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

NCT01707472 | Completed Phase 2 Results FDA Drug

• 1 other identifier: GS-US-321-0107
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Experiencing Treatment-Emergent Adverse Events

  First dose date up to Week 24 plus 30 days

Secondary Outcomes (5)

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

  Baseline; Week 24

• 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

Study Arms (3)

Simtuzumab in HIV Patients

EXPERIMENTAL

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

Biological: Simtuzumab

Simtuzumab in HCV Patients

EXPERIMENTAL

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

Biological: Simtuzumab

Simtuzumab in HIV/HCV Co-Infected Patients

EXPERIMENTAL

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

Biological: Simtuzumab

Interventions

Simtuzumab BIOLOGICAL

700 mg intravenously for a total of 12 infusions.

Also known as: Anti-LOXL2 Monoclonal Antibody, GS-6624

Simtuzumab in HCV Patients; Simtuzumab in HIV Patients; Simtuzumab in HIV/HCV Co-Infected Patients

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Gilead Sciences: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

NIH Department of Laboratory Medicine

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• 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.

  BACKGROUND

• 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.

  BACKGROUND

• 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.

  PMID: 28480218 DERIVED

• 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.

  PMID: 27232579 DERIVED

MeSH Terms

Conditions

Liver Cirrhosis; Hepatitis C; Fibrosis; Hepatitis

Interventions

simtuzumab

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2012
• First Posted: October 16, 2012
• Study Start: October 4, 2012
• Primary Completion: October 17, 2014
• Study Completion: October 17, 2014
• Last Updated: November 5, 2019
• Results First Posted: October 9, 2019

Record last verified: 2019-10

Locations

US (1)