Combination Antiretroviral Therapy (cART) for PBC

NCT ID: NCT03954327

Last Updated: 2024-02-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-01
• Study Completion Date: 2024-01-01

Brief Summary

Placebo Controlled, double-blind randomized controlled trial (RCT) with 12 months Tenofovir Disoproxil and Raltegravir for primary biliary cholangitis (PBC) patients unresponsive to Ursodeoxycholic Acid (UDCA). Placebo patients will be offered 12 months open label therapy at unblinding. All patients will be offered an additional 12 months open label therapy. Observational, open label study will be performed in parallel using Emtricitabine (FTC)/Tenofovir Disoproxil (TDF) & Raltegravir in liver transplant recipients meeting all entry criteria except for use of immunosuppression.

Detailed Description

Primary endpoint:

Change in mean percentage of alkaline phosphatase (ALP) reduction in cART vs. placebo at 6 and 12 months.

Secondary endpoints:

1. Serum biochemistries bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) will be studied as continuous variables.

2. Composite endpoint used for the POISE study [A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis]: (i) reduction of ALP to < 1.67 upper limit of normal, (ii) normalization of bilirubin within upper limit of normal (ULN) and (iii) reduction of ALP by > 15% at 6 and 12 months.

3. Symptomatic evaluation performed using the PBC-40 to assess five symptom domains relating to fatigue, itch, cognitive symptoms, social and emotional symptoms, and other symptoms.

4. Histological change in grade and stage of PBC using the Nakanuma scoring system for a subgroup of patients undergoing liver biopsy [liver biopsy not compulsory for study].

5. Serial human betaretrovirus measurement in peripheral blood and cellular immune response to viral peptides.

Conditions

Primary Biliary Cholangitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Emtricitabine (FTC)/Tenofovir Disoproxil (TDF) & Raltegravir

one Emtricitabine 200mg and Tenofovir Disoproxil 300mg tablet two Raltegravir 600mg tablets

Group Type: EXPERIMENTAL

Emtricitabine (FTC)/Tenofovir Disoproxil (TDF)

Intervention Type: DRUG

Emtricitabine (FTC) 200 mg/Tenofovir Disoproxil (TDF) 300 mg by mouth once per day

Raltegravir

Intervention Type: DRUG

Raltegravir (RTF) 600 mg two tablets by mouth once per day

Placebo

Identical tablets resembling one Emtricitabine 200mg and Tenofovir Disoproxil 300mg tablet two Raltegravir 600mg tablets

Group Type: PLACEBO_COMPARATOR

Placebo Oral Capsule [CEBOCAP]

Intervention Type: DRUG

Two capsules identical to Raltegravir and one capsule identical to Truvada with no active ingredients by mouth once per day

Interventions

Emtricitabine (FTC)/Tenofovir Disoproxil (TDF)

Emtricitabine (FTC) 200 mg/Tenofovir Disoproxil (TDF) 300 mg by mouth once per day

Intervention Type: DRUG

Raltegravir

Raltegravir (RTF) 600 mg two tablets by mouth once per day

Intervention Type: DRUG

Placebo Oral Capsule [CEBOCAP]

Two capsules identical to Raltegravir and one capsule identical to Truvada with no active ingredients by mouth once per day

Intervention Type: DRUG

Other Intervention Names

Truvada; Isentress; placebo

Eligibility Criteria

Inclusion Criteria

• over 18 years old of either sex,
• Anti-mitochondrial antibody +ve or liver histology compatible with PBC,
• stable UDCA dose of 13-15 mg/kg for > 12 months or intolerant to UDCA,
• ALP at least 1.67 x ULN or abnormal bilirubin less than 2x ULN
• able to read and sign informed consent form.

• use of non-standard or experimental therapy within the last 6 months,
• advanced liver disease: INR > 1.2 ULN, Albumin < 35 g/L lower limit of normal, platelets < 120,000/microL unless varices with risk of bleeding excluded by endoscopy within the last 6 months, Childs Pugh class B or C cirrhosis, presence of grade 2 varices or previous variceal hemorrhage, encephalopathy, ascites or need for liver transplantation within the next two years;
• secondary diagnosis such as HIV, viral hepatitis, drug induced liver injury, extrahepatic biliary obstruction, primary sclerosing cholangitis, metabolic liver - regular use of > 30g alcohol/day in the last year;
• a predicted survival of less than 3 years from malignant or other life threatening disease;
• hepatic mass consistent with hepatocellular carcinoma ;
• previous allergic reaction to study medications;
• Glomerular Filtration Rate less than < 30 mL/min as measured Cockcroft-Gault formula;
• pregnancy, breast-feeding or pre-menopausal patients not using contraception.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

University of Alberta

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Andrew Mason, MD

Role: PRINCIPAL_INVESTIGATOR

University of Alberta

Locations

University of Alberta

Edmonton, Alberta, Canada

St Paul's Hospital, University of British Columbia

Vancouver, British Columbia, Canada

Vancouver General Hospital, University of Brittish Columbia

Vancouver, British Columbia, Canada

University of Toronto

Toronto, Ontario, Canada

University of Montreal

Montreal, Quebec, Canada

Royal University Hospital

Saskatoon, Saskatchewan, Canada

Countries

Canada

Other Identifiers

Pro00082571

Identifier Type: -

Identifier Source: org_study_id