Type I Plasminogen DeficiencyPhase 1NCT02312180
A Phase 1 Study of ProMetic Plasminogen (Human) Intravenous in Adults and Children With Plasminogen Deficiency
A Phase 1 study testing Plasminogen (Human) Intravenous in people with Type I Plasminogen Deficiency and Hypoplasminogenemia, run by Prometic Biotherapeutics, Inc. at 1 site in United States.
Trial 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". Read more about this study
- Who is it for?
- Ages 12 to 80 years
- Conditions the study is for
- Type I Plasminogen Deficiency, Hypoplasminogenemia
- 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
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2014to Feb 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 12 to 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Subject has provided informed consent/assent, or the subject's guardian has given consent if the subject is under 18 years
- Subject is male or female between 12 and 80 years of age, inclusive
- Subject has a diagnosis of hypoplasminogenemia evidenced by an abnormal, decreased plasminogen activity level, regardless of plasminogen antigen level
- Subject has a plasminogen activity level ≤ 40%
- 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
- 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
Who cannot join
- 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
- Subject has evidence of uncontrolled hypertension
- Subject has clinical or laboratory evidence of an intercurrent infection as evidenced by symptoms including fever, tachycardia, or other specific signs and symptoms*
- Subject is pregnant and/or lactating
- Subject has or has had a malignancy, except for basal and squamous cell skin cancer, within 3 years of Baseline
- Subject is a previous organ transplant recipient
Show all 14Show fewer
- Subject is receiving exogenous plasminogen (ocular or IV), including laboratory grade plasminogen and fresh lyophilized plasma within two weeks of Baseline
- 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
- Subject has experienced a severe adverse event in a prior cohort of this study.
- Subject has evidence of renal dysfunction, defined as serum creatinine of > 2 times the upper limit of normal
- 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)
- Subject has participated in another IRB-approved interventional clinical trial of a drug, biologic, or device within 30 days of Baseline
- 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
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Indiana Hemophilia and Thrombosis Center
Indianapolis, Indiana, 46260
About this study
Official title: A Phase 1, Dose Escalation, and Pharmacokinetic Study of ProMetic Plasminogen Administered as Intravenous Infusion in Adults and Children With Hypoplasminogenemia
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.
Read the 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.
- Conditions
- Type I Plasminogen Deficiency, Hypoplasminogenemia
- Being tested
- Plasminogen (Human) Intravenous
- Medical subject headings
- Plasminogen Deficiency, Type I, 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
Plasma-derived purified plasminogen formulated for intravenous administration
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | low dose group of 2 mg/kg Plasminogen (Human) Intravenous Receives: Biological: Plasminogen (Human) Intravenous |
| Cohort 2 | Experimental | mid-dose group of 6 mg/kg Plasminogen (Human) Intravenous Receives: Biological: Plasminogen (Human) Intravenous |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
The following PK parameters will be calculated from PLG activity and antigen levels using the non-compartmental PK analysis method: 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). Pharmacokinetic (PK) profile of lyophilized plasminogen (PLG) at 3 dose levels (the third dose is optional) in subjects with hypoplasminogenemia to determine the desirable dose and dosing interval to be studied in a Phase 2/3 study.
Measured: 8 months
Secondary outcomes (1)
To evaluate the safety and tolerability of PLG in subjects with hypoplasminogenemia, as measured by Rate, severity, and relatedness of any adverse events.
Rate, severity, and relatedness of any adverse events. Changes from baseline observed or reported in medical history, vital signs, physical exam, clinical laboratory tests. Assessment of development of antibodies against plasminogen.
Measured: 8 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2014 (estimated)
- Study startDec 2014
- Primary completionDec 2015
- Study completionFeb 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type I Plasminogen DeficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Prometic Biotherapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02312180
- Sponsor's protocol ID
- 2002C005G
- Status last verified
- Aug 2017
- First submitted
- 4 Dec 2014
- Last updated
- 29 Aug 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Expanded access
- Available
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Dose Escalation, and Pharmacokinetic Study of ProMetic Plasminogen Administered as Intravenous Infusion in Adults and Children With Hypoplasminogenemia
- ClinicalTrials.gov ID
- NCT02312180
- Acronym / sponsor ID
- 2002C005G
- Conditions
- Type I Plasminogen Deficiency, Hypoplasminogenemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Prometic Biotherapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- Dec 2014
- Primary completion
- Dec 2015 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 9 Dec 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Biological: Plasminogen (Human) Intravenouslow dose group of 2 mg/kg Plasminogen (Human) Intravenous |
| Cohort 2 | Experimental | Biological: Plasminogen (Human) Intravenousmid-dose group of 6 mg/kg Plasminogen (Human) Intravenous |
Who may qualify
- Ages
- 12 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Subject has provided informed consent/assent, or the subject's guardian has given consent if the subject is under 18 years
- Subject is male or female between 12 and 80 years of age, inclusive
- Subject has a diagnosis of hypoplasminogenemia evidenced by an abnormal, decreased plasminogen activity level, regardless of plasminogen antigen level
- Subject has a plasminogen activity level ≤ 40%
- 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
Key exclusion criteria (14 listed)
- 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
- Subject has evidence of uncontrolled hypertension
- Subject has clinical or laboratory evidence of an intercurrent infection as evidenced by symptoms including fever, tachycardia, or other specific signs and symptoms*
- Subject is pregnant and/or lactating
- Subject has or has had a malignancy, except for basal and squamous cell skin cancer, within 3 years of Baseline
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Plasminogen (Human) IntravenousPlasma-derived purified plasminogen formulated for intravenous administration | Biological | Cohort 1, Cohort 2 |
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).
Time frame: 8 months
The following PK parameters will be calculated from PLG activity and antigen levels using the non-compartmental PK analysis method: 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). Pharmacokinetic (PK) profile of lyophilized plasminogen (PLG) at 3 dose levels (the third dose is optional) in subjects with hypoplasminogenemia to determine the desirable dose and dosing interval to be studied in a Phase 2/3 study.
1 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.
Time frame: 8 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Plasminogen (Human) Intravenous in people with Type I Plasminogen Deficiency and Hypoplasminogenemia, run by Prometic Biotherapeutics, Inc. at 1 site in United States.
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 6 inclusion and 14 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 29 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
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). (time frame: 8 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 Aug 2017.