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Human Immunodeficiency VirusPhase 3CTN289NCT02660905

HIV Drug Switch Followed by HCV Therapy in HIV-HCV Co-Infection

A Phase 3 study testing E/C/F/TAF; and Ledipasvir-Sofosbuvir in people with Human Immunodeficiency Virus and Hepatitis C, Chronic, run by Ottawa Hospital Research Institute at 2 sites in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is an prospective open label pilot study conducted over 32 weeks. A total of 25 eligible participants who are infected with HCV and HIV will be recruited from 2 Canadian HIV Trials Network (CTN) sites (Ottawa Hospital Research Institute and McGill University Health Centre) This study is investigating the… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
E/C/F/TAF; and Ledipasvir-Sofosbuvir
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
2 sitesCanada
Study dates
Apr 2016to Jun 2018
Phase
Phase 3
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

  • HIV infected (ELISA with western blot confirmation)
  • HCV RNA positive for minimum of 6 months / Genotype 1
  • Prescribed cART that may include any Department of Health and Human Services (DHHS) recommended or alternative regimens, which the treating physician considers, is appropriate for their patient. (We anticipate that approximately 60% will be on HIV protease inhibitor-based regimens).
  • HIV RNA BLLQ for minimum of 3 months
  • Stage 3 or 4 fibrosis
  • No evidence of liver decompensation defined as past or current ascites, bleeding varices or hepatic encephalopathy. Prior interferon, ribavirin and/or HCV protease inhibitor exposure will be allowed with the exception of cirrhotic with a past history of null response to interferon-based therapy.
Show all 10Show fewer
  • Ability to remain adherent to medications and study protocol as per investigator opinion
  • For female subjects, not pregnant, planning or suspected to be pregnant or breast-feeding
  • Willing to use acceptable methods of birth control, as defined in protocol
  • Active substance use and/or mental health issues will not be exclusionary assuming other criteria are met. This inclusion will be restricted to those stably housed and engaged in harm reduction strategies. Our intent is to evaluate study participants who are representative of our clinical population and consider 'difficult to cure' compared to populations already evaluated in licensing studies

Who cannot join

  • Concomitant use of drugs with contraindication drug interactions with E/C/F/TAF of SOF-LDV
  • History of HIV integrase inhibitors or NRTI resistance mutations
  • Platelets <50 x10^9/L

Trial locations and contacts

2 sites in 1 country.

Canada2 sites

  • The Research Institute of the McGill University Health Centre

    Montreal, Quebec, H4A 3J1

  • The Ottawa Hospital, General Campus

    Ottawa, Ontario

Other trials in Canada

About this study

Official title: Evaluation of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (ECF/TAF) Switch Followed by Ledipasvir-Sofosbuvir HCV Therapy in HIV-HCV Co-Infection: A CIHR Canadian HIV Trials Network-Gilead Pilot Trial Proposal

This is an prospective open label pilot study conducted over 32 weeks.

A total of 25 eligible participants who are infected with HCV and HIV will be recruited from 2 Canadian HIV Trials Network (CTN) sites (Ottawa Hospital Research Institute and McGill University Health Centre)

Read more

This study is investigating the effectiveness of a combination of Elvitegravir/Cobicistat/Emtricitabine/ Tenofovir Alafenamide Single Tablet Regimen (E/C/F/TAF STR) for HIV treatment and Harvoni for HCV treatment.

This study will assess the effect that the study drug has on the metabolism of sugar, the changes in fat in the bloodstream, and other metabolic changes. Metabolism is the process your body uses to get or make energy from the food you eat.

This study may provide information on the impact of liver fibrosis (scarring of liver tissues) on metabolic changes before, during and after HCV antiviral therapy.

Drug-drug interactions (DDI) between E/C/F/TAF and LPV-SOF have been well evaluated and no clinically significant interactions have been identified.

