GENTAMICIN SULFATE for Congenital ichthyosis | Hereditary ichthyosis

Inclusion criteria

• {"criterion_text":"- Adult patients (≥18 years) affiliated to a social insurance protection regimen\n- 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)\n- 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)\n- 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

• {"criterion_text":"- Cutaneous signs suggesting a surinfection\n- Patient under guardianship, curatorship or deprived of their liberty\n- Variation greater than 15% in the VIIS score between two baseline measurements at the end of the \"run-in\"period\n- Hypersensibility of active substance or one of the gentamicin excipients\n- Administration of an aminoside in the previous 3 months\n- Treatment with nephrotoxic or ototoxic medication in the previous 6 weeks\n- 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\n- Subjects >75 years (physiological impairment of kidney function)\n- Left ventricular insufficiency\n- Hypoalbuminemia\n- Myasthenia\n- History of necrosis at the injection site during previous treatment with aminosid\n- Patient with pre-existing neuromuscular disease\n- Patient participating in another clinical study with an investigational treatment\n- Grade B or C cirrhosis according to Child-Pugh classification\n- Nephropathy or other situation at risk of renal dysfunction\n- Renal insufficiency with GFR < 60mL/min\n- 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\n- Patient who modify his keratolytic or emollient treatment in the last two weeks previous the inclusion visit\n- Patient who modify his retinoid topic treatment in the month previous the inclusion visit\n- Patient who modify his systemic retinoid treatment in the 3 months previous the inclusion visit"}

Primary endpoints

• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Decrease in VIIS score of at least 15% at month 3 versus baseline, where VIIS (Visual Index of Ichthyosis Severity) calculates severity based on assessment of scales and erythema in 4 different areas; baseline defined as mean of M-3, M-2, M-1, M0."}

Secondary endpoints

• {"endpoint_text":"- Evaluation of the severity of scaling and erythema by the VIIS score, at M1, M2, M4, M5, M6 and M9 versus baseline","definition_or_measurement_approach":"Severity assessed using VIIS score at specified months versus baseline."}
• {"endpoint_text":"- Evaluation of pruritus by VAS 0-10 at M1, M2, M3, M4, M5, M6 and M9, versus baseline","definition_or_measurement_approach":"Pruritus measured by Visual Analogue Scale (VAS) 0-10 at specified months versus baseline."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"TEWL measured on anterior forearm using a tewameter at specified months versus baseline."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Safety monitored via adverse event collection plus laboratory and functional tests: creatinine/creatinine clearance (before each injection), bacteriology with antibiogram (baseline, M3, M6), vestibular tests including VNS, audiogram, video Head Impulse Test and videonystagmography at specified timepoints."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Investigator and patient global assessments performed at specified months versus baseline."}
• {"endpoint_text":"- Evaluation of protein expression on skin biopsy from the inner arm, by western blot (quantitative analysis), at M3 versus baseline","definition_or_measurement_approach":"Quantitative western blot analysis of target protein expression on skin biopsy from inner arm at M3 versus baseline."}
• {"endpoint_text":"- Evaluation of quality of life by the IQoL-32 score (specific to ichthyosis) at M3, M6 and M9, versus baseline,","definition_or_measurement_approach":"Quality of life assessed using IQoL-32 questionnaire at specified months versus baseline."}
• {"endpoint_text":"- Global satisfaction questionnaire completed by the patient at M6","definition_or_measurement_approach":"Patient-completed global satisfaction questionnaire at month 6."}

France

Earliest CTIS Part Ii Submission Date

30-01-2024

Latest Decision Or Authorization Date

30-03-2026

Processing Time Days

790

Number Of Sites

3

Number Of Participants

26

Primary sponsor

Full Name

Centre Hospitalier Universitaire De Toulouse

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"DGOS","duties_or_roles":"Source of monetary support","organisation_type":""}
• {"country":"Ireland","full_name":"PANPHARMA","duties_or_roles":"Marketing authorisation holder / product manufacturer (listed in product information)","organisation_type":""}