Clinical Trials Register

Summary
EudraCT Number:	2018-000812-47
Sponsor's Protocol Code Number:	SENS401-201
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2018-09-04
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2018-000812-47

A.3

Full title of the trial

A two- part, randomized, double-blind, placebo-controlled, parallel-group, efficacy and safety study of SENS-401 in subjects with severe or profound sudden sensorineural hearing loss

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A study to evaluate the use of SENS-401 in subjects with sudden deafness

A.3.2

Name or abbreviated title of the trial where available

AUDIBLE-S

A.4.1

Sponsor's protocol code number

SENS401-201

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	SENSORION SA
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	SENSORION SA
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	SENSORION SA
B.5.2	Functional name of contact point	Judith Laredo
B.5.3	Address:
B.5.3.1	Street Address	375 rue du Professeur Joseph Blayac
B.5.3.2	Town/ city	Montpellier
B.5.3.3	Post code	34080
B.5.3.4	Country	France
B.5.4	Telephone number	+33 4 34 08 71 16
B.5.6	E-mail	Judith.laredo@sensorion-pharma.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EMA/OD/114/16
D.3 Description of the IMP
D.3.1	Product name	SENS-401 ((R)-azasetron besylate)
D.3.2	Product code	SENS-401
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	-
D.3.9.1	CAS number	2025360-91-0
D.3.9.2	Current sponsor code	SENS-401
D.3.9.3	Other descriptive name	CML1882, (R)-Azasetron besylate
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Sudden sensorineural hearing loss (SSNHL)

E.1.1.1

Medical condition in easily understood language

Sudden deafness

E.1.1.2

Therapeutic area

Diseases [C] - Ear, nose and throat diseases [C09]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10040016
E.1.2	Term	Sensorineural hearing loss
E.1.2	System Organ Class	100000004854

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the efficacy of SENS-401 on hearing loss in comparison to placebo at the end of the 4-week treatment period.

E.2.2

Secondary objectives of the trial

To confirm the maintenance of any early efficacy on hearing loss at 12-week
To evaluate the efficacy on tinnitus
To determine the dose effect on hearing loss
To confirm the safety of SENS-401 in the studied population/dosage regimen

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1 Male or female
2 Aged at least 18 years old
3 Patients with unilateral idiopathic sudden sensorineural hearing loss or unilateral/bilateral acute acoustic trauma leading to sudden sensorineural hearing loss defined by both
• 3.1. At least 1 hearing threshold of 50 dB or more amongst the 3 most affected contiguous frequencies on pure tone audiometric air conduction
testing performed 24 hours or less prior to first study treatment,
and
3.2 Mean hearing loss of 30 dB or more, averaged across the 3 most affected contiguous frequencies on pure tone audiometric air conduction
testing (PTA: Pure Tone Average) performed 24 hours or less prior to first study treatment, compared with the unaffected contralateral ear or
reference values from a pre-existing audiogram (dated less than 2 years)
4 Patients with sudden hearing loss with onset within 96 hours prior to first study drug intake.
5 Females must meet one of the following: postmenopausal defined as 12 consecutive months with no menses without an alternative medical
cause, surgically sterile, abstinent; or practicing highly effective birth control (must agree to use 2 forms of contraception [1 of which must be a barrier method]) (Appendix 4) and willing to continue to use highly effective contraception for the duration of study participation and for 30 days after the final dose of study drug). Women of childbearing potential must have a negative pregnancy test at screening before the first dose of study drug is taken. Women of childbearing potential are defined as any female who has experienced menarche and who is not permanently sterile or postmenopausal.
6 Male subjects and their female partner(s) must agree to use highly effective contraception (must agree to use 2 forms of contraception [1 of which must be a barrier method]) (Appendix 4) for the duration of study participation and for 90 days after the final dose of study drug.
7 Signed and dated written informed consent.