A switch to E/C/F/TAF in the context of LPV-SOF HCV antiviral treatment preparation may be particularly beneficial because of its:

  1. favorable side effect profile
  2. once daily STR formulation
  3. known DDI profile with LPV-SOF
  4. neutral effect on liver fibrosis
  5. improved kidney and bone safety profile with the use of TAF

Conduct of this study is justified as it:

  1. Assesses a minimal pill count and dosing frequency strategy of co-treatment of HIV and HCV using well tolerated medications with an excellent safety profile and known DDI profile.
  2. Provides additional safety data for TAF in the HIV-HCV co-infected population.
  3. Quantifies adherence and identifies obstacles to full adherence in this population. There is a paucity of data related to DAA adherence in licensing studies.
  4. Provides real-world safety and efficacy data to support the public funding for LPV-SOF DAA therapy in HIV-HCV co-infected populations.
  5. Provides preliminary data on the immunologic and metabolic consequences of HCV clearance in HIV-HCV co-infection
  6. As a pilot study, the information gathered will inform the feasibility of future clinical trials evaluating novel treatment strategies for HIV-HCV co-infected patients.
Read the detailed description

The availability of interferon (IFN)-free HCV Direct Acting Antiviral (DAA) antiviral therapy such as Ledipasvir-Sofosbuvir (LPV-SOF) allows for broad provision of treatment for populations living with HIV-HCV. Co-infected persons frequently have competing co-morbidities and are at risk for progressive liver disease which makes adherence and combined management of HIV and HCV challenging. Simple, safe, well tolerated regimens with few drug-drug interactions could be highly beneficial in ensuring success of HCV therapy in this population. With this is mind, the optimal management of antiretroviral therapy prior to initiating LPV-SOF treatment remains unclear.

E/C/F/TAF [elvitegravir-cobicistat-emtricitabine-tenofovir alafenamide fumarate (TAF)] will be assessed in this study because it is formulated as a single tablet which facilitates adherence by once daily dosing and reduced pill count. It is established to be affective at achieving and maintaining HIV virologic suppression. The safety profile of this HIV regimen is excellent. The E/C/F/TAF formulation assessed in this study will contain TAF. This formulation has been evaluated in HIV-infected populations and found to be of equivalent HIV antiviral activity and to have improved impact on renal and bone metabolism [ref: David Wohl, Anton Pozniak, Melanie Thompson, Edwin DeJesus, Daniel Podzamczer, Jean-Michel Molina, Gordon Crofoot, Christian Callebaut, Hal Martin, Scott McCallister. Tenofovir Alafenamide (TAF) in a Single-Tablet Regimen in Initial HIV-1 Therapy. Conference on Retroviruses and Opportunistic Infections. 113LB. February 23-26, 2015, Seattle, Washington.]. There is minimal safety data in HIV-HCV co-infection.

Drug-drug interactions (DDI) between HIV antiretrovirals and HCV antivirals remain a key obstacle to the safe and effective delivery. The DDI between E/C/F/TAF and LPV-SOF have been well evaluated and no clinically significant interactions have been identified.

A switch to E/C/F/TAF in the context of LPV-SOF HCV antiviral treatment preparation may be particularly beneficial because of its:

  1. favorable side effect profile
  2. once daily STR formulation
  3. known DDI profile with LPV-SOF
  4. neutral effect on liver fibrosis
  5. improved kidney and bone safety profile with the use of TAF

Conduct of this study is justified as it:

  1. Assesses a minimal pill count and dosing frequency strategy of co-treatment of HIV and HCV using well tolerated medications with an excellent safety profile and known DDI profile (Complera followed by LPV-SOF). Polypharmacy in the co-infected population remains a significant challenge to therapeutic success.
  2. Provides additional safety data for TAF in the HIV-HCV co-infected population.
  3. Quantifies adherence and identifies obstacles to full adherence in this population. There is a paucity of data related to DAA adherence in licensing studies.
  4. Provides real-world safety and efficacy data to support the public funding for LPV-SOF DAA therapy in HIV-HCV co-infected populations.
  5. Provides preliminary data on the immunologic and metabolic consequences of HCV clearance in HIV-HCV co-infection
  6. As a pilot study, the information gathered will inform the feasibility of future clinical trials evaluating novel treatment strategies for HIV-HCV co-infected patients.
Being tested
E/C/F/TAF;, Ledipasvir-Sofosbuvir
Keywords
HIV-HCV co-infected, HCV, HIV, Hep C, Hepatitis C, HCV positive
Medical subject headings
Acquired Immunodeficiency Syndrome, Hepatitis C, Chronic, Hepatitis C

