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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 6.6 mg/kg Plasminogen (Human) Intravenous | Experimental | 6.6 mg/kg Plasminogen (Human) Intravenous given every 2 to 4 days by a 10- to 30-minute intravenous infusion |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Plasminogen (Human) intravenous | Biological | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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". | 48 weeks |
| 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. | 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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". |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Amy Shapiro, MD | Indiana Hemophilia &Thrombosis Center, Inc. | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Indiana Hemophilia and Thrombosis Center | Indianapolis | Indiana | 46260 | United States | ||
| Oslo University Hospital HF |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29321155 | Background | 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. | |
| 42226455 | Derived |
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This study was conducted at 2 sites, 1 in the United States (US) and 1 in Norway. The first participant was screened in May 2016 and the last participant visit was in October 2018.
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| ID | Title | Description |
|---|---|---|
| FG000 | 6.6 mg/kg Plasminogen (Human) Intravenous | Prometic 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. Some subjects received more than 48 weeks of study drug. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Segment 1: Single-dose Day -4 to Day 0 |
| |||||||||||||
| Segment 2: Multi-dose Day 0 to Week 12 |
| |||||||||||||
| Segment 3: Extended Treatment Wks 12-48 |
| |||||||||||||
| Post-Wk 48: Safety Week 48 to EoS Visit |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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". | Efficacy Population Week 48-Segment 3 included all 15 enrolled participants who completed the Week 48 visit at the time of the data cut-off date of 14Dec2017. This analysis included 11 participants with 47 visible and/or non-visible lesions at baseline. All 15 participants were assessed, however only 11 participants had visible and/or non-visible lesions at baseline. | Posted | Count of Units | Lesions | 48 weeks | Lesions |
Safety was assessed during the treatment period (up to 124 weeks) and a 30-day post-treatment period.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study drug treatment.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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). 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ileus | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lymph node pain | Blood and lymphatic system disorders | MedDRA (19.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Director, Clinical Development | Prometic Biotherapeutics Inc. | 301-549-9761 | clinical@prometic.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 8, 2018 | Dec 21, 2020 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 1, 2017 | Dec 21, 2020 | SAP_001.pdf |
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| ID | Term |
|---|---|
| C580017 | Congenital Plasminogen Deficiency |
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| ID | Term |
|---|---|
| D010958 | Plasminogen |
| ID | Term |
|---|---|
| D004792 | Enzyme Precursors |
| D045762 | Enzymes and Coenzymes |
| D001609 | Beta-Globulins |
| D012712 | Serum Globulins |
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| 12 Weeks |
| 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). | 12 weeks |
| 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). | 48 Weeks |
| 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. | 12 weeks |
| 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. | 48 weeks |
| 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. | Week 2 to Week 120 |
| 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. | Week 2 to Week 120 |
| 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 | First dose and 12 weeks |
| 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. | First dose and 12 weeks |
| Cmax of Plasminogen Activity After First Dose and at Week 12 | Cmax is the maximum plasma concentration of Plasminogen | First dose and 12 weeks |
| Cl of Plasminogen Activity After First Dose and at Week 12 | Cl is the volume of plasma cleared of Plasminogen per unit time | First dose and 12 weeks |
| 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 | First dose and 12 weeks |
| 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 | First dose and 12 weeks |
| Vss for Plasminogen Activity After First Dose and at Week 12 | Vss is the apparent volume of distribution at steady state of Plasminogen | First dose and 12 weeks |
