HIVPhase 4STOP-CONCT02533934

Sofosbuvir Based DAA Therapy in HIV/HCV Coinfected Pre or Post Liver Transplant

A Phase 4 study testing Harvoni in people with HIV and Hepatitis C, run by University of California, San Francisco at 8 sites in United States.

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

Retrospective/Prospective, open-label study using sofosbuvir based DAA therapy to treat HIV/HCV coinfected pre or post liver transplant participants Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: HIV, Hepatitis C, Cirrhosis
What is being tested?: Harvoni
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 68 participants
Where: 8 sitesUnited States
Study dates: Aug 2016to 31 Dec 2019
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 of age at screening
Female participants of child bearing potential must have a negative urine pregnancy test at day 0 prior to dosing.
Has received a liver transplant for HCV or has decompensated cirrhosis (Child's Pugh score of 7 or greater)
Have HIV-1 infection and either:
On HIV medications (antiretrovirals) for at least 4 weeks WITH
An HIV viral load less than the level of detection OR

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On no HIV medications for at least 8 weeks WITH:
A CD4 count of 500 cells/mm3 or more OR
HIV viral load of < 500 copies/mL with a stable CD4 count for at least 3 months
Chronic HCV infection as documented by at least one measurement of plasma HCV RNA >= 1,000 IU/mL during screening and at least one of the following:
A positive anti-HCV antibody, HCV RNA, or an HCV genotype test at least 12 months prior to baseline (Day 0) visit together with positive HCV RNA test
HCV genotype 1, 4, 5 or 6
The use of an anti-HCV positive donor is allowed for participants who have detectable HCV RNA at the time of transplant.
The use of an HIV+ donor is allowed if the participant is enrolled in an IRB approved HOPE Act protocol at the transplant site. If the HIV+ donor is also HCV co-infected, then the recipient must have detectable HCV RNA at the time of transplant.
Able to effectively communicate with the Investigator and other center personnel.
Willing to give written informed consent and comply with the study restrictions and requirements.
Willingness to allow stored blood or tissue samples to be used in the future for studying liver disease and immune function.
Willingness to permit HLA typing to be performed.
Have a transplant team available for all primary and transplant-related care.
If not yet transplanted: expected to be at least 12 weeks prior to transplant in order to complete treatment course.
If not yet transplanted: Must have prior standard of care liver staging consistent with F4.
If not yet transplanted: For pre-LT patients with HCC, they must meet Milan criteria at time of enrollment to be eligible
If post-liver transplant, must be at least 1 month since transplant procedure to begin treatment.
If post-liver transplant, liver disease staging must be documented within the prior year by standard of care methods of liver staging

Who cannot join

Positive HBsAg at screening.
History of any other clinically active chronic liver disease (e.g., hemochromatosis, autoimmune hepatitis, Wilson's disease, >=1 antitrypsin deficiency, alcoholic liver disease, and toxin exposures).
Treatment with unlicensed herbal/natural remedies suggested to be taken for hepatitis treatment, such as Milk thistle, St. Johns Wort or Cats Claw, within 28 days of start of treatment
Treatment with IFN, RBV, telaprevir or boceprevir or any other approved or experimental medication with known anti-HCV activity within 1 month prior to screening date
Any prior exposure to an HCV NS5a specific inhibitor
A personal history of or first degree relative with a history of Torsade de pointes.

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Abnormal hematological and biochemical parameters, including:
Hemoglobin < 8g/dL
Estimated GFR, calculated by the CKD-EPI equation, <30 mL/min/ per 1.73 m2
Sodium <120 mmol/L
History of major organ transplantation other than liver or kidney transplantation.
Difficulty with blood collection/poor venous access for phlebotomy that would prevent the collection of study required samples
Infection requiring systemic antibiotics at the time of screening
Active or recent history (≤ 6 months) of drug or alcohol abuse
Gastrointestinal disorder or post-operative condition that could interfere with the absorption of the study drug.
Donation or loss of more than 400 mL blood within 8 weeks prior to first dose administration.
Any medications prohibited (see table 2 in section 8.11) within 28 days prior to Day 0 visit and likely required during study treatment period
History of clinically significant drug allergy to nucleoside/nucleotide analogs.
History or current evidence of psychiatric illness, endocrine, immunologic disorder, pulmonary, cardiac disease, seizure disorder, cancer or other conditions that in the opinion of the investigator makes the patient unsuitable for the study. Chronic medical conditions, especially if treated with medications (such as hypertension), must be stable at the time of screening. No new therapies should be started within 28 days prior to the study that may confound the assessment of study drug safety.
Participation in a clinical study (other than an IRB approved HOPE Act protocol involving the utilization of an HIV+ donor) in which an investigational drug, biologic, or device was received within 12 weeks prior to first dose administration.
Pregnant/Breastfeeding women

Trial locations and contacts

8 sites in 1 country.

