Efficacy, safety, and tolerability of Ancrod in patients with sudden hearing loss
- Conditions
- sudden sensorineural hearing loss (SSHL)MedDRA version: 20.0Level: LLTClassification code 10040016Term: Sensorineural hearing lossSystem Organ Class: 100000013775Therapeutic area: Diseases [C] - Ear, nose and throat diseases [C09]
- Registration Number
- EUCTR2012-000066-37-CZ
- Lead Sponsor
- ordmark Arzneimittel GmbH & Co. KG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 115
Patients must meet all of the following inclusion criteria in order to be eligible for this study:
1. Unilateral idiopathic sudden sensorineural hearing loss =30 dB in at least 2 consecutive frequencies in the affected ear or =20 dB in 3 consecutive frequencies based upon evaluation of 8 frequencies, 0.125, 0.25, 0.5, 1, 2, 4, 6, and 8 kHz, compared to the contralateral ear.
2. Symmetric hearing prior to onset of SSHL, according to patient’s recollection.
3. Patients with hearing loss not greater than 90dB at 0.125, 0.25, 0.5, 1, 2, 4, 6, and 8 kHz.
4. Enrollment has to be accomplished within 7 days after SSHL onset.
5. Male or female aged =18 to =70 years.
6. Women of childbearing potential who are sexually active with opposite partners have to perform adequate contraception with a combination of a highly effective method of birth control and additional barrier contraception. [Highly effective method of birth control is defined as those, alone or in combination, that result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly for the entire study duration: combined (oestrogen and gestagen) oral contraceptives, hormone implants, hormone injectables, or hormone containing intrauterine device that needed to be in place for a period of at least 2 months prior to screening. Additional barrier contraception (at least the following methods are allowed: condom of the male, diaphragm with spermicide, portio cap with spermicide) has to be used for the duration of the trial, defined as from the time of screening to at least 10 days after Day 6 (Visit 4) of the double-blind treatment phase. A single barrier method is not acceptable. Women of non-childbearing potential can be included if surgically sterile (documented complete hysterectomy or bi-tubal ligations) or post-menopausal >1 year.]
7. Men of reproductive potential must use condoms. In addition, the female partner should also be on a safe hormonal contraception (e.g. combined oral contraceptives, hormone implants, hormone injectables or hormone containing intrauterine device) or use a barrier contraception (e.g. intrauterine device, diaphragm or portio cap with spermicide), if she is of childbearing potential.
8. Ability to understand and to follow the study protocol.
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 25
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5
The presence of any of the following will exclude a patient from study enrolment:
1. Pregnant or breast-feeding female.
2. positive pregnancy test before receiving study drug
3. Body weight >140 kg.
4. Bilateral SSHL.
5. Incomplete recovery after previous SSHL.
6. Due to history of physical efforts suspected perilymph fistula or membrane rupture.
7. Previously existing, known retrocochlear hearing loss.
8. Any history of any ear operation or local inflammatory disease in the past one year
9. History of blunt or penetrating ear trauma, head trauma, barotrauma, or acoustic trauma immediately preceding SSHL.
10. History of Menière’s disease, autoimmune hearing loss, radiation-induced hearing loss, endolymphatic hydrops.
11. Treatment with steroids for any reason within the preceding 30 days.
12. History of chronic inflammatory diseases or autoimmune diseases e.g. rheumatic disease, including rheumatoid arthritis, scleroderma, lupus erythematosus, polymyalgia rheumatica, polyarteritis nodosa, temporal/giant cell arteritis, Sjögren’s syndrome, or ulcerative colitis and Crohn’s disease.
13. History of unstable angina, coronary artery stenting or bypass grafting within three months of enrolment, transient ischemic attacks or stroke within four weeks of enrolment.
14. Prior chemotherapy or treatment with immunosuppressant drugs (azathioprine, chlorambucil, cyclophosphamide, or other alkylating agents), cyclosporine, etanercept, infliximab, interferon or any therapy with drugs known as ototoxic (e.g. aminoglycosides, cisplatin, loop diuretics, quinine etc.) in the past 6 months.
15. Gastrointestinal pathology: lesions liable to bleed such as active peptic ulcer disease, inflammatory bowel disease, history of gastrointestinal bleeding, or recent hemorrhage at any anatomical site requiring medical intervention.
16. Screening plasma fibrinogen level of <180 mg/dL.
17. Known disorder of platelet function or coagulation abnormality.
18. Platelet count of <100,000/mm3.
19. Severe liver disease.
20. Hepatic failure (e.g., aspartate aminotransferase (SGOT) or alanine aminotransferase (SGPT) =3 × upper limit of normal [ULN])
21. Treatment with hyperbaric oxygen within one week prior to study drug.
22. Renal insufficiency (e.g., blood urea nitrogen or creatinine =2 × ULN) or patients on renal dialysis.
23. Use of another investigational drug within 30 days prior to SSHL onset.
24. Any other serious medical condition that might interfere with subject evaluation over the 90-day study period, based on the investigator’s judgment, e.g. planned surgical intervention or any other condition which might give doubt for non-completing the study e.g. planned holiday, distance between investigational center and place of origin.
25. Known hypersensitivity to the drug substance or excipients.
26. Blood or blood product infusion within one week prior to study drug.
27. Use of any prohibited drug listed in chapter 6.4.1 and 6.4.2 of this study protocol.
28. Immunoglobulin infusion 4 weeks prior to study drug.
29. Planned treatment using intramuscular injections (e.g. vaccinations, vitamin B therapy)
30. Conditions associated with an increased risk of hemorrhaging such as major surgery, history of hemorrhagic stroke, intracranial hematoma, subarachnoid hemorrhage, diabetic retinopathy, retinopathy grade 3 or worse, known hemostatic disorders.
31. Uremia and renal colic with calculus, cerebrovascular accident, and history of neurosurgery
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Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The aim of this study is to evaluate the efficacy of ancrod treatment on hearing ability in patients suffering from SSHL.<br>The primary objective of this study is to determine the efficacy of ancrod as primary treatment of SSHL compared to placebo in patients with unilateral sudden sensorineural hearing loss as determined by audiometry.;Secondary Objective: The secondary objectives of this study are to evaluate:<br>- The relationship between biomarkers and clinical efficacy.<br>- The safety and tolerability of ancrod.<br>;Primary end point(s): The primary outcome measure for this study is the change in pure tone audiogram (PTA) in the affected ear from screening until Day 8. The PTA will be calculated as the arithmetic mean of air conduction thresholds at the affected consecutive frequencies in the frequency range of 0.125 to 8 kHz. A non-affected frequency within two affected frequencies will be included.;Timepoint(s) of evaluation of this end point: Day 8
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Secondary outcome measures will include:<br>- Change in word recognition score from screening to Day 8, Day 30 and Day 90.<br>- Change of audiogram in the affected ear from screening to Day 30 and Day 90.<br>- Change in fibrinogen concentration from screening to Day 2 and Day 8.<br>- Change in biomarkers from screening to Day 8.<br>- Patient assessment of change in hearing impairment.<br>- Physician assessment of change in hearing impairment.<br>- Change in tinnitus severity.;Timepoint(s) of evaluation of this end point: Day 2, 8, 30, 90