Pearson and Kearns-Sayre syndrome. MedDRA version: 20.1 Level: PT Classification code 10058799 Term: Mitochondrial encephalomyopathy System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 20.1 Level: PT Classification code 10058799 Term: Mitochondrial encephalomyopathy System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 20.1 Level: PT Classification code 10051403 Term: Mitochondrial DNA deletion System Organ Class: 10010
Conditions
Interventions
Trade Name: Lederfolin
Product Name: Lederfolin
Product Code: [Lederfolin]
Pharmaceutical Form: Granules for oral solution
INN or Proposed INN: CALCIO LEVOFOLINATO
CAS Number: 58-05-9
Current Sponsor
Sponsors
IRCCS, OSPEDALE PEDIATRICO BAMBINO GESÙ DI ROMA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Diagnosis of PS/KSS syndromes with confirmed genetic mutations associated PS/KSS syndromes. Diagnosis will be performed on review of muscle/skin biopsies, presence of mtDNa deletion on mtDNA samples from peripheral blood lymphocytes, urinary tract cells in urine, or muscle (Southern blot, Long PCR, MLPA), quantification of mtDNA deletions by Quantitative PCR. If genetic confirmation and quantification of mtDNA deletion is not available, it will performed at screening • Newcastle Pediatric Mitochondrial Disease Scale score of =15 and = 60 on sections 1-3 • Evidence of disease progression within 12 months preceeding the screening either by NPMDS score or documented evidence of neurologic deterioration • Availability of pre-enrollment brain MRI that confirms the characteristic basal ganglia damage or leukoencephalopathy of PS/KSS syndromes performed within 6 months prior to screening (if brain MRI/MRS is not available, it will performed at screening) • Male or female age 1 to 25 years • Patient or patient’s guardian able to consent and comply with protocol requirements Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 9 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Allergy to folinic acid • Clinical history of bleeding or abnormal baseline PT, PTT (or aPTT) or INR • Pernicious Anemia, • Hereditary fructose intolerance, glucose / galactose malabsorption syndrome or sucrase-isomaltase deficiency, • Not-mitochondrial Diabetes • Concomitant use of methotrexate • Clinically significant disease, such as, but not limited to, hepatitis C virus (HCV) / human Immunodeficiency virus (HIV) / hepatitis B virus (HBV) / Cancer, that precludes study participation • Diagnosis of any other concurrent inborn error of metabolism • Previous tracheostomy • Ventilator dependent or use of noninvasive ventilatory support within one month of enrollment • Hepatic insufficiency with ALT, AST, Alkaline phosphatase, Total bilirubin grater than two times upper limit of normal • Renal insufficiency requiring dialysis • End stage cardiac failure • Use of anticoagulant medications • Severe end-organ hypo-perfusion syndrome secondary to cardiac failure resulting in lactic acidosis • Pregnancy and breastfeeding women.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the clinical effects of folinic acid in patients with PS/KSS syndromes on: disease severity as assessed by the Newcastle Pediatric/Adult Mitochondrial Disease Scale (NPMDS) Sections 1-3;Secondary Objective: To evaluate the effects of folinic acid in patients with PS/KSS syndromes on: 1. Neuromuscular function as assessed by: a.6-minute walk test; b.30 sec sit to stand test; c.Caregiver burden scale d.New muscle endurance test e. Int Adult Mitoch Disease Sc f.Timed test 2. Quality of life as assessed by: a.PedsQL child-self report b.PedsQL parent-proxy report c.SF-36 for patients> 18 years d.WHO-QOL bref for parents e. Sec. 4 of NPMDS 3. Electrophysio test (VEP/ERG) 4. Disease morbidity and mortality as assessed by: a.Mortality b.Total num of medical encounters c.Total hospitalizations and hospital days d.Weight 5. Metabolomics analysis in blood and urine 6. Glutathione cycle biomarkers in blood 7. Reduced Glutathione (GSH) in the brain 8. Interferon Signature in blood and CSF immunophenotyping To examine the safety of folinic acid in children with PS/KSS syndromes by examining drug-related adverse and serious adverse events;Primary end point(s): Newcastle Pediatric Mitochondrial Disease Scale Sections 1-3;Timepoint(s) of evaluation of this end point: 24 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Weight • Neuromuscular Functional scales (6-minute walk test; 30 seconds sit to stand test; Caregiver burden scale; Grip strength; New muscle endurance test: International Paediatric/Adult Mitochondrial Disease Scale; Timed test) • Newcastle Pediatric/Adult Mitochondrial Disease Scale Section 4 • Glutathione cycle components • Metabolomics analysis in blood and urine • Brain and spinal MRI/MRS • Electrophysiological test (VEP/ERG) • Total hospitalizations and total hospital days • Total number of medical encounters • Mortality • Physical examination with vital signs • Neurological assessment • Routine assessments of AEs and SAEs • Routine serum chemistries with liver function tests, electrolytes, lactate, lipids and blood gas analysis • Routine hematology tests with coagulation tests • Adrenal gland hormone studie • 12-lead ECG, Holter ECG, Ecocardiography;Timepoint(s) of evaluation of this end point: 24 months | — |
Countries
Italy
Contacts
Public ContactU.O.C. Patologia Metabolica
Diego Martinelli
Outcome results
None listed