City, postcode or hospital

8 sites in 1 country

United States8 sites

University of Maryland
Baltimore, Maryland, 21201
Johns Hopkins Medical Center
Baltimore, Maryland, 21287
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
Mt. Sinai Medical Center
New York, New York, 10029
Columbia University
New York, New York, 10032
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
University of California, San Francisco
San Francisco, California, 94143
Georgetown University
Washington D.C., District of Columbia, 20057

Other trials in United States

About this study

Official title: A Retrospective/Prospective Cohort Study to Assess Safety, Tolerability, and Efficacy of Sofosbuvir Based Direct Acting Antiviral (DAA) Therapy for Hepatitis C Treatment in HIV/HCV Coinfected Subjects Pre or Post Liver Transplant

Retrospective/Prospective, open-label study using sofosbuvir based DAA therapy to treat HIV/HCV coinfected pre or post liver transplant participants

Read the detailed description

Approximately fifty HIV/HCV coinfected patients with decompensated liver disease will be enrolled in the study. Ten (up to twenty) subjects will be treated with FDC SOF/LDV pre or post liver transplant and followed prospectively. Forty + subjects will be enrolled retrospectively with the intent to capture all patients who have been exposed to sofosbuvir based DAA therapies at participating sites since 1/2014, and to mirror the population being enrolled prospectively.

In addition, participants in the retrospective arm will be contacted to consent to one prospective study visit for liver staging to determine rates of reversal of decompensation, reversal of cirrhosis and improvements in graft survival post treatment, and for future contact by the NIH Clinical Center to assess longer term outcomes when this study ends.

Conditions: HIV, Hepatitis C, Cirrhosis
Being tested: Harvoni
Keywords: HIV, Hepatitis C, Liver Disease, HCV Treatment, transplant
Medical subject headings: Hepatitis C, Fibrosis, Liver Diseases

What participants receive

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

HarvoniDrug
Also called SOF/LDV
Treatment of Hepatitis C with sofosbuvir based HCC therapy

Study groups in NCT02533934
Study group	Role	What they receive
Treatment with Sofosbuvir based HCV Therapy	Experimental	Prospective and retrospective treatment for HCV Receives: Drug: Harvoni

What is being measured

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

Number of Participants With Sustained Virologic Response (SVR)
Sustained virologic response (SVR) defined by hepatitis C virus (HCV) RNA less than the lower level limit of quantification (LLOQ) of <15 IU/ml at a median time of 38.5 months after the end of sofosbuvir-based direct-acting antiviral (DAA) therapy
Measured: Median time from end of treatment was 38.5 months

Secondary outcomes (4)

Reversal in Decompensation
Number of participants with an improved, worsened or unchanged MELD (Model for End-stage Liver Disease) score. A MELD score ranges from 6 to 40. The higher the number, the worse the liver disease.
Measured: Median months from baseline to last MELD measurement is 48 months
Change in Liver Fibrosis
Change in AST to Platelet Ratio Index (APRI) where negative values indicate improvement in liver fibrosis score and positive values indicate worsening of fibrosis score. There is no upper or lower limit for change.
Change in Fibrosis-4 (FIB-4) where negative values indicate improvement in liver fibrosis score and positive values indicate worsening of fibrosis score. There is no upper or lower limit for change.
Measured: Median months from baseline to last APRI measurement is 41 months Median months from baseline to last FIB-4 measurement is 41 months
HIV Viral Breakthrough or Relapse
Number of participants with a detectable HIV viral load after sofosbuvir-based HCV therapy
Measured: Median months from baseline to last HIV follow-up is 38 months
Number of Subjects Treated With Sofosbuvir-based DAA Therapy Who Had Alanine Aminotransferase (ALT) Normalization Post Treatment (Normal Reference Range: 7 - 55 IU/L)
Change in ALT after sofosbuvir based DAA therapy
Measured: Median months from baseline to last ALT measurement is 41 months

Timeline

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

Aug 201631 Dec 2019

First posted27 Aug 2015 (estimated)
Study startAug 2016
Primary completion31 Dec 2019
Study completion31 Dec 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for HIVStudies of the same condition, open and under way.
More trials run by University of California, San FranciscoThe 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 4
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 68 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02533934
Sponsor's protocol ID: 12044
Other IDs: 1U01AI115714
Acronym: STOP-CO
Status last verified: Jan 2021
First submitted: 25 Aug 2015
Last updated: 2 Feb 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 2 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Retrospective/Prospective Cohort Study to Assess Safety, Tolerability, and Efficacy of Sofosbuvir Based Direct Acting Antiviral (DAA) Therapy for Hepatitis C Treatment in HIV/HCV Coinfected Subjects Pre or Post Liver Transplant
ClinicalTrials.gov ID: NCT02533934
Acronym / sponsor ID: STOP-CO / 12044
Conditions: HIV, Hepatitis C, Cirrhosis
Keywords: HIV, Hepatitis C, Liver Disease, HCV Treatment, transplant
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 68 participants (actual)
Lead sponsor: University of California, San FranciscoUniversity, hospital or other
Collaborators: National Institute of Allergy and Infectious Diseases (NIAID), Icahn School of Medicine at Mount Sinai, Columbia University, University of Pennsylvania, University of Maryland, College Park, Georgetown University, Johns Hopkins University, National Institutes of Health Clinical Center (CC)
Study start: Aug 2016 (actual)
Primary completion: 31 Dec 2019 (actual)
Study completion: 31 Dec 2019 (actual)
First posted: 27 Aug 2015 (estimated)
Results: Posted 2 Feb 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Retrospective/Prospective, open-label study using sofosbuvir based DAA therapy to treat HIV/HCV coinfected pre or post liver transplant participants

