasminogen activity in subjects with hypoplasminogenemia

  14. Mean terminal half-life (t1/2) of baseline-adjusted plasminogen activity after the first and Week 12 dose of study drug treatment [ Time Frame: 12 weeks ]
    To determine the mean t1/2 of baseline-adjusted plasminogen activity in subjects with hypoplasminogenemia

  15. Mean Cmax of baseline-adjusted plasminogen activity after the first and Week 12 dose of study drug treatment [ Time Frame: 12 weeks ]
    To determine the mean t1/2 of baseline-adjusted plasminogen activity in subjects with hypoplasminogenemia

  16. Mean baseline-adjusted mean plasminogen antigen levels after the first and Week 12 dose of study drug treatment [ Time Frame: 12 weeks ]
    Blood samples are collected prior to the first and Week 12 dose and at 0.167, 6, 24, 48, 72, and 96 hours after the first and Week 12 dose of study drug to measure plasminogen antigen levels.

  17. Mean AUCLAST of baseline-adjusted plasminogen antigen after the first and Week 12 dose of study drug treatment [ Time Frame: 12 weeks ]
    To determine the mean AUCLAST of baseline-adjusted plasminogen antigen in subjects with hypoplasminogenemia

  18. Mean AUCINF of baseline-adjusted plasminogen antigen after the first and Week 12 dose of study drug treatment [ Time Frame: 12 weeks ]
    To determine the mean AUCINF of baseline-adjusted plasminogen antigen in subjects with hypoplasminogenemia

  19. Mean CL of baseline-adjusted plasminogen antigen after the first and Week 12 dose of study drug treatment [ Time Frame: 12 weeks ]
    To determine the mean CL of baseline-adjusted plasminogen antigen in subjects with hypoplasminogenemia

  20. Mean MRT of baseline-adjusted plasminogen antigen after the first and Week 12 dose of study drug treatment [ Time Frame: 12 weeks ]
    To determine the mean MRT of baseline-adjusted plasminogen antigen in subjects with hypoplasminogenemia

  21. Mean Vd of baseline-adjusted plasminogen antigen after the first and Week 12 dose of study drug treatment [ Time Frame: 12 weeks ]
    To determine the mean Vd of baseline-adjusted plasminogen antigen in subjects with hypoplasminogenemia

  22. Mean t1/2 of baseline-adjusted plasminogen antigen after the first and Week 12 dose of study drug treatment [ Time Frame: 12 weeks ]
    To determine the mean t1/2 of baseline-adjusted plasminogen antigen in subjects with hypoplasminogenemia

  23. Mean Cmax of baseline-adjusted plasminogen antigen after the first and Week 12 dose of study drug treatment [ Time Frame: 12 weeks ]
    To determine the mean t1/2 of baseline-adjusted plasminogen antigen in subjects with hypoplasminogenemia

  24. Abnormal D-dimer levels after study drug treatment [ Time Frame: 48 weeks ]
    Abnormal D-dimer levels in subjects with hypoplasminogenemia



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   2 Years to 80 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02690714


Locations
Layout table for location information
United States, Indiana
Indiana Hemophilia and Thrombosis Center
Indianapolis, Indiana, United States, 46260
Norway
Oslo University Hospital HF
Oslo, Sognsvannvejen 20, Norway, 0372
Sponsors and Collaborators
Prometic Biotherapeutics, Inc.
Investigators
Layout table for investigator information
Principal Investigator: Amy Shapiro, MD Indiana Hemophilia & Thrombosis Center

Publications:
Layout table for additonal information
Responsible Party: Prometic Biotherapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02690714    
Other Study ID Numbers: 2002C011G
First Posted: February 24, 2016    Key Record Dates
Last Update Posted: December 10, 2019
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Coagulation Protein Disorders
Blood Coagulation Disorders
Hematologic Diseases
Plasminogen
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action