E.4

Principal exclusion criteria

1.Bilateral idiopathic hearing loss
2.Fluctuating hearing loss
3.History of asymetric hearing (>20dB difference between ears) to the best knowledge of the patient
4.Severe hearing loss (>90 dB) associated with unilateral (ipsilateral) complete vestibular loss
5.History of Ménière’s disease, autoimmune hearing loss, radiation-induced hearing loss, acoustic neuroma (schwannoma)
6.Previous SSNHL in the affected ear within the past 6 weeks
7.History of otosclerosis, suspected perilymph fistula or membrane rupture, suspected retro-cochlear lesion, barotrauma
8.Congenital or hereditary hearing loss
9. History of severe head or neck trauma
10. Complete loss of peripheral vestibular function on the affected side
11. Any drug-based therapy for inner ear hearing loss that is ongoing or
was performed in the past 6 weeks, except oral corticosteroids
12. Any ongoing or planned concomitant medication for the treatment
of tinnitus until 6 weeks after administration
13. Any therapy known as ototoxic (e.g. aminoglycosides, cisplatin,
loop diuretics, quinine etc.) at the current time or in the past 6 months
prior to study inclusion
14. Air-bone gap of greater than 20 dB in 3 contiguous frequencies
15. Acute chronic otitis media or otitis externa terminated less than 7
days prior to randomisation.
16. History of chronic inflammatory or suppurative ear disease or
cholesteatoma,
17. Prior ear surgery of any kind (except ventilating tubes), or cochlear
implants
18. Patients with moderate to severe renal impairment defined by a
creatinine clearance ≤ 60 ml/min (calculated using the Cockroft-Gault
formula)
19. Treatment with triptans within the 24 hours before inclusion.
20. History of drug abuse or alcoholism within the last 2 years
21. Known or suspected ongoing active infection of HIV, Hepatitis B or
C, or herpes zoster
22. Known history of, or concomitant severe hepatic, gastrointestinal,
cardiovascular, respiratory, neurological (except vertigo or tinnitus),
hematological, renal, dermatological or psychiatric disease or substance
abuse or any condition that, in the opinion of the Investigator might
interfere with the evaluation of study treatment or warrant exclusion (see list of discontinuation criteria, section 11.3.2)
23. Patients who, in the opinion of the Investigator, have any clinically
relevant findings that warrant exclusion. Examples of clinically relevant
problems include, but are not limited to, serious non-malignancyassociated
medical conditions that may be expected to limit life
expectancy or significantly increase the risk of SAEs and any condition,
psychiatric, substance abuse, or otherwise, that, in the opinion of the
Investigator, would preclude informed consent, consistent follow-up, or
compliance with any aspect of the study
24. Neurological disorders including stroke, demyelinating disease,
brain stem or cerebellar dysfunction within the last 3 months. (In case
of possible stroke of the brainstem or cerebellum, or demyelinating
disease the diagnosis should have been excluded by a MRI performed in
the past 48 hours)
25. Known hypersensitivity, allergy or intolerance to the study
medication or any history of severe abnormal drug reaction
26. Pregnant or breast-feeding
27. Mentally unable to understand the nature, objectives and possible
consequences of the trial, or refusing its constraints
28. Treatment with any investigational agent within 4 weeks prior to
randomisation or 5 half-lives of the investigational drug (whichever is
longer)
29. Prior participation in a clinical trial with SENS-401 or any past
treatment with azasetron
30. Patient is the Investigator or any Sub-Investigator, research
assistant, pharmacist, study coordinator, other staff or relative thereof
directly involved in the conduct of the protocol
31. Patients with either a history of significant arrhythmia, or a history
of conditions known to increase the proarrhythmic risk (e.g., congestive
heart failure, long QT Syndrome, hypokalemia etc...).

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is the change in pure tone audiometry (PTA); average of the hearing threshold of 3 contiguous most affected hearing frequencies in decibels as identified at study entry) in the affected ear from baseline to the end of treatment visit (Visit D28± 3).

E.5.1.1

Timepoint(s) of evaluation of this end point

baseline, Visit D28± 3

E.5.2

Secondary end point(s)

• Change in pure tone audiometry (average of the hearing threshold of
the 2 most affected hearing frequencies identified at study entry) in
affected ear from baseline to the end of treatment visit (Visit D28± 3).
• Change in pure tone audiometry (the most affected hearing
frequencies identified at study entry) in affected ear from baseline to the
end of treatment visit (Visit D28± 3).
•Change in speech discrimination threshold from baseline to Days 28,
and 84
•Frequency and severity of tinnitus at Days 7, 14, 28 and 84

E.5.2.1

Timepoint(s) of evaluation of this end point

• baseline to Days 28, and 84
• Days 7, 14, 28, and 84

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Bulgaria

Canada

Czech Republic

France

Germany

Israel

Poland

Serbia

Slovakia

Turkey

United Kingdom

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

Data Base Lock

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

275

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

183

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

Yes

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

276

F.4.2.2

In the whole clinical trial

458

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Patient will return to standard of care

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2018-09-05

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-11-14

P. End of Trial
P.	End of Trial Status	GB - no longer in EU/EEA

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