Hepatitis C, HIV, HIV/HCV Co-infection, Liver Fibrosis
Conditions
Keywords
Liver Fibrosis, Fibrosis, HIV, HCV, GS-6624, Hepatitis, Hepatitis C
Brief summary
The primary objective of this study is to assess the safety and tolerability of simtuzumab (formerly GS-6624) in HIV and/or hepatitis C virus (HCV)-infected adults with evidence of liver fibrosis.
Interventions
BIOLOGICALSimtuzumab
700 mg intravenously for a total of 12 infusions.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Gilead Sciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * HIV-infected individuals must have positive serologies with viral load suppressed below 400 copies/mL * HCV-infected individuals must have: * Chronic HCV infection with HCV RNA ≥ 2000 IU/ml AND at least 1 of the following: * Been null responder to previous pegylated interferon and ribavirin therapy OR * Failed to achieve sustained virologic response (SVR) on a regimen containing a direct-acting antiviral (DAA) in addition to pegylated interferon and ribavirin OR * Are unwilling to receive or have contraindications to interferon therapy for HCV * HIV/HCV co-infected individuals must have: * Positive HIV serologies with viral load suppressed below 400 copies/mL * Chronic HCV infection with HCV RNA ≥ 2000 IU/ml AND at least 1 of the following: * Been null responder to previous pegylated interferon and ribavirin therapy OR * Failed to achieve SVR on a regimen containing a direct-acting antiviral (DAA) in addition to pegylated interferon and ribavirin OR * Are unwilling to receive or have contraindications to interferon therapy for HCV * Willing to allow blood and tissue samples to be stored for future use to study HIV infection, immune function, liver disease and additional mechanisms involved in liver fibrosis among patients with HIV and/or HCV, which may not be related directly to the specific objectives of this study protocol * Have a primary care physician Key
Exclusion criteria
* Cause of liver fibrosis other than HCV or long-term antiretroviral therapy (ART) treatment for HIV * Currently being treated for HCV * Evidence of active Hepatitis A, B or D infections * History or evidence of hepatocellular carcinoma * Unwillingness to undergo a liver biopsy pre-treatment and post-treatment, or to undergo all other protocol required tests/procedures or return to the site for required visits * Presence of contraindications to magnetic resonance imaging (e.g., presence of any metal in the body, cardiac or neural pacemaker, aneurysm clip, cochlear implant, claustrophobia)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants Experiencing Treatment-Emergent Adverse Events | First dose date up to Week 24 plus 30 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Change From Baseline in Ishak Fibrosis Stage Score at Week 24 | Baseline; Week 24 | The Ishak fibrosis score measures the degree of liver fibrosis (scarring) and ranges from 0 (best) to 6 (worst). A negative value in change from baseline indicates an improvement and a positive value indicates worsening. |
| Change From Baseline in HVPG at Week 24 | Baseline; Week 24 | — |
| Change From Baseline in MQC at Week 24 | Baseline; Week 24 | — |
| Change From Baseline in Alpha SMA at Week 24 | Baseline; Week 24 | — |
| Change From Baseline in Liver Fibrosis as Estimated by MRE at Week 24 | Baseline; Week 24 | — |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at 1 study site in the United States. The first participant was screened on 04 October 2012. The last study visit occurred on 17 October 2014.
