Phase 2 study evaluating the efficacy of injectable gentamicin in hereditary ichthyosis - GENTIC

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Toulouse

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

29 Jan 2025 → ongoing

Decision date (initial)

2024-02-06

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

DGOS

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To evaluate the efficacy of gentamicin on the severity of scales and erythema, at M3 versus baseline in moderate to severe congenital ichthyosis caused by a nonsense mutation

Secondary objectives 8

1. Describe the efficacy of gentamicin on the severity of scales and erythema at M1, M2, M4, M5, M6 and M9, versus baseline
2. Describe the efficacy of gentamicin on the importance of pruritus at M1, M2, M3, M4, M5, M6 and M9, versus baseline
3. Describe the efficacy of gentamicin on the importance in transepidermal water loss measurement (TEWL), at M1, M2, M3 and M6, versus baseline
4. Describe the safety of systemic gentamicin
5. Describe the efficacy of gentamicin on the overall clinical severity at M1, M2, M3, M4, M5, M6 and M9 versus baseline
6. Describe the efficacy of gentamicin on the protein expression of the target protein on skin biopsy with M3 versus baseline
7. Describe the efficacy of gentamicin on the quality of life at M3, M6 and M9 versus baseline
8. Describe the overall patient satisfaction at M6

Conditions and MedDRA coding

Congenital Ichthyosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Adult patients (≥18 years) affiliated to a social insurance protection regimen
2. Hereditiary ichthyosis caused by a homozygous non-sense mutation of a gene responsible for hereditiary ichthyosis (TGM1, PNPLA1, ALOX12B, NIPAL4, ALOXE3, SDR9C7, ABCA12, CERS3, SPINK5 and CDSN)
3. Moderate to severe forms of ichthyosis defined as VIIS score at 2-3 on at least 2 out of 4 areas evaluated (back, upper limbs, lower limbs, back of the foot)
4. Free, informed consent, written and signed by the participant and the investigator (at the latest on the day of inclusion and before any examination required by the research).

Exclusion criteria 21

1. Cutaneous signs suggesting a surinfection
2. History of necrosis at the injection site during previous treatment with aminosid
3. Grade B or C cirrhosis according to Child-Pugh classification
4. Nephropathy or other situation at risk of renal dysfunction
5. Renal insufficiency with GFR < 60mL/min
6. Surdity which is not caused by plug scales in the external ear canals or other situation at risk of surdity including the presence of the A1555G mutation in the 12S rRNA (mitochondrial DNA) gene
7. Patient who modify his keratolytic or emollient treatment in the last two weeks previous the inclusion visit
8. Patient who modify his retinoid topic treatment in the month previous the inclusion visit
9. Patient who modify his systemic retinoid treatment in the 3 months previous the inclusion visit
10. Patient under guardianship, curatorship or deprived of their liberty
11. Variation greater than 15% in the VIIS score between two baseline measurements at the end of the "run-in"period
12. Hypersensibility of active substance or one of the gentamicin excipients
13. Administration of an aminoside in the previous 3 months
14. Treatment with nephrotoxic or ototoxic medication in the previous 6 weeks
15. Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study. Women of childbearing age, potentially sexually active, and unwilling to use acceptable contraceptive measures in accordance with CTFG recommandations
16. Subjects >75 years (physiological impairment of kidney function)
17. Left ventricular insufficiency
18. Hypoalbuminemia
19. Myasthenia
20. Patient with pre-existing neuromuscular disease
21. Patient participating in another clinical study with an investigational treatment

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of patients with a decrease in VIIS (Visual Index of Ichthyosis Severity) score (which calculates severity based on assessment of scales and erythema in 4 different areas) of at least 15% at M3 versus baseline (mean M-3, M-2, M-1, M0)

Secondary endpoints 8

1. Evaluation of the severity of scaling and erythema by the VIIS score, at M1, M2, M4, M5, M6 and M9 versus baseline
2. Evaluation of pruritus by VAS 0-10 at M1, M2, M3, M4, M5, M6 and M9, versus baseline
3. Evaluation of TEWL (transepidermal water loss) measured on the anterior aspect of the forearm (area classically chosen for measurement) using a tewameter at M1, M2, M3 and M6, versus baseline
4. Collection of adverse events throughout the study: creatinine and creatinine clearance (before each injection), bacteriology with antibiogram (baseline, M3 and M6), vestibular function test (baseline, M1, M2, M3 and M6) for nystagmus by videonystagmoscopy (VNS), audiogram (baseline, M1, M2, M3 and M6) and video Head Impulse Test (baseline, M1, M2, M3 and M6) and videonystagmography (baseline and M6)
5. Evaluation of the physician's IGA (Investigator Global Assessment) and the patient's PtGA (Patient Global Assessment) (at M1, M2, M3, M4, M5, M6 and M9, versus baseline
6. Evaluation of protein expression on skin biopsy from the inner arm, by western blot (quantitative analysis), at M3 versus baseline
7. Evaluation of quality of life by the IQoL-32 score (specific to ichthyosis) at M3, M6 and M9, versus baseline,
8. Global satisfaction questionnaire completed by the patient at M6

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Toulouse

Sponsor organisation

Centre Hospitalier Universitaire De Toulouse

Address

2 Rue Viguerie

City

Toulouse

Postcode

31300

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Toulouse

Contact name

SEVERINO-FREIRE Maella

Public contact point

Organisation

Centre Hospitalier Universitaire De Toulouse

Contact name

SEVERINO-FREIRE Maella

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications