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HypoplasminogenemiaPhase 2/3NCT02690714

A Study of Prometic Plasminogen IV Infusion in Subjects With Hypoplasminogenemia

A Phase 2/3 study testing Plasminogen (Human) intravenous in people with Hypoplasminogenemia and Congenital Plasminogen Deficiency, run by Prometic Biotherapeutics, Inc. at 2 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 2 to 80 years
What is being tested?
Plasminogen (Human) intravenous
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
2 sitesin 2 countries
Study dates
4 May 2016to 8 Oct 2018
Phase
Phase 2/3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 2 to 80 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

United States1 site
  • Indiana Hemophilia and Thrombosis Center

    Indianapolis, Indiana, 46260

Other trials in United States

Norway1 site
  • Oslo University Hospital HF

    Oslo, Sognsvannvejen 20, 0372

Other trials in Norway

About this study

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

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.

Read the 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.

Being tested
Plasminogen (Human) intravenous
Medical subject headings
Congenital Plasminogen Deficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Plasminogen (Human) intravenousBiological

    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.

Study groups in NCT02690714
Study groupRoleWhat they receive
6.6 mg/kg Plasminogen (Human) IntravenousExperimental6.6 mg/kg Plasminogen (Human) Intravenous given every 2 to 4 days by a 10- to 30-minute intravenous infusion
Receives: Biological: Plasminogen (Human) intravenous

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Overall clinical success was defined as 50% of participants with visible or other measurable lesions achieving at least a 50% improvement in lesion number/size or functionality impact from baseline. Visible lesions were defined as lesions that could be imaged and analyzed with digital photography. Non-visible lesions were defined as lesions whose dimensions could have been assessed by medical imaging studies (eg, computed tomography, magnetic resonance imaging, ultrasound, etc) or functional assessments (eg, spirometry, audiogram, oximetry, etc).Visible lesions that had both a length and width as measured by the 1mm scale, were referred to as "measurable lesions", and visible lesions that were too small to measure by the 1mm scale (length and/or width could not have been measured) were referred to as "non-measurable lesions".

    Measured: 48 weeks

  2. Number and Percentage of Particpants Who Achieved the Target Plasminogen Activity Trough Levels for at Least 3 Measurements in 12 Weeks During Segment 2

    Plasminogen activity is a measurement of functional plasminogen levels and is therefore the most accurate and specific method to quantify active Plasminogen (Human) Intravenous concentration in participants' plasma. Primary endpoint success was defined as at least 80% of evaluable participants (ie, 8 or more) achieving the target trough levels for at least 3 measurements in 12 weeks. The target trough level was defined as an increase in plasminogen activity level of at least an absolute 10% (10 U/dL) from the participant's individual baseline level.

    Measured: 12 weeks

Secondary outcomes (14)
  1. 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

    Overall clinical success was defined as 50% of participants with visible or other measurable lesions achieving at least a 50% improvement in lesion number/size or functionality impact from baseline. Visible lesions were defined as lesions that could be imaged and analyzed with digital photography. Non-visible lesions were defined as lesions whose dimensions could have been assessed by medical imaging studies (eg, computed tomography, magnetic resonance imaging, ultrasound, etc) or functional assessments (eg, spirometry, audiogram, oximetry, etc).Visible lesions that had both a length and width as measured by the 1mm scale, were referred to as "measurable lesions", and visible lesions that were too small to measure by the 1mm scale (length and/or width could not have been measured) were referred to as "non-measurable lesions".

    Measured: 12 Weeks

  2. Clinical Global Impression-Global Improvement (CGI-I) Scores at Week 12

    CGI-I scores are measured at 12 and 48 weeks after study drug treatment. The CGI-I Scale is a single, clinician completed scale designed to capture the clinician's impression of the participant's disease improvement over time.

    For this scale, clinicians were asked to consider their experience in this population and rate the change relative to the participant's state at Baseline using a 7-point scale (1 = very much improved, 7 = very much worse).

    Measured: 12 weeks

  3. Clinical Global Impression-Global Improvement (CGI-I) Scores at Week 48

    CGI-I scores are measured at 12 and 48 weeks after study drug treatment. The CGI-I Scale is a single, clinician completed scale designed to capture the clinician's impression of the participant's disease improvement over time.

    For this scale, clinicians were asked to consider their experience in this population and rate the change relative to the participant's state at Baseline using a 7-point scale (1 = very much improved, 7 = very much worse).

    Measured: 48 Weeks

  4. Number of Participants With Improved Quality of Life (QOL) Score After 12 Weeks of Study Treatment

    Quality of life score (QOL) was measured at baseline and at 12 and 48 weeks after study drug treatment. For the QOL assessment, participants were asked to rate their overall QOL using an 11-point scale (0 = non-functioning, 10 = normal; The QOL scale was adapted from a scale developed by the American Chronic Pain Association.

