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Study of Simtuzumab in HIV and/or Hepatitis C- Infected Adults With Liver Fibrosis

Primary Purpose

Liver Fibrosis, Hepatitis C, HIV

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Simtuzumab

About this trial

This is an interventional treatment trial for Liver Fibrosis focused on measuring Liver Fibrosis, Fibrosis, HIV, HCV, GS-6624, Hepatitis, Hepatitis C

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

NIH Department of Laboratory Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Simtuzumab in HIV Patients

Simtuzumab in HCV Patients

Simtuzumab in HIV/HCV Co-Infected Patients

Arm Description

HIV-infected participants will receive simtuzumab every 2 weeks for 24 weeks while continuing on standard therapy for HIV.

HCV-infected participants will receive simtuzumab every 2 weeks for 24 weeks.

HIV/HCV co-infected participants will receive simtuzumab every 2 weeks for 24 weeks while continuing on standard therapy for HIV.

Outcomes

Primary Outcome Measures

Percentage of Participants Experiencing Treatment-Emergent Adverse Events

Secondary Outcome Measures

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.

Change From Baseline in HVPG at Week 24

Change From Baseline in MQC at Week 24

Change From Baseline in Alpha SMA at Week 24

Change From Baseline in Liver Fibrosis as Estimated by MRE at Week 24

Full Information

NCT ID

NCT01707472

First Posted

September 11, 2012

Last Updated

October 22, 2019

Sponsor

Gilead Sciences

Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

1. Study Identification

Unique Protocol Identification Number

NCT01707472

Brief Title

Study of Simtuzumab in HIV and/or Hepatitis C- Infected Adults With Liver Fibrosis

Official Title

A Phase 2a Study of an Anti-LOXL2 Monoclonal Antibody (GS-6624) in HIV and/or Hepatitis C- Infected Subjects With Liver Fibrosis

Study Type

Interventional

2. Study Status

Record Verification Date

October 2019

Overall Recruitment Status

Completed

Study Start Date

October 4, 2012 (Actual)

Primary Completion Date

October 17, 2014 (Actual)

Study Completion Date

October 17, 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Gilead Sciences

Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Liver Fibrosis, Hepatitis C, HIV, HIV/HCV Co-infection

Keywords

Liver Fibrosis, Fibrosis, HIV, HCV, GS-6624, Hepatitis, Hepatitis C

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

18 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Simtuzumab in HIV Patients

Arm Type

Experimental

Arm Description

HIV-infected participants will receive simtuzumab every 2 weeks for 24 weeks while continuing on standard therapy for HIV.

Arm Title

Simtuzumab in HCV Patients

Arm Type

Experimental

Arm Description

HCV-infected participants will receive simtuzumab every 2 weeks for 24 weeks.

Arm Title

Simtuzumab in HIV/HCV Co-Infected Patients

Arm Type

Experimental

Arm Description

HIV/HCV co-infected participants will receive simtuzumab every 2 weeks for 24 weeks while continuing on standard therapy for HIV.

Intervention Type

Biological

Intervention Name(s)

Simtuzumab

Other Intervention Name(s)

Anti-LOXL2 Monoclonal Antibody, GS-6624

Intervention Description

700 mg intravenously for a total of 12 infusions.

Primary Outcome Measure Information:

Title

Percentage of Participants Experiencing Treatment-Emergent Adverse Events

Time Frame

First dose date up to Week 24 plus 30 days

Secondary Outcome Measure Information:

Title

Number of Participants With a Change From Baseline in Ishak Fibrosis Stage Score at Week 24

Description

Time Frame

Baseline; Week 24

Title

Change From Baseline in HVPG at Week 24

Time Frame

Baseline; Week 24

Title

Change From Baseline in MQC at Week 24

Time Frame

Baseline; Week 24

Title

Change From Baseline in Alpha SMA at Week 24

Time Frame

Baseline; Week 24

Title

Change From Baseline in Liver Fibrosis as Estimated by MRE at Week 24

Time Frame

Baseline; Week 24

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Gilead Study Director

Organizational Affiliation

Gilead Sciences

Official's Role

Study Director

Facility Information:

Facility Name

NIH Department of Laboratory Medicine

City

Bethesda

State/Province

Maryland

ZIP/Postal Code

20892

Country

United States

12. IPD Sharing Statement

Citations:

Citation

Meissner EG, McLaughlin M, Matthews LA, Kanwar B, Bornstein JD, Kovacs JA, et al. Longitudinal hepatic and PBMC gene expression profiling of HIV and/or HCV-infected patients with advanced liver disease treated with simtuzumab, an anti-LOXL2 antibody [Abstract 448]. Hepatology AASLD Abstracts 2014;60 Number 4 (Suppl):421A.

Results Reference

background

Citation

Han MAT, Gharib AM, Zhao X, Sinkus R, Rizvi BS, Matthews L, et al. Noninvasive Measures of Severity in Chronic Liver Disease, Moving Beyond Fibrosis [Abstract Sa1006]. Digestive Disease Week; 2015 16-19 May; Washington, D.C.

Results Reference

background

PubMed Identifier

28480218

Citation

Gharib AM, Han MAT, Meissner EG, Kleiner DE, Zhao X, McLaughlin M, Matthews L, Rizvi B, Abd-Elmoniem KZ, Sinkus R, Levy E, Koh C, Myers RP, Subramanian GM, Kottilil S, Heller T, Kovacs JA, Morse CG. Magnetic Resonance Elastography Shear Wave Velocity Correlates with Liver Fibrosis and Hepatic Venous Pressure Gradient in Adults with Advanced Liver Disease. Biomed Res Int. 2017;2017:2067479. doi: 10.1155/2017/2067479. Epub 2017 Apr 5.

Results Reference

derived

PubMed Identifier

27232579

Citation

Meissner EG, McLaughlin M, Matthews L, Gharib AM, Wood BJ, Levy E, Sinkus R, Virtaneva K, Sturdevant D, Martens C, Porcella SF, Goodman ZD, Kanwar B, Myers RP, Subramanian M, Hadigan C, Masur H, Kleiner DE, Heller T, Kottilil S, Kovacs JA, Morse CG. Simtuzumab treatment of advanced liver fibrosis in HIV and HCV-infected adults: results of a 6-month open-label safety trial. Liver Int. 2016 Dec;36(12):1783-1792. doi: 10.1111/liv.13177. Epub 2016 Jul 6.

Results Reference

derived

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Study of Simtuzumab in HIV and/or Hepatitis C- Infected Adults With Liver Fibrosis

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