Efficacy of Injectable Gentamicin in Hereditary Ichthyosis

NCT ID: NCT06362447

Last Updated: 2024-09-05

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-09-30
• Study Completion Date: 2027-04-01

Brief Summary

This study will evaluate the efficacy and safety of intravenous gentamicin in congenital ichthyosis due to a non-sens mutation. The primary objective is the severity of scales and erythema at the third month, compared to baseline. Secondary objectives will include: the importance of itching, trans epidermal water loss, cutaneous expression of the targeted protein, the security of the drug and patients' satisfaction.

Detailed Description

Congenital ichthyoses represent a group of diseases characterized by disabling cutaneous anomalies (scales and inconstant erythema) often associated with extra cutaneous anomalies that may be severe. The treatment is non curative and symptomatic, including local treatments (ie. emollients). Oral retinoids may be helpful in moderate to severe forms. There is a huge need for novel therapies, ideally targeting the molecular defect. Gentamicin may be a novel therapeutic option for congenital ichthyosis.

Apart its antimicrobial effect, gentamicin can achieve stop codon readthrough and produce full-length protein.

In this study, gentamicin (10 mg/kg) will be administrated once weekly for 3 months. The study will include monthly visits, a follow-up visit 3 months after the stopping the drug and an end-of-study visit 3 months after the follow-up visit. Kidney and hearing functions will be assessed regularly.

Conditions

Ichthyosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Gentamicin

Gentamicin injection

Group Type: EXPERIMENTAL

Gentamicin Injectable Solution

Intervention Type: DRUG

Gentamicin (10 mg/kg) will be administrated once weekly for 3 months

Interventions

Gentamicin Injectable Solution

Gentamicin (10 mg/kg) will be administrated once weekly for 3 months

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Adult patients affiliated to a social insurance protection regimen.

2. Hereditary ichthyosis caused by a homozygous non-sense mutation of a gene responsible for hereditary ichthyosis (TGM1, PNPLA1, ALOX12B, NIPAL4, ALOXE3, SDR9C7, ABCA12, CERS3, SPINK5 and CDSN)

3. Moderate to severe forms of ichthyosis defined as Validating an Ichthyosis Severity Index 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

1. Cutaneous signs suggesting a surinfection

2. Hypersensibility of active substance or one of the gentamicin excipients

3. Administration of an aminoside in the previous 3 months

4. Treatment with nephrotoxic or ototoxic medication in the previous 6 weeks

5. 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 contraception measures in accordance with Clinical Trials Facilitation and Coordination Group recommendations

6. Subjects >75 years (physiological impairment of kidney function)

7. Left ventricular insufficiency

8. Hypoalbuminemia

9. Myasthenia

10. History of necrosis at the injection site during previous treatment with aminosid

11. Grade B or C cirrhosis according to Child-Pugh classification

12. Nephropathy or other situation at risk of renal dysfunction

13. Renal insufficiency with glomerular filtration rate < 60mL/min

14. 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 ribonucleic acid (mitochondrial deoxyribonucleic acid) gene

15. Patient who modify his keratolytic or emollient treatment in the last two weeks previous the inclusion visit

16. Patient who modify his retinoid topic treatment in the month previous the inclusion visit

17. Patient who modify his systemic retinoid treatment in the 3 months previous the inclusion visit

18. Patient under guardianship, curatorship or deprived of their liberty

19. Patient with pre-existing neuromuscular disease

20. Patient participating in another clinical study with investigational treatment

Variation greater than 15% in the Validating an Ichthyosis Severity Index score between two baseline measurements.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Toulouse

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

SEVERINO-FREIRE Maella, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Toulouse

Locations

Hôpital Saint-Louis APHP

Paris, France, France

CHU de Toulouse

Toulouse, France, France

Countries

France

Central Contacts

SEVERINO-FREIRE Maella, MD

Role: CONTACT

severino-freire.m@chu-toulouse.fr

05 67 77 81 41 ext. 33

TEXIER Hélène

Role: CONTACT

texier.h@chu-toulouse.fr

05 67 77 81 80 ext. 33

Facility Contacts

BOURRAT Emmanuelle, MD

Role: primary

emmanuelle.bourrat@aphp.fr

01 42 49 90 90 ext. 33

SEVERINO-FREIRE Maella, MD

Role: primary

severino-freire.m@chu-toulouse.fr

05 67 77 81 41 ext. 33

TEXIER Hélène

Role: backup

texier.h@chu-toulouse.fr

05 67 77 81 80 ext. 33

MAZEREEUW-HAUTIER Juliette, MD, PhD

Role: backup

Other Identifiers

RC31/22/0320

Identifier Type: -

Identifier Source: org_study_id