Clinical trial NCT01707472: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Liver Fibrosis
Hepatitis C
HIV
HIV/HCV Co-infection
Keywords: Liver Fibrosis
Fibrosis
HIV
HCV
GS-6624
Hepatitis
Hepatitis C
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2012-10-16
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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)

Primary outcomes:
measure: Percentage of Participants Experiencing Treatment-Emergent Adverse Events
timeFrame: First dose date up to Week 24 plus 30 days
Secondary outcomes:
measure: Number of Participants With a Change From Baseline in Ishak Fibrosis Stage Score at Week 24
timeFrame: Baseline; Week 24
measure: Change From Baseline in HVPG at Week 24
timeFrame: Baseline; Week 24
measure: Change From Baseline in MQC at Week 24
timeFrame: Baseline; Week 24
measure: Change From Baseline in Alpha SMA at Week 24
timeFrame: Baseline; Week 24
measure: Change From Baseline in Liver Fibrosis as Estimated by MRE at Week 24
timeFrame: Baseline; Week 24
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: NIH Department of Laboratory Medicine
state: Maryland
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
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.
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.
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.
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.