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • E/C/F/TAF;Drug

    Also called Genvoya, emtricitabine/ rilpivirine/ tenofovir disoproxil fumarate

    Evaluation of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Switch followed by Ledipasvir-Sofosbuvir Antiviral HCV Therapy

  • Ledipasvir-SofosbuvirDrug

    Also called Harvoni

    Evaluation of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Switch followed by Ledipasvir-Sofosbuvir Antiviral HCV Therapy

Study groups in NCT02660905
Study groupRoleWhat they receive
Active TreatmentExperimentalE/C/F/TAF Ledipasvir-Sofosbuvir/TAF
Receives: Drug: E/C/F/TAF;; Drug: Ledipasvir-Sofosbuvir

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Proportion of approached patients who agreed to switch from their current Antiretroviral (ARV) regimen and be screened for this study

    Number of patients

    Measured: 52 weeks

Secondary outcomes (4)

  1. Proportion of subjects achieving SVR12

    HCV RNA at 12 weeks post HCV treatment completion

    Measured: 24 weeks

  2. Proportion of subjects maintaining undetectable HIV RNA levels

    HIV RNA below detection throughout study period

    Measured: 32 weeks

  3. Proportion of subjects initiating HCV antiviral therapy

    Number of participants

    Measured: 4 weeks

  4. Proportion of subjects discontinuing study medications due to adverse events

    Liver enzyme abnormalities

    Measured: 32 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jan 2016 (estimated)
  2. Study startApr 2016
  3. Primary completionJan 2018
  4. Study completionJun 2018

Resources

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 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02660905
Sponsor's protocol ID
20150881-01H
Acronym
CTN289
Status last verified
Mar 2019
First submitted
21 Oct 2015
Last updated
14 Nov 2022
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Allison ME, Wreghitt T, Palmer CR, Alexander GJ. Evidence for a link between hepatitis C virus infection and diabetes mellitus in a cirrhotic population. J Hepatol. 1994 Dec;21(6):1135-9. doi: 10.1016/s0168-8278(05)80631-2.

    PubMed 7699240

  • Mavrogiannaki A, Karamanos B, Manesis EK, Papatheodoridis GV, Koskinas J, Archimandritis AJ. Prevalence of glucose intolerance in patients with chronic hepatitis B or C: a prospective case-control study. J Viral Hepat. 2009 Jun;16(6):430-6. doi: 10.1111/j.1365-2893.2009.01077.x. Epub 2009 Feb 6.

    PubMed 19200136

  • Grasso A, Malfatti F, De Leo P, Martines H, Fabris P, Toscanini F, Anselmo M, Menardo G. Insulin resistance predicts rapid virological response in non-diabetic, non-cirrhotic genotype 1 HCV patients treated with peginterferon alpha-2b plus ribavirin. J Hepatol. 2009 Dec;51(6):984-90. doi: 10.1016/j.jhep.2009.07.008. Epub 2009 Jul 23.

    PubMed 19695729

  • Poustchi H, Negro F, Hui J, Cua IH, Brandt LR, Kench JG, George J. Insulin resistance and response to therapy in patients infected with chronic hepatitis C virus genotypes 2 and 3. J Hepatol. 2008 Jan;48(1):28-34. doi: 10.1016/j.jhep.2007.07.026. Epub 2007 Oct 1.

    PubMed 17977612

  • Taura N, Ichikawa T, Hamasaki K, Nakao K, Nishimura D, Goto T, Fukuta M, Kawashimo H, Fujimoto M, Kusumoto K, Motoyoshi Y, Shibata H, Abiru N, Yamasaki H, Eguchi K. Association between liver fibrosis and insulin sensitivity in chronic hepatitis C patients. Am J Gastroenterol. 2006 Dec;101(12):2752-9. doi: 10.1111/j.1572-0241.2006.00835.x. Epub 2006 Oct 6.

