Resumen

Estudio de fase 3, controlado con placebo, aleatorizado, de 52 semanas para evaluar la seguridad y eficacia de seladelpar en sujetos con colangitis biliar primaria (CBP) y respuesta inadecuada o intolerancia al ácido ursodesoxicólico (AUDC). Los participantes podrán ingresar al estudio de seguridad abierto en curso (NCT03301506) al finalizar este estudio doble ciego.

Descripción detallada

Primario: * Evaluar la seguridad y el efecto sobre la colestasis de dos regímenes de seladelpar (5 mg/día con titulación hasta 10 mg/día y 10 mg/día) durante 52 semanas de tratamiento en comparación con placebo. Secundario clave: * Evaluar el efecto de seladelpar sobre la normalización de los niveles de fosfatasa alcalina (FA). * Evaluar el efecto de seladelpar sobre el prurito.

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 75 YearsSexo: ALL

Criterios de inclusión

Must have given written informed consent (signed and dated) and any authorizations required by local law
to 75 years old (inclusive)
Male or female with a diagnosis of PBC, by at least two of the following criteria:
History of AP above ULN for at least six months
Positive anti-mitochondrial antibody (AMA) titers (\>1/40 on immunofluorescence or M2 positive by enzyme linked immunosorbent assay \[ELISA\]) or positive PBC-specific antinuclear antibodies
Documented liver biopsy result consistent with PBC
On a stable and recommended dose of UDCA for the past twelve months OR intolerant to UDCA (last dose of UDCA \> 3 months prior to Screening)
AP ≥ 1.67 × ULN
Females of reproductive potential must use at least one barrier contraceptive and a second effective birth control method during the study and for at least 90 days after the last dose. Male subjects who are sexually active with female partners of reproductive potential must use barrier contraception and their female partners must use a second effective birth control method during the study and for at least 90 days after the last dose

Criterios de exclusión

Previous exposure to seladelpar (MBX-8025)
A medical condition, other than PBC, that in the investigator's opinion would preclude full participation in the study or confound its results (e.g., cancer)
AST above 3 × ULN
ALT above 3 × ULN
Total bilirubin above 2.0 × ULN
Advanced PBC as defined by the Rotterdam criteria (albumin below LLN AND total bilirubin above 1 × ULN)
Creatine kinase (CK) above 1.0 × ULN
eGFR below 60 mL/min/1.73 m2 (calculated by MDRD formula)
International normalized ratio (INR) above 1.0 × ULN
Platelet count below 100 × 103/µL
Presence of clinically significant hepatic decompensation, including:
History of liver transplantation, current placement on liver transplantation list, or current MELD score ≥ 15
Complications of portal hypertension, including known esophageal varices, history of variceal bleeds or related interventions (e.g., transjugular intrahepatic portosystemic shunt placement), relevant ascites, hepatic encephalopathy
Cirrhosis with complications, including history or presence of spontaneous bacterial peritonitis
Other chronic liver diseases:
Current features of auto-immune hepatitis as determined by the investigator based on immunoserology, liver biochemistry and histology
Primary sclerosing cholangitis determined by presence of diagnostic cholangiographic findings
History or clinical evidence of alcoholic liver disease
History or clinical evidence of alpha-1-antitrypsin deficiency
Biopsy confirmed nonalcoholic steatohepatitis
History or evidence of Gilbert' Syndrome with elevated total bilirubin
History or evidence of hemochromatosis
Hepatitis B defined as presence of hepatitis B surface antigen (HBsAg)
Hepatitis C defined as presence of HCV RNA
Known history of HIV
Evidence of significant alcohol consumption
Evidence of drug abuse
Subjects with inadequate response to obeticholic acid (OCA) or intolerance to OCA: OCA must be discontinued 30 days prior to Screening
Use of colchicine, methotrexate, azathioprine, or long-term systemic corticosteroids (\> 2 weeks) within two months prior to Screening
Use of fibrates within 30 days prior to Screening
Use of simvastatin within 7 days prior to Screening
Use of an experimental or unapproved treatment for PBC within 30 days prior to Screening
Use of experimental or unapproved immunosuppressant within 30 days prior to Screening
Treatment with any other investigational therapy or device within 30 days or within five half-lives, whatever is longer, prior to Screening
For females, pregnancy or breast-feeding
Any other condition(s) that would compromise the safety of the subject or compromise the quality of the clinical study, as judged by the investigator

Intervenciones

drug

seladelpar 5-10 mg

Seladelpar 5 mg for 6 months and then titrating up to 10 mg based on tolerability and response for remainder of double-blind period. After completion of the 1-year double-blind period subjects will be offered the opportunity to enter an open label long term safety study. Subjects will continue the seladelpar dose (5 or 10 mg) received during the double-blinded study

drug

seladelpar 10 mg

Seladelpar 10 mg for double-blind period. After completion of the 1-year double-blind period subjects will be offered the opportunity to enter an open label safety study. Subjects will continue the seladelpar dose (10 mg) received during the double-blinded study

drug

Placebo

One capsule daily for double-blind period. After completion of the 1-year double-blind period subjects will be offered the opportunity to enter an open label long term safety study. Subjects on placebo will be re-randomized to initiate seladelpar at 5 or 10 mg once daily

Estudio de fase 3, controlado con placebo, aleatorizado, de 52 semanas para evaluar la seguridad y eficacia de seladelpar en sujetos con colangitis biliar primaria (CBP) y respuesta inadecuada o intolerancia al ácido ursodesoxicólico (AUDC)

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

seladelpar 5-10 mg

seladelpar 10 mg

Placebo

Ubicaciones

Hospital Universitario Austral

Fundación Sanatorio Güemes

Hospital Provincial Del Centenario

DIM Clínica Privada

Patrocinadores