Primary Biliary CholangitisPhase 2NCT03954327
Combination Antiretroviral Therapy (cART) for PBC
A Phase 2 study testing Emtricitabine (FTC)/Tenofovir Disoproxil (TDF) and Raltegravir in people with Primary Biliary Cholangitis, run by University of Alberta at 6 sites in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Primary Biliary Cholangitis
- What is being tested?
- Emtricitabine (FTC)/Tenofovir Disoproxil (TDF) and Raltegravir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 37 participants
- Where
- 6 sitesCanada
- Study dates
- 1 Mar 2021to 1 Jan 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- subjects with baseline total bilirubin > 2 x ULN,(patients meeting inclusion criteria stabilized on second line therapies including obeticholic acid or bezafibrate over 12 months or more may be enrolled).
- 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 ;
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- 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.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Canada6 sites
University of Alberta
Edmonton, Alberta, T6G 2R3
University of Montreal
Montreal, Quebec
Royal University Hospital
Saskatoon, Saskatchewan, S7N 0W8
University of Toronto
Toronto, Ontario, M5S 1A1
St Paul's Hospital, University of British Columbia
Vancouver, British Columbia, V6Z 1Y6
Vancouver General Hospital, University of Brittish Columbia
Vancouver, British Columbia, V6Z 1Z4
About this study
Official title: Randomized Controlled Trail (RCT) of Emtricitabine, Tenofovir Disoproxil and Raltegravir for Patients With Primary Biliary Cholangitis Unresponsive to Ursodeoxycholic Acid (UDCA)
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.
Read the detailed description
Primary endpoint:
Change in mean percentage of alkaline phosphatase (ALP) reduction in cART vs. placebo at 6 and 12 months.
Secondary endpoints:
- 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.
- Conditions
- Primary Biliary Cholangitis
- Being tested
- Emtricitabine (FTC)/Tenofovir Disoproxil (TDF), Raltegravir, Placebo Oral Capsule [CEBOCAP]
- Medical subject headings
- Liver Cirrhosis, Biliary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Emtricitabine (FTC)/Tenofovir Disoproxil (TDF)Drug
Also called Truvada
Emtricitabine (FTC) 200 mg/Tenofovir Disoproxil (TDF) 300 mg by mouth once per day
RaltegravirDrug
Also called Isentress
Raltegravir (RTF) 600 mg two tablets by mouth once per day
Placebo Oral Capsule [CEBOCAP]Drug
Also called placebo
Two capsules identical to Raltegravir and one capsule identical to Truvada with no active ingredients by mouth once per day
| Study group | Role | What they receive |
|---|---|---|
| Emtricitabine (FTC)/Tenofovir Disoproxil (TDF) & Raltegravir | Experimental | one Emtricitabine 200mg and Tenofovir Disoproxil 300mg tablet two Raltegravir 600mg tablets Receives: Drug: Emtricitabine (FTC)/Tenofovir Disoproxil (TDF); Drug: Raltegravir |
| Placebo | Placebo comparator | Identical tablets resembling one Emtricitabine 200mg and Tenofovir Disoproxil 300mg tablet two Raltegravir 600mg tablets Receives: Drug: Placebo Oral Capsule [CEBOCAP] |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in alkaline phosphatase levels
Mean changes in alkaline phosphatase levels after 12 months treatment with combination antiretroviral therapy or placebo.
Measured: 12 months
Secondary outcomes (7)
Serial changes in alkaline phosphatase
Serial changes in alkaline phosphatase levels with combination antiretroviral therapy or placebo.
Measured: 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
Serial changes in ALT levels with combination antiretroviral therapy or placebo.
Measured: 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
Serial changes in bilirubin levels with combination antiretroviral therapy or placebo.
Measured: Evaluation baseline, 3 months, 6 months and end of RCT; then 3 months, 6 monthly to end of open label therapy]
Achievement of the composite biochemistry endpoint
(i) reduction of ALP to < 1.67 upper limit of normal, (ii) normalization of bilirubin within ULN and (iii) reduction of ALP by > 15%
Measured: 6 and 12 months
Human Betaretrovirus load in peripheral blood
Quantification of Human Betaretrovirus DNA or RNA levels in peripheral blood measured by Quantigene or polymerase chain reaction with therapy or placebo.
