Treatment with PBI-4050 in patients with Alström syndrome: study protocol for a phase 2, single-Centre, single-arm, open-label trial

• DOI: 10.1186/s12902-018-0315-6
• Publication Date: 2018-11-26T14:07:32Z
• Authors: Shanat Baig; Vishy Veeranna; Shaun Bolton; Nicola Edwards; Jeremy W. Tomlinson; Konstantinos Mano...; John Moran; Richard P. Steeds; Tarekegn Geberhiwot
• Keywords: Liver Cirrhosis; Male; 0301 basic medicine; Anti-Inflammatory Agents; Insulin resistance; RC648-665; Fibrosis; Metabolic syndrome; Diseases of the endocrine glands. Clinical endocrinology; 3. Good health; Study Protocol; 03 medical and health sciences; Diabetes mellitus; Treatment Outcome; Alström syndrome; Humans; Female; Obesity; Alstrom Syndrome

Alström syndrome (ALMS) is a very rare autosomal recessive monogenic disorder caused by mutation in the ALMS1 gene and characterised childhood onset obesity, dyslipidaemia, advanced non-alcoholic fatty liver disease, diabetes extreme insulin resistance. There evidence of multi-organ fibrosis ALMS severity disease often leads to organ failure with associated morbidities, resulting reduced life expectancy. are no specific treatments for this current management consists only symptomatic therapies. PBI-4050 new molecular entity demonstrated anti-inflammatory anti-fibrotic activities preclinical models, including animal models human diseases characterized progressive kidney, heart, lungs. Moreover, completed Phase 2 studies type mellitus metabolic idiopathic pulmonary further support activity PBI-4050. Together, these data suggest that has potential treat pathological inflammatory fibrotic features ALMS. The aim study evaluate safety & subjects This 2, single-centre, single-arm, open-label trial. A total 18 patients will be enrolled receive at daily oral dose 800 mg an initial 24 weeks continuation additional 36 or 48 weeks. Standard assessments include adverse events, clinical laboratory tests, vital signs, physical examination electrocardiograms. Efficacy adipose tissue biopsy, hyperinsulinaemic-euglycaemic glucose clamp, microdialysis, transient elastography, cardiac magnetic resonance imaging, blood tests. first Given rarity complexity design been chosen maximise subject exposure increase likelihood achieving our endpoints. results provide valuable preliminary effects ALMS, heterogeneous premature mortality. trial registered on ClinicalTrials.gov (Identifier; NCT02739217 , February 2016) European Union Drug Regulating Authorities Clinical Trials (EudraCT Number 2015–001625-16, Sept 2015).