Efficacy of Injectable Gentamicin in Hereditary Ichthyosis (GENTIC)

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Ichthyosis
• Intervention / Treatment: Drug: Gentamicin Injectable Solution

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.

• Study Type: Interventional
• Enrollment (Estimated): 26
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: SEVERINO-FREIRE Maella, MD; Phone Number: 33 05 67 77 81 41; Email: severino-freire.m@chu-toulouse.fr
• Study Contact Backup: Name: TEXIER Hélène; Phone Number: 33 05 67 77 81 80; Email: texier.h@chu-toulouse.fr

Study Locations

• France
  • Paris, France, 75010
    • Hôpital Saint-Louis APHP
    • Contact: BOURRAT Emmanuelle, MD; Phone Number: 33 01 42 49 90 90; Email: emmanuelle.bourrat@aphp.fr
  • Toulouse, France, 31059
    • CHU de Toulouse
    • Contact: SEVERINO-FREIRE Maella, MD; Phone Number: 33 05 67 77 81 41; Email: severino-freire.m@chu-toulouse.fr
    • Contact: TEXIER Hélène; Phone Number: 33 05 67 77 81 80; Email: texier.h@chu-toulouse.fr
    • Sub-Investigator: MAZEREEUW-HAUTIER Juliette, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gentamicin; Gentamicin injection	Drug: Gentamicin Injectable Solution; Gentamicin (10 mg/kg) will be administrated once weekly for 3 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gentamicin efficacity	Proportion of patients with a reduction in Visual Index of Ichthyosis Severity score of at least 15%	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Investigators: Principal Investigator: SEVERINO-FREIRE Maella, MD, University Hospital, Toulouse

Study record dates

Study Major Dates

• Study Start (Estimated): April 23, 2024
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: April 2, 2024
• First Submitted That Met QC Criteria: April 8, 2024
• First Posted (Actual): April 12, 2024

Study Record Updates

• Last Update Posted (Actual): April 12, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Congenital ichthyoses; injectable gentamicin
• Additional Relevant MeSH Terms: Skin Diseases; Congenital Abnormalities; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Skin Diseases, Genetic; Skin Abnormalities; Keratosis; Ichthyosiform Erythroderma, Congenital; Ichthyosis; Ichthyosis, Lamellar; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Gentamicins
• Other Study ID Numbers: RC31/22/0320

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No