    Measured: 12 weeks

  5. Number of Participants With Improved Quality of Life (QOL) Score After 48 Weeks of Study Treatment

    Quality of life score (QOL) was measured at baseline and at 12 and 48 weeks after study drug treatment. For the QOL assessment, participants were asked to rate their overall QOL using an 11-point scale (0 = non-functioning, 10 = normal; The QOL scale was adapted from a scale developed by the American Chronic Pain Association.

    Measured: 48 weeks

  6. Plasminogen Activity Trough Levels Between Week 2 and Week 120

    Plasminogen activity trough levels were measured at Weeks 2, 4, 6, 8, 10, 12, 24, 36, 48, 60, 72, 84, 96, 108, and 120.

    Measured: Week 2 to Week 120

  7. Plasminogen Antigen Trough Levels Between Week 2 and Week 120

    Plasminogen antigen trough levels were measured at Weeks 2, 4, 6, 8, 10, 12, 24, 36, 48, 60, 72, 84, 96, 108, and 120.

    Measured: Week 2 to Week 120

  8. Half-life (t1/2) of Plasminogen Activity After First Dose and at Week 12

    t1/2 is time required for the plasma concentration of Plasminogen to decrease 50% in the final stage of its elimination

    Measured: First dose and 12 weeks

  9. AUClast of Plasminogen Activity After the First Dose and at Week 12

    AUCLast is the area under the plasma concentration-curve of Plasminogen from time 0 to the last measured concentration.

    Measured: First dose and 12 weeks

  10. Cmax of Plasminogen Activity After First Dose and at Week 12

    Cmax is the maximum plasma concentration of Plasminogen

    Measured: First dose and 12 weeks

  11. Cl of Plasminogen Activity After First Dose and at Week 12

    Cl is the volume of plasma cleared of Plasminogen per unit time

    Measured: First dose and 12 weeks

  12. AUCinf of Plasminogen Activity After First Dose and at Week 12

    AUCinf is the area under the plasma concentration-curve of Plasminogen from time 0 extrapolated to infinity

    Measured: First dose and 12 weeks

  13. MRTlast for Plasminogen Activity After First Dose and at Week 12

    MRTLast is the mean residence time of Plasminogen from time 0 to the last measured concentration

    Measured: First dose and 12 weeks

  14. Vss for Plasminogen Activity After First Dose and at Week 12

    Vss is the apparent volume of distribution at steady state of Plasminogen

    Measured: First dose and 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Feb 2016 (estimated)
  2. Study start4 May 2016
  3. Primary completion17 Dec 2017
  4. Study completion8 Oct 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02690714
Sponsor's protocol ID
2002C011G
Status last verified
Jul 2021
First submitted
12 Feb 2016
Last updated
2 Aug 2021
Data monitoring committee
Yes
Individual data sharing
No
Expanded access
Available

Publications

  • Shapiro AD, Nakar C, Parker JM, Albert GR, Moran JE, Thibaudeau K, Thukral N, Hardesty BM, Laurin P, Sandset PM. Plasminogen replacement therapy for the treatment of children and adults with congenital plasminogen deficiency. Blood. 2018 Mar 22;131(12):1301-1310. doi: 10.1182/blood-2017-09-806729. Epub 2018 Jan 10.

    PubMed 29321155
  • Nakar C, Thibaudeau K, Mathias M, McDaniel H, Reschke M, Tenbrock K, Parker JM, Shapiro A. Sustained Therapeutic Efficacy of Intravenous Plasminogen Concentrate in Pediatric Patients With Type 1 Plasminogen Deficiency: An Analysis of Dosing Parameters and Clinical Outcomes. Pediatr Blood Cancer. 2026 Sep;73(9):e70454. doi: 10.1002/1545-5017.70454. Epub 2026 Jul 29.

    PubMed 42528055
  • Shapiro AD, Nakar C, Parker JM, Thibaudeau K, Crea R, Sandset PM. Plain language summary: a phase 2/3 study of plasminogen, human-tvmh for the treatment of children and adults with type 1 plasminogen deficiency. Expert Rev Hematol. 2026 Jul;19(7):669-680. doi: 10.1080/17474086.2026.2678346. Epub 2026 Jun 1.

    PubMed 42226455
  • Shapiro AD, Nakar C, Parker JM, Thibaudeau K, Crea R, Sandset PM. Plasminogen, human-tvmh for the treatment of children and adults with plasminogen deficiency type 1. Haemophilia. 2023 Nov;29(6):1556-1564. doi: 10.1111/hae.14849. Epub 2023 Sep 6.

    PubMed 37674358

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Plasminogen (Human) intravenous in people with Hypoplasminogenemia and Congenital Plasminogen Deficiency, run by Prometic Biotherapeutics, Inc. at 2 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States, Norway. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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. (time frame: 48 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02690714, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Aug 2021.

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