Combination Antiretroviral Therapy (cART) for PBC
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|ClinicalTrials.gov Identifier: NCT03954327|
Recruitment Status : Not yet recruiting
First Posted : May 17, 2019
Last Update Posted : October 3, 2019
|Condition or disease||Intervention/treatment||Phase|
|Primary Biliary Cholangitis||Drug: Emtricitabine (FTC)/Tenofovir Disoproxil (TDF) Drug: Raltegravir Drug: Placebo Oral Capsule [CEBOCAP]||Phase 2|
Greater than 10% difference in mean percentage of alkaline phosphatase (ALP) reduction in cART vs. placebo at 6 and 12 months.
- Serum biochemistries bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) will be studied as continuous variables.
- 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.
- 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.
- 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].
- Serial human betaretrovirus measurement in peripheral blood and cellular immune response to viral peptides.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Randomized Controlled Trail (RCT) of Emtricitabine, Tenofovir Disoproxil and Raltegravir for Patients With Primary Biliary Cholangitis Unresponsive to Ursodeoxycholic Acid (UDCA)|
|Estimated Study Start Date :||February 2020|
|Estimated Primary Completion Date :||November 2022|
|Estimated Study Completion Date :||November 2023|
|Experimental: Emtricitabine (FTC)/Tenofovir Disoproxil (TDF) & Raltegravir||
Drug: Emtricitabine (FTC)/Tenofovir Disoproxil (TDF)
Emtricitabine (FTC) 200 mg/Tenofovir Disoproxil (TDF) 300 mg by mouth once per day
Raltegravir (RTF) 600 mg two tablets by mouth once per day
|Placebo Comparator: Placebo||
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
- Change in alkaline phosphatase levels [ Time Frame: 12 months ]Mean changes in alkaline phosphatase levels after 12 months treatment with combination antiretroviral therapy or placebo.
- Serial changes in alkaline phosphatase [ Time Frame: Evaluation baseline, 3 months, 6 months and end of RCT; then 3 months, 6 monthly to end of open label therapy] ]Serial changes in alkaline phosphatase levels with combination antiretroviral therapy or placebo.
- Serial changes in ALT [ Time Frame: Evaluation baseline, 3 months, 6 months and end of RCT; then 3 months, 6 monthly to end of open label therapy] ]Serial changes in ALT levels with combination antiretroviral therapy or placebo.
- Serial changes in bilirubin [ Time Frame: Evaluation baseline, 3 months, 6 months and end of RCT; then 3 months, 6 monthly to end of open label therapy] ]Serial changes in bilirubin levels with combination antiretroviral therapy or placebo.
- Achievement of the composite biochemistry endpoint [ Time Frame: 6 and 12 months ](i) reduction of ALP to < 1.67 upper limit of normal, (ii) normalization of bilirubin within ULN and (iii) reduction of ALP by > 15%
- Human Betaretrovirus load in peripheral blood [ Time Frame: Evaluation baseline, 3 months, 6 months and end of RCT; then 3 months, 6 monthly to end of open label therapy ]Quantification of Human Betaretrovirus DNA or RNA levels in peripheral blood measured by Quantigene or polymerase chain reaction with therapy or placebo.
- Interferon gamma release to Human Betaretrovirus peptide stimulation [ Time Frame: Evaluation at baseline, 6 months and end of RCT; then 6 monthly to end of open label therapy ]Concentration of interferon gamma released from peripheral blood mononuclear cells stimulated by Human Betaretrovirus peptides in vitro in response to treatment or placebo.
- Liver histology [ Time Frame: Pretreatment biopsy and 24 month biopsy after initiation of study therapy ]Liver histology will be measured in a scale for staging and grading disease using the Nakanuma scoring system. Scores for fibrosis, bile duct loss, and chronic cholestasis will be combined for staging: stage 1, total score of 0; stage 2, score 1-3; stage 3, score 4-6; and stage 4, score 7-9. Cholangitis activity and hepatitis activity will be graded as 0-3, respectively.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03954327
|Contact: Andrew Mason, MDemail@example.com|
|Contact: Breanne Stewart, RNfirstname.lastname@example.org|
|University of Alberta||Not yet recruiting|
|Edmonton, Alberta, Canada, T6G 2R3|
|Contact: Andrew Mason, MD 780-492-8172 email@example.com|
|Contact: Breanne Stewart, RN 780-9748606 firstname.lastname@example.org|
|Sub-Investigator: Aldo Montano Loza, MD|
|Sub-Investigator: Schokrollah Elahi, PhD|
|Canada, British Columbia|
|University of British Columbia||Not yet recruiting|
|Vancouver, British Columbia, Canada, V6Z 2C5|
|Contact: Eric Yoshida, MD email@example.com|
|Sub-Investigator: Vladimir Marquez, MD|
|Sub-Investigator: Hin Hin Ko, MD|
|University of Toronto||Not yet recruiting|
|Toronto, Ontario, Canada, M5S 1A1|
|Contact: Aliya Gulamhusein, MD Aliya.Gulamhusein@uhn.ca|
|Montréal, Quebec, Canada|
|University of Montreal||Not yet recruiting|
|Montréal, Quebec, Canada|
|Contact: Catherine Vincent, MD firstname.lastname@example.org|
|Principal Investigator:||Andrew Mason, MD||University of Alberta|