E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute Unilateral Vestibulopathy |
|
E.1.1.1 | Medical condition in easily understood language |
Severe acute vertigo due to inner ear disease |
|
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 | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10047393 |
E.1.2 | Term | Vestibular neuronitis |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
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-111 in Acute Unilateral Vestibulopathy (AUV) |
|
E.2.2 | Secondary objectives of the trial |
-to explore the effect of SENS-111 on quality of life
- to determine the optimal dose regimen for SENS-111
- to evaluate safety and tolerability of SENS-111 in patients with AUV
- to evaluate the effect of SENS-111 on long term recovery of vestibular function
-to characterize the plasma exposure to SENS-111 in patients with AUV
-to preliminary evaluate the health economics of SENS-111 |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female patients
2. Aged ≥18 years and <75 years
3. Suffering from an acute episode of vertigo of peripheral origin defined as:
a.Severe (≥ 60mm on the standing vertigo intensity visual analog scale)
b.Prolonged (more than 6 hours),
c.Associated with imbalance (and/or postural imbalance) and nausea (and/or vomiting)
d.Spontaneous nystagmus toward the unaffected ear (fast phase) which is suppressed or reduced by visual fixation confirmed by oculography
e.Gain of the vestibulo ocular reflex (VOR) <0.7, measured by the video- head impulse test (HIT) and/or difference between the 2 labyrinths >25% according to the caloric test (de Jongkees’ formula).
4. Affiliated or is a beneficiary to a health insurance system (if applicable in the national regulations)
5. Signed and dated written informed consent. |
|
E.4 | Principal exclusion criteria |
1. Vertigo duration of less than 6 hours before randomization
2. Acute continuous vertigo lasting more than 72 hours prior to randomization
3. Acute hearing loss during or after the onset of vertigo.
4. Acute unilateral tinnitus during or after the onset of vertigo
5. History of acute or chronic vestibular diseases (including Ménière’s disease, acute labyrinthitis, vestibular migraine...), vestibular dysfunction, previous episode of acute unilateral vestibulopathy or prolonged vertigo.
6. Ongoing Benign paroxysmal positional vertigo (BPPV)
7. History of prior acute central vestibular lesion.
8. Acute or chronic disease of middle ear (infections, otitis)
9. Concurrent Varicella Zoster Virus (VZV) ear infection (Herpes zoster oticus)
10. History of cochlear implants
11. Neurological disorders including stroke, brainstem or cerebellar dysfunction within the last 3 months (In case of possible stroke of the brainstem or cerebellum, the diagnosis should have been excluded by a MRI performed in the past 48 hours)
12. Past or concomitant treatment with ototoxic chemotherapy
13. Past history of seizures or convulsions
14. Head trauma within the last 10 days prior to randomization
15. Aminoglycosides in the past 6 months given via systemic or transtympanic administration
16. Concomitant treatment with any of the followings within the last 24 hours prior to randomization if more than 3 doses have been taken:
a. Antihistamines: diphenhydramine, cyclizine, dimenhydrinate, meclizine, hydroxyzine, promethazine,
b. Cinnarizine, flunarizine
c. Central anti-dopaminergics: neuroleptics, unless the dose is stable for at least 1 month prior to randomization and no changes are expected during the course of the study
d. Benzodiazepines
e. Histaminergics (e.g., betahistine)
f. Scopolamine, homatropine
g. Gabapentin, pregabalin
h. Acetylleucine, 5HT3 antagonists (ondensetron, granisetron, palonosetron etc..)
i. Piracetam, piribedil, trimetazidine,
j. Corticosteroids (oral or injectable) unless the dose is stable for at least 1 month prior to randomization and no changes are expected during the course of the study
17. Treatment with any investigational agent within 4 weeks prior to randomization or 5 half-lives of the investigational drug (whichever is longer)
18. Prior participation in a clinical trial with SENS-111
19. History of malignancy other than effectively treated carcinoma in-situ of the cervix, or adequately treated non-metastatic squamous or basal cell carcinoma of the skin, within 5 years
20. Known history of, or concomitant severe hepatic, gastrointestinal, cardiovascular, respiratory, neurological, psychiatric, hematological, renal, or dermatological disease, or any condition, psychiatric, substance abuse, or otherwise, that, in the opinion of the Investigator might interfere with the evaluation of study treatment or warrant exclusion.
21. Pregnancy (a negative pregnancy test is required for all women of childbearing potential (WOCBP) before initiation of treatment
22. Male and female patients of child-bearing potential who are unwilling to use an highly effective
contraception while enrolled on study and receiving the experimental drug, and for at least 1
month after the last intake of the investigational product. Highly effective therapy includes
a. Combined (estrogen and progestogen containing) hormonal contraception associated
with inhibition of ovulation: oral, intravaginal or transdermal
b. Progestogen-only hormonal contraception associated with inhibition of ovulation: oral,
injectable or implantable
c. Intrauterine device (IUD),
d. Intrauterine hormone-releasing system (IUS)
e. Bilateral tubal occlusion
f. Vasectomised partner
g. Sexual abstinence
(see complete list in Appendix 11)
23. Nursing mothers
24. Severe abnormal laboratory findings
a. Creatininemia >1.5 upper limit of normal (ULN))
b. INR >1.7 ULN, Total bilirubin >2 ULN
c. ALAT and/or ASAT > 3 x ULN
d. Hemoglobin <0.9 Giga/L and/or
e. Neutrophils <1,5 Giga/L and/or
f. Platelets <100 Giga/L
25. Patients who, in the opinion of the Investigator, have significant medical or psychosocial findings that warrant exclusion. Examples of significant problems include, but are not limited to other serious non-malignancy-associated medical conditions that may be expected to limit life expectancy or significantly increase the risk of serious adverse event (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
26. 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 |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the vertigo intensity measured by the AUC of the Vertigo Intensity Visual Analogue Scale (VI-VAS) in standing position over the 4 treatment days (8 post baseline assessments) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Over the 4 treatment days |
|
E.5.2 | Secondary end point(s) |
- worst spontaneous vertigo intensity measured by the AUC of the worst vertigo visual analogue scale (VI-VAS) over the 4 treatment days (8 hours post baseline assessment)
- Change from baseline of the total score of the Romberg tests at the end of the treatment (D5) and end of study (D28)
- Peak slow phase velocity of the peripheral vestibular spontaneous nystagmus, measured by oculography in darkness at the end of treatment (D5) and the end of study (D28)
-Nausea intensity measured by the AUC of the Nausea Intensity Visual Analogue Scale over the 4 treatment days (8post baseline assessments)
- The functional disability at the end of study (D28) assessed by the Dizziness Handicap Inventory (DHI) functional subscale score and the Vestibular Disorder Activities of Daily Living Scale (VADL) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
- worst spontaneous vertigo intensity: over the 4 treatment days (8 hours post baseline assessment)
- Change from baseline of the total score of the Romberg tests at the end of the treatment (D5) and end of study (D28)
- Peak slow phase velocity of the peripheral vestibular spontaneous nystagmus: at the end of treatment (D5) and the end of study (D28)
-Nausea intensity: over the 4 treatment days (8 post baseline assessments)
- The functional disability at the end of study (D28) assessed by the Dizziness Handicap Inventory (DHI) functional subscale score and the Vestibular Disorder Activities of Daily Living Scale (VADL)
|
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
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 | No |
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 |
Korea, Democratic People's Republic of |
United States |
|
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
|
|
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 | 20 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 20 |