| Oslo |
| Sognsvannvejen 20 |
| 0372 |
| Norway |
| 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. |
| 37674358 | Derived | 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. |
|
| years |
|
| Age, Customized | Count of Participants | Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Weight | Mean | Standard Deviation | Kg |
|
| Visible and Non-Visible Lesions by Participant | Count of Participants | Participants |
|
| Number of Visible and Assesable Non-Visible Lesions | Number | Number of lesions |
|
| Plasminogen Activity | Plasminogen activity is a measurement of functional plasminogen levels. Plasminogen activity levels were measured with an automated chromogenic assay. Assay calibration curve was performed with a pool of normal human plasma with the assigned value of 100% plasminogen and plasminogen activity levels were reported in %. The normal reference range of plasminogen activity in healthy subjects was determined to be 70%-130% and the limit of quantification was set at 5% | Mean | Standard Deviation | % activity |
|
| Plasminogen Activity | See note above | Count of Participants | Participants |
|
| Plasminogen antigen | Mean | Standard Deviation | mg/dL |
|
| Plasminogen antigen | Count of Participants | Participants |
|
| Quality of Life Assessment | For the QOL assessment, participants were asked to rate their overall QOL using a 11-point scale (0 =non-functioning, 10 = normal; The QOL scale was adapted from a scale developed by the American Chronic Pain Association. | Count of Participants | Participants |
|
| Lesions |
|
|
|
| Primary | 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. | Pharmacokinetic Population included any participant who had completed Segment 2 dosing and had provided at least 3 blood samples to measure plasminogen activity trough levels. | Posted | Count of Participants | Participants | 12 weeks |
|
|
|
| Secondary | 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". | Efficacy population week 12 included all 15 enrolled participants who completed the week 12 visit. All 15 participants were assessed, however only 11 participants had visible and/or non-visible lesions at baseline. | Posted | Count of Units | Number of Lesions | 12 Weeks | Number of Lesions | Number of Lesions |
|
|
|
| Secondary | 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). | CGI-I population included all 15 enrolled participants who completed the week 12 (and week 48) visit. | Posted | Count of Participants | Participants | 12 weeks |
|
|
|
| Secondary | 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). | CGI-I population included all 15 enrolled participants who completed the week 48 (and week 12) visit. | Posted | Count of Participants | Participants | 48 Weeks |
|
|
|
| Secondary | 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. | Efficacy Population Week 48-Segment 3 included all 15 enrolled participants who completed the Week 48 visit at the time of the data cut-off date of 14Dec2017 | Posted | Count of Participants | Participants | 12 weeks |
|
|
|
| Secondary | 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. | Efficacy Population Week 48-Segment 3 included all 15 enrolled participants who completed the Week 48 visit at the time of the data cut-off date of 14Dec2017 | Posted | Count of Participants | Participants | 48 weeks |
|
|
|
| Secondary | 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. | Pharmacokinetic Population included any participant who had completed Segment 2, 3 and post week 48 dosing and had provided at least 3 blood samples to measure plasminogen activity trough levels. | Posted | Mean | Standard Deviation | percentage of activity | Week 2 to Week 120 |
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| Secondary | 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. | Pharmacokinetic Population included any participant who had completed Segment 2, 3 and post week 48 dosing and had provided at least 3 blood samples to measure plasminogen antigen trough levels. | Posted | Mean | Standard Deviation | mg/dL | Week 2 to Week 120 |
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|
|
| Secondary | 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 | Pharmacokinetic Population included any participant who had completed Segment 2 dosing and had provided at least 3 blood samples to measure plasminogen activity trough levels. | Posted | Mean | Standard Deviation | Hours | First dose and 12 weeks |
|
|
|
| Secondary | 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. | Pharmacokinetic Population included any participant who had completed Segment 2 dosing and had provided at least 3 blood samples to measure plasminogen activity trough levels. | Posted | Mean | Standard Deviation | hr*% | First dose and 12 weeks |
|
|
|
