FERRIC DERISOMALTOSE for Restless legs syndrome

Inclusion criteria

• {"criterion_text":"- RLS diagnosed according to the current IRLSSG criteria Essential diagnostic criteria (all must be met): a) An urge to move the legs usually but not always accompanied by, or felt to be caused by, uncomfortable and unpleasant sensation in the legs. b) The urge to move the legs and any accompanying unpleasant sensations begin or worsen during periods of rest or inactivity such as lying down or sitting c) The urge to move the legs and any accompanying unpleasant sensations are partially or totally relieved by movement, such as walking or stretching, at least as long as the activity continues. d) The urge to move the legs and any accompanying unpleasant sensations during rest or inactivity only occur or are worse in the evening or night than during the day. d) The occurence of the above features is not solely accounted for as symptoms primary to another medical or a behavioral condition (e.g. myalgia, venous stasis, leg edema, arthritis, leg cramps, positional discomfort, habitual foot tapping)."}
• {"criterion_text":"- Female and male participants aged ≥ 18 years"}
• {"criterion_text":"- Negative urine/serum pregnancy test in women of childbearing potential (WOCBP). WOCBP who are sexually active, agree to use highly effective means of contraception during the study and for at least 1 month post-study treatment. Allowed are accepted and effective hormonal/non-hormonal methods of contraception and sexual abstinence or vasectomised partners (> 3 months previously). Vasectomy has to be confirmed by two negative semen analyses."}
• {"criterion_text":"- IRLS score >=15"}
• {"criterion_text":"- For the DA group, DA dosage not exceeding the max recommended dosage for RLS (PMID 27448465): Pramipexole 0.75 mg/day, Ropinirole 4mg/day, Rotigotine 3 mg/day"}
• {"criterion_text":"- Written, signed and dated informed consent"}

Exclusion criteria

• {"criterion_text":"- Secondary RLS"}
• {"criterion_text":"- Ferritin > 200 mg/dL or Transferrin Saturation over 45%"}
• {"criterion_text":"- Phosphate levels below the lower limit normal before study drug initiation"}
• {"criterion_text":"- Contraindications for performing a MRI (for example claustrophobia, pacemakers, metal implants)"}
• {"criterion_text":"- Body weight < 50 kg"}
• {"criterion_text":"- Known Hypersensitivity to the active substance or any of its excipients (Sodium hydroxide/Hydrochloric acid"}
• {"criterion_text":"- Sporadic RLS"}
• {"criterion_text":"- Dialysis-dependent renal failure (eGFR<20mL/min/1.73m² calculated by MDRD formula)"}
• {"criterion_text":"- Moderate or severe heart failure (NYHA III - IV)"}
• {"criterion_text":"- Malignancies"}
• {"criterion_text":"- Pregnancy/brestfeeding"}
• {"criterion_text":"- Known thalassaemia minima/minor, hemochromatosis, polycythemia vera, hemolytic anemia"}
• {"criterion_text":"- Current intake of opiates"}
• {"criterion_text":"- Iron substitution, erythropoietin therapy or blood transfusion in the previous 6 months"}

Primary endpoints

• {"endpoint_text":"- Changes in RLS severity as detected by the IRLS","definition_or_measurement_approach":"Measured using the International Restless Legs Severity Scale (IRLS) to assess changes in RLS severity."}

Secondary endpoints

• {"endpoint_text":"- Changes in RLS severity as detected by the sIRLS, RLS-6 and CGI","definition_or_measurement_approach":"Measured using the self-administered IRLS (sIRLS), Restless Legs Syndrome-6 (RLS-6) scale and Clinical Global Impression (CGI) scales."}
• {"endpoint_text":"- Changes in blood count, iron, Tf, TSAT, ferritin, sTfR, hepcidin-25, creatinine (GFR), GPT, GOT, LDH, CRP, electrolytes (Na, K, P, Ca), PTH, LCN2, dopamine, 1,25-(OH)2 vitamin D, 25-OH vitamin D, EPO, ERFE, PDGF-BB, LCN2 and metabolites (ATP, NADH/NAD, Lactate, Succinate, Citrate, Pyruvate, free fatty acids)","definition_or_measurement_approach":"Laboratory assays and blood tests for listed haematological, iron-related, biochemical and metabolite biomarkers."}
• {"endpoint_text":"- Changes in mitochondrial iron and Krebs cycle metabolism gene expression in monocytes detected by RT-PCR","definition_or_measurement_approach":"Gene expression measured by RT-PCR on peripheral monocytes."}
• {"endpoint_text":"- Changes in mitochondrial respiration of selected and randomly assigned patients measured with OROBOROS respirometry","definition_or_measurement_approach":"High-resolution respirometry (Oxygraph-2k / OROBOROS) to assess mitochondrial respiration in selected and randomly assigned patients (N=60)."}
• {"endpoint_text":"- Changes in iron content in the substantia nigra detected by an MRI in a subgroup of 80 patients (20 dopaminergic therapy/iron, 20 dopaminergic therapy/placebo, 20 no previous treatment/iron and 20 no previous treatment/placebo)","definition_or_measurement_approach":"MRI assessment of iron content in substantia nigra in prespecified subgroup of 80 patients with the stated stratification by prior dopaminergic therapy and treatment allocation."}

Austria

Earliest CTIS Part Ii Submission Date

16-09-2024

Latest Decision Or Authorization Date

14-10-2024

Processing Time Days

28

Number Of Sites

1

Number Of Participants

140

Primary sponsor

Full Name

Medizinische Universitaet Innsbruck

Organisation Type

Educational Institution

Country Of Registered Address

Austria