Efficacy of Injectable Gentamicin in Hereditary Ichthyosis

Ichthyosis Clinical Trial

— GENTIC  

Official title:

Phase 2 Study Evaluating the Efficacy of Injectable Gentamicin in Hereditary Ichthyosis

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06362447
• Other study ID #: RC31/22/0320
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: April 23, 2024
• Est. completion date: April 1, 2027

Study information

• Verified date: April 2024
• Source: University Hospital, Toulouse
• Contact: SEVERINO-FREIRE Maella, MD
• Phone: 05 67 77 81 41
• Email: severino-freire.m[@]chu-toulouse.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 26
• Est. completion date: April 1, 2027
• Est. primary completion date: April 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Exclusion criteria at the end of the "run-in" period:

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

Related Conditions & MeSH terms

• Ichthyosis
• Ichthyosis, Lamellar

Intervention

Drug:
• Gentamicin Injectable Solution
Gentamicin (10 mg/kg) will be administrated once weekly for 3 months

Locations

Country	Name	City	State
France	Hôpital Saint-Louis APHP	Paris
France	CHU de Toulouse	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Toulouse

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Gentamicin efficacity	Proportion of patients with a reduction in Visual Index of Ichthyosis Severity score of at least 15%	3 months
Secondary	Gentamicin efficacity	Proportion of patients with a reduction in Visual Index of Ichthyosis Severity score	Month 1, Month 2, Month 4, Month 5, Month 6 and Month 9
Secondary	Gentamicin efficacity on quality of life	Assessment of quality of life by IQoL-32 score (specific to ichthyosis)	Month 3, Month 6 and Month 9