| Secondary | Cmax of Plasminogen Activity After First Dose and at Week 12 | Cmax is the maximum plasma concentration of Plasminogen | Pharmacokinetic Population included any participant who had completed Segment 2 dosing and had provided at least 3 blood samples to measure plasminogen activity trough levels. | Posted | Mean | Standard Deviation | % plasminogen activity | First dose and 12 weeks |
|
|
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| Secondary | Cl of Plasminogen Activity After First Dose and at Week 12 | Cl is the volume of plasma cleared of Plasminogen per unit time | Pharmacokinetic Population included any participant who had completed Segment 2 dosing and had provided at least 3 blood samples to measure plasminogen activity trough levels. | Posted | Mean | Standard Deviation | mL/hr/kg | First dose and 12 weeks |
|
|
|
| Secondary | 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 | Pharmacokinetic Population included any participant who had completed Segment 2 dosing and had provided at least 3 blood samples to measure plasminogen activity trough levels. | Posted | Mean | Standard Deviation | hr*% | First dose and 12 weeks |
|
|
|
| Secondary | 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 | Pharmacokinetic Population included any participant who had completed Segment 2 dosing and had provided at least 3 blood samples to measure plasminogen activity trough levels. | Posted | Mean | Standard Deviation | hours | First dose and 12 weeks |
|
|
|
| Secondary | Vss for Plasminogen Activity After First Dose and at Week 12 | Vss is the apparent volume of distribution at steady state of Plasminogen | Pharmacokinetic Population included any participant who had completed Segment 2 dosing and had provided at least 3 blood samples to measure plasminogen activity trough levels. | Posted | Mean | Standard Deviation | mL/kg | First dose and 12 weeks |
|
|
|
| 0 |
| 15 |
| 3 |
| 15 |
| 15 |
| 15 |
| Pneumonia | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
|
| Ear operation | Surgical and medical procedures | MedDRA (19.0) | Systematic Assessment |
|
| Ossiculoplasty | Surgical and medical procedures | MedDRA (19.0) | Systematic Assessment |
|
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA (19.0) | Systematic Assessment |
|
| Cardiac flutter | Cardiac disorders | MedDRA (19.0) | Systematic Assessment |
|
| Ehlers-Danlos syndrome | Congenital, familial and genetic disorders | MedDRA (19.0) | Systematic Assessment |
|
| Deafness unilateral | Ear and labyrinth disorders | MedDRA (19.0) | Systematic Assessment |
|
| Ear pain | Ear and labyrinth disorders | MedDRA (19.0) | Systematic Assessment |
|
| Excessive cerumen production | Ear and labyrinth disorders | MedDRA (19.0) | Systematic Assessment |
|
| Hypoacusis | Ear and labyrinth disorders | MedDRA (19.0) | Systematic Assessment |
|
| Motion sickness | Ear and labyrinth disorders | MedDRA (19.0) | Systematic Assessment |
|
| Tinnitus | Ear and labyrinth disorders | MedDRA (19.0) | Systematic Assessment |
|
| Tympanic membrane perforation | Ear and labyrinth disorders | MedDRA (19.0) | Systematic Assessment |
|
| Conjunctival deposit | Eye disorders | MedDRA (19.0) | Systematic Assessment |
|
| Eye discharge | Eye disorders | MedDRA (19.0) | Systematic Assessment |
|
| Eye inflammation | Eye disorders | MedDRA (19.0) | Systematic Assessment |
|
| Eye irritation | Eye disorders | MedDRA (19.0) | Systematic Assessment |
|
| Eye pain | Eye disorders | MedDRA (19.0) | Systematic Assessment |
|
| Eye swelling | Eye disorders | MedDRA (19.0) | Systematic Assessment |
|
| Ocular hyperaemia | Eye disorders | MedDRA (19.0) | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Abdominal pain lower | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Aphthous ulcer | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Colitis | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Crohn's disease | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Dental carries | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Gastric dilatation | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Gastroesophageal reflux disease | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Gingival bleeding | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Haematochezia | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Haemorrhoids | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Hypoaesthesia oral | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Mouth ulceration | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Paraesthesia oral | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Proctalgia | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Tooth development disorder | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA (19.0) | Systematic Assessment |
|
| Chest discomfort | General disorders | MedDRA (19.0) | Systematic Assessment |
|
