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

NCT02660905 | Completed Phase 3 DMC

• 1 other identifier: 20150881-01H
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 2

Brief 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 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. 1.favorable side effect profile
2. 2.once daily STR formulation
3. 3.known DDI profile with LPV-SOF
4. 4.neutral effect on liver fibrosis
5. 5.improved kidney and bone safety profile with the use of TAF
6. 6.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.
7. 7.Provides additional safety data for TAF in the HIV-HCV co-infected population.
8. 8.Quantifies adherence and identifies obstacles to full adherence in this population. There is a paucity of data related to DAA adherence in licensing studies.
9. 9.Provides real-world safety and efficacy data to support the public funding for LPV-SOF DAA therapy in HIV-HCV co-infected populations.
10. 10.Provides preliminary data on the immunologic and metabolic consequences of HCV clearance in HIV-HCV co-infection
11. 11.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.

Conditions

Human Immunodeficiency Virus; Hepatitis C, Chronic

Keywords

HIV-HCV co-infected; HCV; HIV; Hep C; Hepatitis C; HCV positive

Outcome Measures

Primary Outcomes (1)

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

  Number of patients

  52 weeks

Secondary Outcomes (4)

• Proportion of subjects achieving SVR12

  24 weeks

• Proportion of subjects maintaining undetectable HIV RNA levels

  32 weeks

• Proportion of subjects initiating HCV antiviral therapy

  4 weeks

• Proportion of subjects discontinuing study medications due to adverse events

  32 weeks

Other Outcomes (10)

• Measures of fibrosis will be assessed over the duration of the study.

  32 weeks

• Measures of serial cellular immune will be assessed over the duration of the study.

  32 weeks

• Measures of serial cytokine immune function will be assessed over the duration of the study.

  32 weeks

Study Arms (1)

Active Treatment

EXPERIMENTAL

E/C/F/TAF Ledipasvir-Sofosbuvir/TAF

Drug: E/C/F/TAF;; Drug: Ledipasvir-Sofosbuvir

Interventions

E/C/F/TAF; DRUG

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

Also known as: Genvoya, emtricitabine/ rilpivirine/ tenofovir disoproxil fumarate

Active Treatment

Ledipasvir-Sofosbuvir DRUG

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

Also known as: Harvoni

Active Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead
• Gilead Sciences: collaborator
• CIHR Canadian HIV Trials Network: collaborator

Study Sites (2)

The Ottawa Hospital, General Campus

Ottawa, Ontario, Canada

Location

The Research Institute of the McGill University Health Centre

Montreal, Quebec, H4A 3J1, Canada

Location

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MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Hepatitis C, Chronic; Hepatitis C

Interventions

Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Emtricitabine; Rilpivirine; Tenofovir; ledipasvir, sofosbuvir drug combination

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Hepatitis, Viral, Human; Flaviviridae Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cobicistat; Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Organophosphonates; Organophosphorus Compounds; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations; Nitriles

Study Officials

• Curtis Cooper, MD, FRCPC

  The Ottawa Hospital; Ottawa Hospital Research Institute

  PRINCIPAL INVESTIGATOR

• Marina Klein, MD

  McGill University Health Centre/Research Institute of the McGill University Health Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2015
• First Posted: January 21, 2016
• Study Start: April 1, 2016
• Primary Completion: January 1, 2018
• Study Completion: June 1, 2018
• Last Updated: November 14, 2022

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2)