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Treatment with Sofosbuvir based HCV Therapy	Experimental	Drug: HarvoniProspective and retrospective treatment for HCV

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (24 listed)

Over 18 years of age at screening
Female participants of child bearing potential must have a negative urine pregnancy test at day 0 prior to dosing.
Has received a liver transplant for HCV or has decompensated cirrhosis (Child's Pugh score of 7 or greater)
Have HIV-1 infection and either:
Chronic HCV infection as documented by at least one measurement of plasma HCV RNA >= 1,000 IU/mL during screening and at least one of the following:

Key exclusion criteria (21 listed)

Positive HBsAg at screening.
History of any other clinically active chronic liver disease (e.g., hemochromatosis, autoimmune hepatitis, Wilson's disease, >=1 antitrypsin deficiency, alcoholic liver disease, and toxin exposures).
Treatment with unlicensed herbal/natural remedies suggested to be taken for hepatitis treatment, such as Milk thistle, St. Johns Wort or Cats Claw, within 28 days of start of treatment
Treatment with IFN, RBV, telaprevir or boceprevir or any other approved or experimental medication with known anti-HCV activity within 1 month prior to screening date
Any prior exposure to an HCV NS5a specific inhibitor

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
HarvoniAlso: SOF/LDVTreatment of Hepatitis C with sofosbuvir based HCC therapy	Drug	Treatment with Sofosbuvir based HCV Therapy

Primary outcome

Number of Participants With Sustained Virologic Response (SVR)
Time frame: Median time from end of treatment was 38.5 months
Sustained virologic response (SVR) defined by hepatitis C virus (HCV) RNA less than the lower level limit of quantification (LLOQ) of <15 IU/ml at a median time of 38.5 months after the end of sofosbuvir-based direct-acting antiviral (DAA) therapy

4 secondary outcomes

Reversal in Decompensation
Time frame: Median months from baseline to last MELD measurement is 48 months
Change in Liver Fibrosis
Time frame: Median months from baseline to last APRI measurement is 41 months Median months from baseline to last FIB-4 measurement is 41 months
HIV Viral Breakthrough or Relapse
Time frame: Median months from baseline to last HIV follow-up is 38 months
Number of Subjects Treated With Sofosbuvir-based DAA Therapy Who Had Alanine Aminotransferase (ALT) Normalization Post Treatment (Normal Reference Range: 7 - 55 IU/L)
Time frame: Median months from baseline to last ALT measurement is 41 months

Results and safety

Results posted to the registry on 2 Feb 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Adults With HIV and Chronic HCV and End-stage Liver Disease (ESLD) Pre-liver Transplant	42	42
Adults With HIV With Chronic HCV and Any Stage of Liver Disease Post-liver Transplant	26	26

Primary outcome: Number of Participants With Sustained Virologic Response (SVR)

Time frame: Median time from end of treatment was 38.5 months. Count of participants. Unit: Participants

Measure	Adults With HIV and Chronic HCV and End-stage Liver Disease (ESLD) Pre-liver Transplant n = 42	Adults With HIV With Chronic HCV and Any Stage of Liver Disease Post-liver Transplant n = 26
Value	38	25

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Prospective Subjects: from participants first dose until 6 months post treatment discontinuation, through study completion, up to twelve months, plus deaths at any-time. Retrospective Subjects: from participants first dose to end of treatment, through study completion, up to six months, plus deaths at any-time.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Adults With HIV and Chronic HCV and End-stage Liver Disease (ESLD) Pre-liver Transplant	18 of 42 (42.9%)	2 of 42 (4.8%)	10 of 42
Adults With HIV With Chronic HCV and Any Stage of Liver Disease Post-liver Transplant	7 of 26 (26.9%)	4 of 26 (15.4%)	3 of 26

Limitations and caveats (from the sponsor): This study was limited by the necessity to change the design from a prospective to a retrospective/prospective analysis. This change in study design resulted from the urgency in treating the HIV/HCV coinfected liver transplant candidate with DAAs, based on the dismal survival outcome in this cohort. By the time this trial was approved, many of the DAAs for HCV were approved, and centers immediately treated their decompensated HIV/HCV recipients.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 2 Feb 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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.

Peter Stock, MD, PhD principal investigator

University of California, San Francisco

Henry Masur, MD principal investigator

National Institutes of Health Clinical Center (CC)

8 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Harvoni in people with HIV and Hepatitis C, run by University of California, San Francisco at 8 sites in United States.

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 24 inclusion and 21 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 2 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Feb 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Participants With Sustained Virologic Response (SVR) (time frame: Median time from end of treatment was 38.5 months). 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 NCT02533934.

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 2 Feb 2021.