First-in-human, placebo-controlled, ascending dose study to assess the safety, tolerability and pharmacokinetics of a single intratympanic injection of AC102 in healthy volunteers

Completed

• Conditions: hearing impairment; now healty volunteers); tinnitus (at a later stage; 10019243

• Registration Number: NL-OMON55334
• Lead Sponsor: AudioCure Pharma GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 42

Inclusion Criteria

1. Signed Institutional Review Board (IRB) / Independent Ethics Committee (IEC)
approved informed consent form (ICF)
2. Willing and able to attend the trial visits
3. Able to read and understand trial documents and follow Investigator and
trial personnel instructions during visits, including audiology measurements
4. Female or male
5. Age * 18 years and * 40 years at the day of Screening
6. Body mass index (BMI) 18.0 - 30.0 kg/m2, inclusive, where BMI (kg/m2) <= body
weight (kg) / height2*(m2) at Screening Visit
7. Healthy as judged by a responsible physician with no clinically significant
abnormality identified on the medical or laboratory evaluation, including
12-lead ECG, vital sign assessment or physical examination
8. Normal age-related hearing in both ears according to DIN EN ISO 8253-1 and
DIN 7029:2017
9. Willing and able to use adequate hearing protection and to refrain from
engaging in activities or work involving loud noise exposure where sufficient
hearing protection is not possible or ensured for the duration of their
participation in this study
10. Willing and able to protect the ear canal and middle ear from water
exposure for as long as the tympanic membrane is not fully closed
11. A female volunteer must meet one of the following criteria:
* If of childbearing potential * agrees to use one of the accepted
contraceptive regimens from at least 28 days prior to until at least 30 days
after study medication administration. An acceptable method of contraception
includes at least one of the following:
a. Abstinence from heterosexual intercourse
b. Combined (contains estrogen and progestogen) hormonal contraception (oral,
vaginal, transdermal)
c. Progestogen only contraception (oral, injectable, implantable)
d. Intrauterine device
e. Intrauterine hormone-releasing system
f. Bilateral tubal ligation
g. Vasectomized partner
* If of non-childbearing potential * should be surgically sterile (i.e. has
undergone complete hysterectomy, bilateral oophorectomy, or bilateral tubal
ligation) or in a postmenopausal state (at least one year without menses at
Screening)
12. A male volunteer with sexual partners who are pregnant, possibly pregnant,
or who could become pregnant must meet the following criteria:
* Subject is unable to procreate, defined as surgically sterile (i.e. has
undergone a vasectomy at last 6 months before Screening)
* Subject agrees to use one of the accepted contraceptive regimens until 90
days after study medication administration. An acceptable method of
contraception includes one of the following:
a. Abstinence from heterosexual intercourse
b. Condom with spermicide.

Exclusion Criteria

1. History of acute hearing loss from noise trauma, barotrauma or head trauma
in either ear at any time
2. History of idiopathic sudden sensorineural hearing loss in the past 2 years
3. Congenital hearing loss
4. History of chronic (> 6 months) noise exposure (for leisure or profession)
5. Chronic or acute tinnitus in either ear
6. Current vertigo/previous balance or vestibular disorders
7. Any clinically significant external or middle-ear pathology observed by
otoscopic examination or tympanometry (i.e. reduced mobility of the tympanic
membrane)
8. Any clinically significant abnormality of the tympanic membrane or the outer
ear canal in the selected ear that would preclude intratympanic administration
9. Absence of detectable OAEs in the frequency band with a concomitant
clinically significant increase in hearing thresholds in accordance with DIN EN
ISO 8253-1 and DIN 7029:2017
10. Known family history of hearing impairment, other than age related
11. History of autoimmune hearing loss, radiation-induced hearing loss,
fluctuating hearing, endolymphatic hydrops or Menière*s disease in either ear
12. History of chronic inflammatory or suppurative ear disease or cholesteatoma
13. Current evidence or history of acoustic neuroma or other retrocochlear
damage
14. History of otosclerosis
15. Suspected perilymph fistula or membrane rupture in either ear
16. Otitis media or otitis externa that is ongoing or ended within 30 days
prior to study treatment or is occurring several times per year
17. Radiation therapy in the head and neck area
18. Any therapy known as ototoxic (e.g. aminoglycosides [systemic or
ototopical], cisplatin, loop diuretics, quinine etc.)
19. Taking any anti-coagulant medication (direct oral anticoagulant [DOAC],
e.g. Apixaban®), vitamin K antagonists (e.g. Marcumar®), thrombocyte
aggregation blockers (e.g. Aspirin®) chronically or Aspirin® as a pain killer
acutely within one week before treatment
20. History or presence of drug abuse or alcoholism within the past 2 years
21. Positive urine screen of drugs of abuse (if not due to concomitant
medication, e.g. benzodiazepines as hypnotics) or alcohol breath test at
Screening or Day -1
22. Ingestion of alcohol within 48 hours prior to study medication
administration and during the in-house period.
23. Current smokers
24. Excess in xanthine consumption (more than 5 cups of coffee/day or
equivalent)
25. Subjects with diagnosed anxiety disorders, psychosis, depression,
schizophrenia, attempted suicide or other significant psychiatric conditions
that can impact their ability to cooperate and comply with the study protocol
26. Any clinically relevant autoimmune, respiratory, cardiovascular, hepatic,
gastrointestinal, renal, dermatological, neurological or other abnormality that
in the opinion of the Investigator may pose a safety risk to a subject in this
study, which may confound safety assessment, or may interfere with study
participation or the evaluation of study treatment
27. Known human immunodeficiency virus (HIV), hepatitis B or hepatitis C
infection
28. Having an active infection with SARS-CoV-2
29. Abnormal and clinically relevant laboratory results
30. Systemic steroids within the last three months (topical steroids like nasal
spray or cremes are allowed)
31. Seated pulse rate

Study & Design

• Study Type: Interventional
• Study Design: Not specified