    PubMed 17026566

  • Hung CH, Wang JH, Hu TH, Chen CH, Chang KC, Yen YH, Kuo YH, Tsai MC, Lu SN, Lee CM. Insulin resistance is associated with hepatocellular carcinoma in chronic hepatitis C infection. World J Gastroenterol. 2010 May 14;16(18):2265-71. doi: 10.3748/wjg.v16.i18.2265.

    PubMed 20458764

  • Baid S, Cosimi AB, Farrell ML, Schoenfeld DA, Feng S, Chung RT, Tolkoff-Rubin N, Pascual M. Posttransplant diabetes mellitus in liver transplant recipients: risk factors, temporal relationship with hepatitis C virus allograft hepatitis, and impact on mortality. Transplantation. 2001 Sep 27;72(6):1066-72. doi: 10.1097/00007890-200109270-00015.

    PubMed 11579302

  • Butt AA, Xiaoqiang W, Budoff M, Leaf D, Kuller LH, Justice AC. Hepatitis C virus infection and the risk of coronary disease. Clin Infect Dis. 2009 Jul 15;49(2):225-32. doi: 10.1086/599371.

    PubMed 19508169

  • Donadon V, Balbi M, Ghersetti M, Grazioli S, Perciaccante A, Della Valentina G, Gardenal R, Dal Mas M, Casarin P, Zanette G, Miranda C. Antidiabetic therapy and increased risk of hepatocellular carcinoma in chronic liver disease. World J Gastroenterol. 2009 May 28;15(20):2506-11. doi: 10.3748/wjg.15.2506.

    PubMed 19469001

  • Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM; Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002 Feb 7;346(6):393-403. doi: 10.1056/NEJMoa012512.

    PubMed 11832527

  • Dai CY, Chuang WL, Ho CK, Hsieh MY, Huang JF, Lee LP, Hou NJ, Lin ZY, Chen SC, Hsieh MY, Wang LY, Tsai JF, Chang WY, Yu ML. Associations between hepatitis C viremia and low serum triglyceride and cholesterol levels: a community-based study. J Hepatol. 2008 Jul;49(1):9-16. doi: 10.1016/j.jhep.2008.03.016. Epub 2008 Apr 22.

    PubMed 18486265

  • Economou M, Milionis H, Filis S, Baltayiannis G, Christou L, Elisaf M, Tsianos E. Baseline cholesterol is associated with the response to antiviral therapy in chronic hepatitis C. J Gastroenterol Hepatol. 2008 Apr;23(4):586-91. doi: 10.1111/j.1440-1746.2007.04911.x. Epub 2007 May 13.

    PubMed 17498221

  • Petit JM, Benichou M, Duvillard L, Jooste V, Bour JB, Minello A, Verges B, Brun JM, Gambert P, Hillon P. Hepatitis C virus-associated hypobetalipoproteinemia is correlated with plasma viral load, steatosis, and liver fibrosis. Am J Gastroenterol. 2003 May;98(5):1150-4. doi: 10.1111/j.1572-0241.2003.07402.x.

    PubMed 12809841

  • Siagris D, Christofidou M, Theocharis GJ, Pagoni N, Papadimitriou C, Lekkou A, Thomopoulos K, Starakis I, Tsamandas AC, Labropoulou-Karatza C. Serum lipid pattern in chronic hepatitis C: histological and virological correlations. J Viral Hepat. 2006 Jan;13(1):56-61. doi: 10.1111/j.1365-2893.2005.00655.x.

    PubMed 16364083

  • Corey KE, Kane E, Munroe C, Barlow LL, Zheng H, Chung RT. Hepatitis C virus infection and its clearance alter circulating lipids: implications for long-term follow-up. Hepatology. 2009 Oct;50(4):1030-7. doi: 10.1002/hep.23219.

    PubMed 19787818

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing E/C/F/TAF; and Ledipasvir-Sofosbuvir in people with Human Immunodeficiency Virus and Hepatitis C, Chronic, run by Ottawa Hospital Research Institute at 2 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 10 inclusion and 3 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 14 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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?

Proportion of approached patients who agreed to switch from their current Antiretroviral (ARV) regimen and be screened for this study (time frame: 52 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02660905, which also lists 23 linked publications.

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 14 Nov 2022.

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