A Phase 1 Study of ProMetic Plasminogen (Human) Intravenous in Adults and Children With Plasminogen Deficiency

NCT02312180 | Completed Phase 1 DMC

• 1 other identifier: 2002C005G
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief 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". 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.

Conditions

Type I Plasminogen Deficiency; Hypoplasminogenemia

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  8 months

Study Arms (2)

Cohort 1

EXPERIMENTAL

low dose group of 2 mg/kg Plasminogen (Human) Intravenous

Biological: Plasminogen (Human) Intravenous

Cohort 2

EXPERIMENTAL

mid-dose group of 6 mg/kg Plasminogen (Human) Intravenous

Biological: Plasminogen (Human) Intravenous

Interventions

Plasminogen (Human) Intravenous BIOLOGICAL

Plasma-derived purified plasminogen formulated for intravenous administration

Cohort 1; Cohort 2

Eligibility Criteria

• Age: 12 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Prometic Biotherapeutics, Inc.: lead

Study Sites (1)

Indiana Hemophilia and Thrombosis Center

Indianapolis, Indiana, 46260, United States

Location

MeSH Terms

Conditions

Plasminogen Deficiency, Type I; Congenital Plasminogen Deficiency

Interventions

Plasminogen

Intervention Hierarchy (Ancestors)

Enzyme Precursors; Enzymes and Coenzymes; Beta-Globulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins; Protein Precursors

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: December 4, 2014
• First Posted: December 9, 2014
• Study Start: December 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: February 1, 2016
• Last Updated: August 29, 2017

Record last verified: 2017-08

Locations

US (1)