Measured: Evaluation baseline, 3 months, 6 months and end of RCT; then 3 months, 6 monthly to end of open label therapy
Interferon gamma release to Human Betaretrovirus peptide stimulation
Concentration of interferon gamma released from peripheral blood mononuclear cells stimulated by Human Betaretrovirus peptides in vitro in response to treatment or placebo.
Measured: Evaluation at baseline, 6 months and end of RCT; then 6 monthly to end of open label therapy
Liver histology
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.
Measured: Pretreatment biopsy and 24 month biopsy after initiation of study therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2019
- Study start1 Mar 2021
- Primary completion1 Oct 2022
- Study completion1 Jan 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary Biliary CholangitisStudies of the same condition, open and under way.
- More trials run by University of AlbertaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alberta
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Andrew Mason, MD, Principal investigator, University of Alberta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03954327
- Sponsor's protocol ID
- Pro00082571
- Status last verified
- Feb 2024
- First submitted
- 7 May 2019
- Last updated
- 16 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Controlled Trail (RCT) of Emtricitabine, Tenofovir Disoproxil and Raltegravir for Patients With Primary Biliary Cholangitis Unresponsive to Ursodeoxycholic Acid (UDCA)
- ClinicalTrials.gov ID
- NCT03954327
- Acronym / sponsor ID
- Pro00082571
- Conditions
- Primary Biliary Cholangitis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- University of AlbertaUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 1 Mar 2021 (actual)
- Primary completion
- 1 Oct 2022 (actual)
- Study completion
- 1 Jan 2024 (actual)
- First posted
- 17 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Emtricitabine (FTC)/Tenofovir Disoproxil (TDF) & Raltegravir | Experimental | Drug: Emtricitabine (FTC)/Tenofovir Disoproxil (TDF), Drug: Raltegravirone Emtricitabine 200mg and Tenofovir Disoproxil 300mg tablet two Raltegravir 600mg tablets |
| Placebo | Placebo comparator | Drug: Placebo Oral Capsule [CEBOCAP]Identical tablets resembling one Emtricitabine 200mg and Tenofovir Disoproxil 300mg tablet two Raltegravir 600mg tablets |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (9 listed)
- subjects with baseline total bilirubin > 2 x ULN,(patients meeting inclusion criteria stabilized on second line therapies including obeticholic acid or bezafibrate over 12 months or more may be enrolled).
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Emtricitabine (FTC)/Tenofovir Disoproxil (TDF)Also: TruvadaEmtricitabine (FTC) 200 mg/Tenofovir Disoproxil (TDF) 300 mg by mouth once per day | Drug | Emtricitabine (FTC)/Tenofovir Disoproxil (TDF) & Raltegravir |
| RaltegravirAlso: IsentressRaltegravir (RTF) 600 mg two tablets by mouth once per day | Drug | Emtricitabine (FTC)/Tenofovir Disoproxil (TDF) & Raltegravir |
| Placebo Oral Capsule [CEBOCAP]Also: placeboTwo capsules identical to Raltegravir and one capsule identical to Truvada with no active ingredients by mouth once per day | Drug | Placebo |
Primary outcome
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.
7 secondary outcomes
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 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 bilirubin
Time frame: Evaluation baseline, 3 months, 6 months and end of RCT; then 3 months, 6 monthly to end of open label therapy]
Achievement of the composite biochemistry endpoint
Time frame: 6 and 12 months
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
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
Liver histology
Time frame: Pretreatment biopsy and 24 month biopsy after initiation of study therapy
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Feb 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrew Mason, MD principal investigator
University of Alberta
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Emtricitabine (FTC)/Tenofovir Disoproxil (TDF) and Raltegravir in people with Primary Biliary Cholangitis, run by University of Alberta at 6 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in alkaline phosphatase levels (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Feb 2024.