Pre-assignment details
37 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Simtuzumab in HIV Participants Participants with HIV received simtuzumab 700 mg intravenously every 2 weeks over a period of 24 weeks while continuing on standard therapy for HIV. | 4 |
| Simtuzumab in HCV Participants Participants with HCV received simtuzumab 700 mg intravenously every 2 weeks over a period of 24 weeks. | 6 |
| Simtuzumab in HIV/HCV Co-Infected Participants Participants co-infected with HIV and HCV received simtuzumab 700 mg intravenously every 2 weeks over a period of 24 weeks while continuing on standard therapy for HIV. | 8 |
| Total | 18 |
Baseline characteristics
| Characteristic | Simtuzumab in HIV Participants | Simtuzumab in HCV Participants | Simtuzumab in HIV/HCV Co-Infected Participants | Total |
|---|---|---|---|---|
| Age, Continuous | 56 years STANDARD_DEVIATION 6.3 | 58 years STANDARD_DEVIATION 5 | 54 years STANDARD_DEVIATION 5.6 | 56 years STANDARD_DEVIATION 5.6 |
| Alpha Smooth Muscle Actin (alpha SMA) | 6.59 percentage of alpha-SMA STANDARD_DEVIATION 4.351 | 12.58 percentage of alpha-SMA STANDARD_DEVIATION 12.184 | 13.32 percentage of alpha-SMA STANDARD_DEVIATION 15.803 | 11.58 percentage of alpha-SMA STANDARD_DEVIATION 12.549 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 6 Participants | 7 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Hepatic Venous Pressure Gradient (HVPG) | 8 millimeters of Mercury (mm Hg) STANDARD_DEVIATION 5.3 | 9 millimeters of Mercury (mm Hg) STANDARD_DEVIATION 3.7 | 8 millimeters of Mercury (mm Hg) STANDARD_DEVIATION 3.7 | 8 millimeters of Mercury (mm Hg) STANDARD_DEVIATION 3.8 |
| Ishak Fibrosis Score Stage 0 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ishak Fibrosis Score Stage 1 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ishak Fibrosis Score Stage 2 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ishak Fibrosis Score Stage 3 | 1 Participants | 1 Participants | 4 Participants | 6 Participants |
| Ishak Fibrosis Score Stage 4 | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Ishak Fibrosis Score Stage 5 | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Ishak Fibrosis Score Stage 6 | 2 Participants | 4 Participants | 2 Participants | 8 Participants |
| Magnetic Resonance Elastography (MRE) | 2.19 kPa STANDARD_DEVIATION 0.37 | 2.01 kPa STANDARD_DEVIATION 0.322 | 2.32 kPa STANDARD_DEVIATION 0.487 | 2.20 kPa STANDARD_DEVIATION 0.399 |
| Morphometric Quantitative Collagen (MQC) | 4.24 percentage of MQC STANDARD_DEVIATION 2.414 | 11.79 percentage of MQC STANDARD_DEVIATION 9.582 | 12.75 percentage of MQC STANDARD_DEVIATION 14.596 | 10.54 percentage of MQC STANDARD_DEVIATION 11.312 |
| Race/Ethnicity, Customized American Indian or Alaska native | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 2 Participants | 4 Participants | 6 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 2 Participants | 4 Participants | 2 Participants | 8 Participants |
| Sex: Female, Male Female | 0 Participants | 3 Participants | 1 Participants | 4 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 7 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 6 | 0 / 8 |
| other Total, other adverse events | 4 / 4 | 6 / 6 | 8 / 8 |
| serious Total, serious adverse events | 0 / 4 | 0 / 6 | 1 / 8 |
Outcome results
Primary
Percentage of Participants Experiencing Treatment-Emergent Adverse Events
Time frame: First dose date up to Week 24 plus 30 days
Population: The Safety Analysis Set included participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Simtuzumab in HIV Participants | Percentage of Participants Experiencing Treatment-Emergent Adverse Events | 100 percentage of participants |
| Simtuzumab in HCV Participants | Percentage of Participants Experiencing Treatment-Emergent Adverse Events | 100 percentage of participants |
| Simtuzumab in HIV/HCV Co-Infected Participants | Percentage of Participants Experiencing Treatment-Emergent Adverse Events | 100 percentage of participants |
Secondary
Change From Baseline in Alpha SMA at Week 24
Time frame: Baseline; Week 24
Population: Participants in the Full Analysis Set with liver biopsy area ≥ 4 mm\^2 (adequate for morphometry measurements) were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Simtuzumab in HIV Participants | Change From Baseline in Alpha SMA at Week 24 | 4.69 percentage of alpha-SMA | Standard Deviation 3.938 |
| Simtuzumab in HCV Participants | Change From Baseline in Alpha SMA at Week 24 | 5.27 percentage of alpha-SMA | Standard Deviation 6.973 |
| Simtuzumab in HIV/HCV Co-Infected Participants | Change From Baseline in Alpha SMA at Week 24 | 4.50 percentage of alpha-SMA | Standard Deviation 7.669 |
Secondary
Change From Baseline in HVPG at Week 24
Time frame: Baseline; Week 24
