A Study of Prometic Plasminogen IV Infusion in Subjects With Hypoplasminogenemia

NCT02690714 | Completed Phase 2 Results DMC

• 1 other identifier: 2002C011G
• Study Type: interventional
• Target: 15
• Locations: 2 countries
• Sites: 2

Brief Summary

This is a Phase 2/3 pivotal study to evaluate pharmacokinetics (PK), efficacy, and safety of Prometic Plasminogen (Human) Intravenous Lyophilized Solution, the investigational medicinal product (IMP), in pediatric and adult subjects with hypoplasminogenemia.

Conditions

Hypoplasminogenemia; Congenital Plasminogen Deficiency

Outcome Measures

Primary Outcomes (2)

• 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

Secondary Outcomes (14)

• 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

  12 Weeks

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

  12 weeks

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

  48 Weeks

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

  12 weeks

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

  48 weeks

Study Arms (1)

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

Biological: Plasminogen (Human) intravenous

Interventions

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.

6.6 mg/kg Plasminogen (Human) Intravenous

Eligibility Criteria

• Age: 2 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Prometic Biotherapeutics, Inc.: lead

Study Sites (2)

Indiana Hemophilia and Thrombosis Center

Indianapolis, Indiana, 46260, United States

Location

Oslo University Hospital HF

Oslo, Sognsvannvejen 20, 0372, Norway

Location

Related Publications (2)

• 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.

  PMID: 29321155 BACKGROUND

• 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.

  PMID: 37674358 DERIVED

MeSH Terms

Conditions

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

Results Point of Contact

• Title: Senior Director, Clinical Development
• Organization: Prometic Biotherapeutics Inc.

clinical@prometic.com

301-549-9761

Study Officials

• Amy Shapiro, MD

  Indiana Hemophilia & Thrombosis Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: February 12, 2016
• First Posted: February 24, 2016
• Study Start: May 4, 2016
• Primary Completion: December 17, 2017
• Study Completion: October 8, 2018
• Last Updated: August 2, 2021
• Results First Posted: April 19, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); NO (1)