Regenerative Therapy for Soft Tissue Defects of the External Auditory Meatus with NPC-18

JRCT ID: jRCT2051230028

Registered date:26/05/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Subject has soft tissue defect of external auditory meatus resulting from injury or postoperative da
• Date of first enrollment: 01/05/2023
• Target sample size: 20
• Study type: Interventional

Intervention(s)

The soft tissue of the EAM was fully anesthetized
by applying a cotton ball soaked in 4 % lidocaine for 15 min in most cases of Grade I or II. The patients of Grade III and a part of Grade I and II were anesthetized by injecting 1.0 % lidocaine with epinephrine.

Both of the procedures described above were performed under the microscope by oto-microsurgery. A gelatin sponge slightly larger than the defect was immersed in b-FGF (NPC-18; Trafermin, a recombinant human b-FGF); the sponge was placed such that it was in contact with the edge of the defect. Fibrin glue was dripped over the sponge to form a seal.
Four weeks after the procedure, the effectiveness of this treatment was evaluated by the images of fi berscope and microscope. In cases in which complete closure of the defect was not achieved, the above treatment was repeated up to Four times.

Outcome(s)

Primary Outcome

Efficacy; complete closure of the defect after 16 weeks the final regenerative procedure.
Safety;Adverse Event ,side effect, clinical laboratory test,vital signs

Secondary Outcome

1) Completing of soft tissue defects in the ear canal at week 4 after the regenerative procedures.
2) Number of regenerative procedures
3) Closure rate of soft tissue defects in the ear canal at 4 and 16 weeks after the final regenerative procedures.
4) Presence of self-cleaning function, at 20 and 24 weeks after the final regenerative procedures.

Key inclusion & exclusion criteria

• Age minimum: >= 12age old
• Age maximum: < 90age old
• Gender: Both

Include criteria

1)Subject has given written informed consent. For subject under 18 years of age, subject and their legal representatives (care givers, parents) have given written consent (or assent if under 16 years of age).
2)Subject aged between 12 and 90 years of age at the time of consent.
3)Subject has unilateral intractable Grade I soft tissue defect of external auditory meatus (EAM) due to trauma inflicted 3 months or more prior to study treatment initiation.
4)Subject has soft tissue defect of EAM which has not tended to heal at least 3 weeks or more from screening phase (Visit S1) to the start day of study treatment initiation (Visit T1), if unilateral Grade I soft tissue defect of EAM due to trauma occurred less than 3 months prior to study treatment initiation.
5)Subject has unilateral Grade II or III soft tissue defect of EAM due to trauma inflicted one month or more prior to study treatment initiation.
6)Subject has or is expected to have unilateral soft tissue defect of EAM due to surgical treatment.

Exclude criteria

1)Subject has soft tissue defect of EAM due to burns or radiotherapy.*
2)Subject has external auditory canal cholesteatoma extending within the mastoid cells or within the tympanic cavity.*
3)Subject has malignancy/suspected malignancy or a history of malignancy in the ear.*
4)Subject has otitis externa or active otitis media.*
5)Subject has infection or otorrhea of tympanic membrane, EAM, middle ear or tympanic cavity detected by inspection through a microscope.*
6)Subject has a history of external or middle ear surgery.*
7)Subject has uncontrolled diabetes mellitus (HbA1c levels of 8.0 percent or more).
8)Subject has autoimmune diseases.
9)Subject has a history of malignancy or malignancy within 3 years prior to the time of consent.
10)Subject has received any immunosuppressants.
11)Subject has received any form of corticosteroids such as oral medications, ear drops or injections.
12)Subject has received any form of anticoagulants (warfarin, direct-acting oral anticoagulants, heparin, etc.), thrombolytics or antiplatelet agents (aspirin, clopidogrel, etc.) and cannot be withdrawn for medical reasons before or after ear canal revision.
13)Subject has received any coagulant (snake venom preparation) or antifibrinolytic.
14)Prothrombin time-international standard ratio (PT-INR)>1.5xULM.
15)Activated partial thromboplastin time (APTT) >1.5xULM.
16)Subject has a history of hypersensitivity to any of lidocaine or fibroblast growth factor (b-FGF).
17)Subject has a history of hypersensitivity to any of gelatin sponge or gelatin.
18)Subject has a history of hypersensitivity to antibiotics.
19)Female subject is pregnant or breastfeeding, or male subject is expecting to conceive or father children during the study period/Subject is unable to use any adequate contraception such as condoms, pills, pessaries, IUDs, implantable devices, spermicides, etc. during the study period.
20)Subject has a known history of a positive test for hepatitis B virus (HBsAg), hepatitis C virus (HCVAb), human immunodeficiency virus (HIVAg or Ab) or syphilis serology.
21)Subject has a history of alcohol or drug abuse.
22)Subject has any significant disease including hepatic, renal, cardiovascular, respiratory, hematological or metabolic disease.
23)Subject has any neuropsychiatric disease.
24)Subject has participated in any other clinical trial or has received any other study drug within 3 months prior to consent.
25)Subject has bilateral soft tissue defects of EAM due to trauma occurred.
26)Otherwise, subject is determined to be ineligible for this study by the investigator or sub-investigator.

*The ear conducting the protocol treatment

Related Information

• Primary Sponsor: Kanemaru Shin-ichi
• Secondary Sponsor: Fujita Yasuyuki
• Source(s) of Monetary Support: Nobelpharma Co., Ltd.