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Simtuzumab in HIV Participants | Change From Baseline in HVPG at Week 24 | 2 mm Hg | Standard Deviation 2.4 |
| Simtuzumab in HCV Participants | Change From Baseline in HVPG at Week 24 | 0 mm Hg | Standard Deviation 3.4 |
| Simtuzumab in HIV/HCV Co-Infected Participants | Change From Baseline in HVPG at Week 24 | 0 mm Hg | Standard Deviation 1.1 |
Secondary
Change From Baseline in Liver Fibrosis as Estimated by MRE at Week 24
Time frame: Baseline; Week 24
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Simtuzumab in HIV Participants | Change From Baseline in Liver Fibrosis as Estimated by MRE at Week 24 | 0.17 kPa | Standard Deviation 0.141 |
| Simtuzumab in HCV Participants | Change From Baseline in Liver Fibrosis as Estimated by MRE at Week 24 | 0.09 kPa | Standard Deviation 0.203 |
| Simtuzumab in HIV/HCV Co-Infected Participants | Change From Baseline in Liver Fibrosis as Estimated by MRE at Week 24 | 0.09 kPa | Standard Deviation 0.085 |
Secondary
Change From Baseline in MQC at Week 24
Time frame: Baseline; Week 24
Population: Participants in the Full Analysis Set with liver biopsy area ≥ 4 mm\^2 (adequate for morphometry measurements) were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Simtuzumab in HIV Participants | Change From Baseline in MQC at Week 24 | 2.07 percentage of MQC | Standard Deviation 5.333 |
| Simtuzumab in HCV Participants | Change From Baseline in MQC at Week 24 | -2.54 percentage of MQC | Standard Deviation 11.51 |
| Simtuzumab in HIV/HCV Co-Infected Participants | Change From Baseline in MQC at Week 24 | 1.27 percentage of MQC | Standard Deviation 9.612 |
Secondary
Number of Participants With a Change From Baseline in Ishak Fibrosis Stage Score at Week 24
The Ishak fibrosis score measures the degree of liver fibrosis (scarring) and ranges from 0 (best) to 6 (worst). A negative value in change from baseline indicates an improvement and a positive value indicates worsening.
Time frame: Baseline; Week 24
Population: Participants in the Full Analysis Set (who were enrolled into the study and received at least 1 dose of study drug) with available data were analyzed.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Simtuzumab in HIV Participants | Number of Participants With a Change From Baseline in Ishak Fibrosis Stage Score at Week 24 | Fibrosis worsened: 1 | 0 Participants |
| Simtuzumab in HIV Participants | Number of Participants With a Change From Baseline in Ishak Fibrosis Stage Score at Week 24 | Fibrosis did not change: 0 | 2 Participants |
| Simtuzumab in HIV Participants | Number of Participants With a Change From Baseline in Ishak Fibrosis Stage Score at Week 24 | Fibrosis improved: -2 | 0 Participants |
| Simtuzumab in HIV Participants | Number of Participants With a Change From Baseline in Ishak Fibrosis Stage Score at Week 24 | Fibrosis improved: -1 | 1 Participants |
| Simtuzumab in HIV Participants | Number of Participants With a Change From Baseline in Ishak Fibrosis Stage Score at Week 24 | Fibrosis worsened: 2 | 0 Participants |
| Simtuzumab in HCV Participants | Number of Participants With a Change From Baseline in Ishak Fibrosis Stage Score at Week 24 | Fibrosis did not change: 0 | 4 Participants |
| Simtuzumab in HCV Participants | Number of Participants With a Change From Baseline in Ishak Fibrosis Stage Score at Week 24 | Fibrosis improved: -2 | 1 Participants |
| Simtuzumab in HCV Participants | Number of Participants With a Change From Baseline in Ishak Fibrosis Stage Score at Week 24 | Fibrosis improved: -1 | 1 Participants |
| Simtuzumab in HCV Participants | Number of Participants With a Change From Baseline in Ishak Fibrosis Stage Score at Week 24 | Fibrosis worsened: 1 | 0 Participants |
| Simtuzumab in HCV Participants | Number of Participants With a Change From Baseline in Ishak Fibrosis Stage Score at Week 24 | Fibrosis worsened: 2 | 0 Participants |
| Simtuzumab in HIV/HCV Co-Infected Participants | Number of Participants With a Change From Baseline in Ishak Fibrosis Stage Score at Week 24 | Fibrosis worsened: 2 | 1 Participants |
| Simtuzumab in HIV/HCV Co-Infected Participants | Number of Participants With a Change From Baseline in Ishak Fibrosis Stage Score at Week 24 | Fibrosis worsened: 1 | 2 Participants |
| Simtuzumab in HIV/HCV Co-Infected Participants | Number of Participants With a Change From Baseline in Ishak Fibrosis Stage Score at Week 24 | Fibrosis improved: -2 | 0 Participants |
| Simtuzumab in HIV/HCV Co-Infected Participants | Number of Participants With a Change From Baseline in Ishak Fibrosis Stage Score at Week 24 | Fibrosis did not change: 0 | 5 Participants |
| Simtuzumab in HIV/HCV Co-Infected Participants | Number of Participants With a Change From Baseline in Ishak Fibrosis Stage Score at Week 24 | Fibrosis improved: -1 | 0 Participants |