| Chills | General disorders | MedDRA (19.0) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (19.0) | Systematic Assessment |
|
| Feeling abnormal | General disorders | MedDRA (19.0) | Systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA (19.0) | Systematic Assessment |
|
| Infusion site bruising | General disorders | MedDRA (19.0) | Systematic Assessment |
|
| Infusion site discomfort | General disorders | MedDRA (19.0) | Systematic Assessment |
|
| Infusion site erythema † | General disorders | MedDRA (19.0) | Systematic Assessment |
|
| Infusion site extravasation | General disorders | MedDRA (19.0) | Systematic Assessment |
|
| Infusion site pain | General disorders | MedDRA (19.0) | Systematic Assessment |
|
| Infusion site rash | General disorders | MedDRA (19.0) | Systematic Assessment |
|
| Infusion site swelling | General disorders | MedDRA (19.0) | Systematic Assessment |
|
| Pain | General disorders | MedDRA (19.0) | Systematic Assessment |
|
| Peripheral swelling | General disorders | MedDRA (19.0) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (19.0) | Systematic Assessment |
|
| Seasonal allergies | Immune system disorders | MedDRA (19.0) | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
|
| Conjunctivitis | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
|
| Cystitis | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
|
| Ear infection | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
|
| Fungal infection | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
|
| Gastroenteritis norovirus | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
|
| H1N1 influenza | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
|
| Hordeolum | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
|
| Lower respiratory tract infection | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
|
| Pharyngitis streptococcal | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
|
| Tonsilitis | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
|
| Tooth infection | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
|
| Viral upper respiratory tract infection | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
|
| Animal bite | Injury, poisoning and procedural complications | MedDRA (19.0) | Systematic Assessment |
|
| Arthropod sting | Injury, poisoning and procedural complications | MedDRA (19.0) | Systematic Assessment |
|
| Chest injury | Injury, poisoning and procedural complications | MedDRA (19.0) | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA (19.0) | Systematic Assessment |
|
| Joint injury | Injury, poisoning and procedural complications | MedDRA (19.0) | Systematic Assessment |
|
| Procedural nausea | Injury, poisoning and procedural complications | MedDRA (19.0) | Systematic Assessment |
|
| Procedural pain | Injury, poisoning and procedural complications | MedDRA (19.0) | Systematic Assessment |
|
| Procedural vomiting | Injury, poisoning and procedural complications | MedDRA (19.0) | Systematic Assessment |
|
| Road traffic accident | Injury, poisoning and procedural complications | MedDRA (19.0) | Systematic Assessment |
|
| Scratch | Injury, poisoning and procedural complications | MedDRA (19.0) | Systematic Assessment |
|
| Skin abrasion | Injury, poisoning and procedural complications | MedDRA (19.0) | Systematic Assessment |
|
| Tongue injury | Injury, poisoning and procedural complications | MedDRA (19.0) | Systematic Assessment |
|
| Wound | Injury, poisoning and procedural complications | MedDRA (19.0) | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA (19.0) | Systematic Assessment |
|
| Blood iron decrease | Investigations | MedDRA (19.0) | Systematic Assessment |
|
| Blood pressure systolic increased | Investigations | MedDRA (19.0) | Systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA (19.0) | Systematic Assessment |
|
| Progesterone decreased | Investigations | MedDRA (19.0) | Systematic Assessment |
|
| Diabetes mellitus | Metabolism and nutrition disorders | MedDRA (19.0) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Systematic Assessment |
|
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Systematic Assessment |
|
| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Systematic Assessment |
|
| Limb discomfort | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Systematic Assessment |
|
| Cholesteatoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (19.0) | Systematic Assessment |
|
| Skin papilloma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (19.0) | Systematic Assessment |
|
| Burning sensation | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
|
| Migraine | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
|
| Post-traumatic headache | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA (19.0) | Systematic Assessment |
|
| Mood altered | Psychiatric disorders | MedDRA (19.0) | Systematic Assessment |
