Tympanic Membrane Perforation MedDRA version: 20.0 Level: PT Classification code 10045210 Term: Tympanic membrane perforation System Organ Class: 10013993 - Ear and labyrinth disorders
Conditions
Sponsors
Prometic Biotherapeutics Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Male or female aged 18-70 years (both inclusive) 2) Subject has signed informed consent 3) Diagnosed with dry TMP that has been present for at least 6 months 4) TMP occupies 15-30% (both inclusive) of the surface area of the tympanic membrane at screening; if a subject has a TMP in both ears that meets all inclusion criteria, then the TMP associated with the worst hearing will be included in the study 5) Female subjects of childbearing potential must have a negative urine pregnancy test at screening. Female subjects of childbearing potential who are sexually active with a non sterile male partner must agree to use adequate birth control from the time of screening until 4 weeks after the last study drug administration. If a male subject has not been vasectomized at least 6 months before screening and partners with a woman of childbearing potential, he must be willing to use an acceptable contraceptive method from the time of screening until 4 weeks after the last study drug administration. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 29 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: 1) History of hypersensitivity reaction to blood products, plasma-derived products, local anesthesia, or aprotinin 2) Treatment with exogenous plasminogen (such as fresh frozen plasma) or a fibrinolytic agent (such as recombinant tissue plasminogen activator or streptokinase) during the 2 weeks prior to screening 3) Treatment with anti-inflammatory agents (including Non-Steroidal Anti-Inflammatory Drugs [NSAIDs]), immunosuppressive drugs (including any form of steroids or chemotherapy), growth factors, or anti-fibrinolytics (tranexamic acid, epsilon aminocaproic acid, or aprotinin) during the 2 weeks prior to screening 4) Treatment of any infection with systemic antimicrobial agents (antibiotics, antivirals, antifungals) during the 2 weeks prior to screening 5) Sensorineural hearing loss (SNHL) >35 dB in the affected ear, measured no more than 14 days before first dose of study drug 6) Recurrent or chronic bacterial infection in the affected ear during the 4 weeks prior to screening 7) Prior middle ear surgery in the affected ear (except tympanostomy) 8) History of malignancy treated in past 3 years (except for basal or squamous cell skin cancer) 9) Creatinine >2x the upper limit of normal (ULN); aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase (ALP) >3x ULN 10) History of diabetes 11) History of immunodeficiency disease 12) Other significant medical condition that the Investigator determines could interfere with compliance or study assessments (such as: recurrent or chronic infection, dementia, substance abuse, serious or unstable chronic organ disease) 13) If female: pregnant or lactating 14) Has participated in another investigational drug or medical device study for any medical condition during the 4 weeks prior to screening
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety and tolerability of 5 mg and 10 mg Plasminogen (Human) 10 injected subcutaneously (SC) near the tympanic membrane in adult subjects with chronic tympanic membrane perforation (TMP).;Secondary Objective: • To assess the feasibility of injecting 3 doses of SC Plasminogen (Human) 10 in 1 week at 2 dose levels (5 mg and 10 mg) near the tympanic membrane in this subject population. • To assess the efficacy of SC Plasminogen (Human) 10 at 2 dose levels (5 mg and 10 mg) on the healing of chronic TMP. • To assess the effect of SC Plasminogen (Human) 10 at 2 dose levels (5 mg and 10 mg) on ear discomfort in this study population. • To determine whether excision of the perforation rim affects the efficacy of SC Plasminogen (Human) 10 in this subject population.;Primary end point(s): Number, type, severity, and causality of treatment emergent adverse events (TEAEs) by treatment ;Timepoint(s) of evaluation of this end point: Visit 6 (3-month Follow-up, i.e. End-of-Study) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Proportion of injections that are technically feasible by treatment, defined as the ability to insert needle SC in the ear canal =5 mm from the tympanic annulus and deliver entire volume of IMP or placebo SC without spillage • Proportion of subjects with =50% reduction in the percentage of tympanic membrane surface area (TMSA) occupied by the TMP at 1 month compared with baseline by treatment • Proportion of subjects with TMP closure at 1 month compared with baseline by treatment, defined as the absence of visible perforation by otomicroscopy AND the presence of tympanic membrane movement with pneumatic pressure change in the ear canal • Proportion of subjects with >50% reduction in the percentage of TMSA occupied by the TMP at 3 months compared with baseline by treatment • Proportion of subjects with TMP closure at 3 months compared with baseline by treatment defined as the absence of visible perforation by otomicroscopy AND the presence of tympanic membrane movement with pneumatic pressure change in the ear canal • Change in VAS score for ear discomfort (pain or other unpleasant sensation) at 1 month compared with baseline by treatment • Change in VAS score for ear discomfort at 3 months compared with baseline by treatment ;Timepoint(s) of evaluation of this end point: Secondary endpoint 1: Visit 2, Visit 3, and Visit 4 Secondary endpoints 2, 3, and 6: Visit 5 (1-month Follow-up) Secondary endpoints 4, 5, and 7: Visit 6 (3-month Follow-up, i.e. End-of-Study) | — |
Countries
Sweden
Contacts
Public ContactRegulatory Affairs
Prometic Biotherapeutic Ltd
Outcome results
None listed