|
| Panic attack | Psychiatric disorders | MedDRA (19.0) | Systematic Assessment |
|
| Restlessness | Psychiatric disorders | MedDRA (19.0) | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA (19.0) | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA (19.0) | Systematic Assessment |
|
| Micturition urgency | Renal and urinary disorders | MedDRA (19.0) | Systematic Assessment |
|
| Renal pain | Renal and urinary disorders | MedDRA (19.0) | Systematic Assessment |
|
| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA (19.0) | Systematic Assessment |
|
| Ovulation pain | Reproductive system and breast disorders | MedDRA (19.0) | Systematic Assessment |
|
| Pelvic pain | Reproductive system and breast disorders | MedDRA (19.0) | Systematic Assessment |
|
| Uterine pain | Reproductive system and breast disorders | MedDRA (19.0) | Systematic Assessment |
|
| Vaginal haemorrhage | Reproductive system and breast disorders | MedDRA (19.0) | Systematic Assessment |
|
| Vulvovaginal pain | Reproductive system and breast disorders | MedDRA (19.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Diaphragmatic disorder | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Nasal discomfort | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Nasal oedema | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Oropahryngeal discomfort | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Paranasal sinus discomfort | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Sinus congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Sputum increased | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Throat irritation | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Tonsillar hypertrophy | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Systematic Assessment |
|
| Petechiae | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Systematic Assessment |
|
| Pruritis | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Systematic Assessment |
|
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Systematic Assessment |
|
| Skin exfoliation | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Systematic Assessment |
|
| Swelling face | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Systematic Assessment |
|
| Tumour pruritis | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Systematic Assessment |
|
| Artificial crown procedure | Surgical and medical procedures | MedDRA (19.0) | Systematic Assessment |
|
| Central venous catheter removal | Surgical and medical procedures | MedDRA (19.0) | Systematic Assessment |
|
| Tooth repair | Surgical and medical procedures | MedDRA (19.0) | Systematic Assessment |
|
| Venipuncture | Surgical and medical procedures | MedDRA (19.0) | Systematic Assessment |
|
| Wisdom teeth removal | Surgical and medical procedures | MedDRA (19.0) | Systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA (19.0) | Systematic Assessment |
|
| Haematoma | Vascular disorders | MedDRA (19.0) | Systematic Assessment |
|
| Haemorrhage | Vascular disorders | MedDRA (19.0) | Systematic Assessment |
|
| Dystension | Vascular disorders | MedDRA (19.0) | Systematic Assessment |
|
| Urinary tract pain | Renal and urinary disorders | MedDRA (19.0) | Systematic Assessment |
|
Publication of data generated in the study is governed by the Investigator Clinical Trial Agreement
| D001798 |
| Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D005916 | Globulins |
| D011498 | Protein Precursors |
| Title | Measurements |
|---|---|
|
| Not applicable/Not assessed |
|
| CGI score 3 = Minimally improved : Week 12 |
|
| CGI score 4= No change : Week 12 |
|
| CGI score 5 = Minimally worse : Week 12 |
|
| CGI score 6 = Much worse : Week 12 |
|
| CGI score 7 = Very much worse : Week 12 |
|
| CGI Score 3= Minimally improved: Week 48 |
|
| CGI Score 4= No change: Week 48 |
|
| CGI Score 5= Minimally worse: Week 48 |
|
| CGI Score 6= Much worse: Week 48 |
|
| CGI Score 7= Very much worse: Week 48 |
|
| QOL score = 3 : Week 12 |
|
| QOL score = 4 : Week 12 |
|
| QOL score = 5 : Week 12 |
|
| QOL score = 6 : Week 12 |
|
| QOL score = 7 : Week 12 |
|
| QOL score = 8 : Week 12 |
|
| QOL score = 9 : Week 12 |
|
| QOL score = 10 : Week 12 |
|
| QOL Score 3: Week 48 |
|
| QOL Score 4: Week 48 |
|
| QOL Score 5: Week 48 |
|
| QOL Score 6: Week 48 |
|
| QOL Score 7: Week 48 |
|
| QOL Score 8: Week 48 |
|
| QOL Score 9: Week 48 |
|
| QOL Score 10: Week 48 |
|
|
| Week 6 |
|
|
| Week 8 |
|
|
| Week 10 |
|
|
| Week 12 |
|
|
| Week 24 |
|
|
| Week 36 |
|
|
| Week 48 |
|
|
| Week 60 |
|
|
| Week 72 |
|
|
| Week 84 |
|
|
| Week 96 |
|
|
| Week 108 |
|
|
| Week 120 |
|
|
|
| Week 6 |
|
|
| Week 8 |
|
|
| Week 10 |
|
|
| Week 12 |
|
|
| Week 24 |
|
|
| Week 36 |
|
|
| Week 48 |
|
|
| Week 60 |
|
|
| Week 72 |
|
|
| Week 84 |
|
|
| Week 96 |
|
|
| Week 108 |
|
|
| Week 120 |
|
|