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| Name | Class |
|---|---|
| National Institute of Allergy and Infectious Diseases (NIAID) | NIH |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Simtuzumab in HIV Patients | Experimental | HIV-infected participants will receive simtuzumab every 2 weeks for 24 weeks while continuing on standard therapy for HIV. |
|
| Simtuzumab in HCV Patients | Experimental | HCV-infected participants will receive simtuzumab every 2 weeks for 24 weeks. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Simtuzumab | Biological | 700 mg intravenously for a total of 12 infusions. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Experiencing Treatment-Emergent Adverse Events | First dose date up to Week 24 plus 30 days |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline; Week 24 |
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Key Inclusion Criteria:
HIV-infected individuals must have positive serologies with viral load suppressed below 400 copies/mL
HCV-infected individuals must have:
HIV/HCV co-infected individuals must have:
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:
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| Name | Affiliation | Role |
|---|---|---|
| Gilead Study Director | Gilead Sciences | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| NIH Department of Laboratory Medicine | Bethesda | Maryland | 20892 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| Background | 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. | ||
| 28480218 | Derived | 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. |
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37 participants were screened.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Simtuzumab in HIV Participants | Participants with human immunodeficiency virus (HIV) received simtuzumab 700 mg intravenously every 2 weeks over a period of 24 weeks while continuing on standard therapy for HIV. |
| FG001 | Simtuzumab in HCV Participants | Participants with hepatitis C virus (HCV) received simtuzumab 700 mg intravenously every 2 weeks over a period of 24 weeks. |
| FG002 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
The Safety Analysis Set included participants who received at least one dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | Simtuzumab in HCV Participants |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Participants Experiencing Treatment-Emergent Adverse Events | The Safety Analysis Set included participants who received at least one dose of study drug. | Posted | Number | percentage of participants | First dose date up to Week 24 plus 30 days |
|
First dose date to Week 24 plus 30 Days
The Safety Analysis Set included participants who received at least one dose of study drug.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lymphocytosis | Blood and lymphatic system disorders | MedDRA 17.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Gilead Clinical Study Information Center | Gilead Sciences | 1-833-445-3230 (GILEAD-0) | GileadClinicalTrials@gilead.com |
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| ID | Term |
|---|---|
| D008103 | Liver Cirrhosis |
| D006526 | Hepatitis C |
| D005355 | Fibrosis |
| D006505 | Hepatitis |
| ID | Term |
|---|---|
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C000613471 | simtuzumab |
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|
| 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 |
| 27232579 | 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. |
Participants with HCV received simtuzumab 700 mg intravenously every 2 weeks over a period of 24 weeks.
| BG002 | 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. |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants | No |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants | No |
|
| Race/Ethnicity, Customized | Count of Participants | Participants | No |
|
| Ishak Fibrosis Score | The Ishak fibrosis score measures the degree of liver fibrosis (scarring) and ranges from 0 (best) to 6 (worst). | Count of Participants | Participants | No |
|
| Hepatic Venous Pressure Gradient (HVPG) | Mean | Standard Deviation | millimeters of Mercury (mm Hg) |
|
| Morphometric Quantitative Collagen (MQC) | Mean | Standard Deviation | percentage of MQC |
|
| Alpha Smooth Muscle Actin (alpha SMA) | Mean | Standard Deviation | percentage of alpha-SMA |
|
| Magnetic Resonance Elastography (MRE) | Liver fibrosis is measured by MRE in kilopascal (kPa) | Mean | Standard Deviation | kPa |
|
| OG002 |
| 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. |
|
|
| 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. | 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. | Posted | Count of Participants | Participants | No | Baseline; Week 24 |
|
|
|
| Secondary | Change From Baseline in HVPG at Week 24 | Participants in the Full Analysis Set were analyzed. | Posted | Mean | Standard Deviation | mm Hg | Baseline; Week 24 |
|
|
|
| Secondary | Change From Baseline in MQC at Week 24 | Participants in the Full Analysis Set with liver biopsy area ≥ 4 mm^2 (adequate for morphometry measurements) were analyzed. | Posted | Mean | Standard Deviation | percentage of MQC | Baseline; Week 24 |
|
|
|
| Secondary | Change From Baseline in Alpha SMA at Week 24 | Participants in the Full Analysis Set with liver biopsy area ≥ 4 mm^2 (adequate for morphometry measurements) were analyzed. | Posted | Mean | Standard Deviation | percentage of alpha-SMA | Baseline; Week 24 |
|
|
|
| Secondary | Change From Baseline in Liver Fibrosis as Estimated by MRE at Week 24 | Participants in the Full Analysis Set with available data were analyzed. | Posted | Mean | Standard Deviation | kPa | Baseline; Week 24 |
|
|
|
| 0 |
| 4 |
| 0 |
| 4 |
| 4 |
| 4 |
| EG001 | Simtuzumab in HCV Participants | Participants with HCV received simtuzumab 700 mg intravenously every 2 weeks over a period of 24 weeks. | 0 | 6 | 0 | 6 | 6 | 6 |
| EG002 | 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. | 0 | 8 | 1 | 8 | 8 | 8 |
| Vomiting | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 17.1 | Systematic Assessment |
|
| Bacteraemia | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
|
| Gallbladder injury | Injury, poisoning and procedural complications | MedDRA 17.1 | Systematic Assessment |
|
| Abdominal tenderness | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Aphthous stomatitis | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Glossitis | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 17.1 | Systematic Assessment |
|
| Infusion site rash | General disorders | MedDRA 17.1 | Systematic Assessment |
|
| Malaise | General disorders | MedDRA 17.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 17.1 | Systematic Assessment |
|
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA 17.1 | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
|
| Oral candidiasis | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA 17.1 | Systematic Assessment |
|
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 17.1 | Systematic Assessment |
|
| Procedural pain | Injury, poisoning and procedural complications | MedDRA 17.1 | Systematic Assessment |
|
| Activated partial thromboplastin time prolonged | Investigations | MedDRA 17.1 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 17.1 | Systematic Assessment |
|
| Amylase increased | Investigations | MedDRA 17.1 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 17.1 | Systematic Assessment |
|
| Bilirubin conjugated increased | Investigations | MedDRA 17.1 | Systematic Assessment |
|
| Blood albumin decreased | Investigations | MedDRA 17.1 | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA 17.1 | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | MedDRA 17.1 | Systematic Assessment |
|
| Blood creatine phosphokinase abnormal | Investigations | MedDRA 17.1 | Systematic Assessment |
|
| Blood creatinine decreased | Investigations | MedDRA 17.1 | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA 17.1 | Systematic Assessment |
|
| Blood lactate dehydrogenase abnormal | Investigations | MedDRA 17.1 | Systematic Assessment |
|
| Gamma-glutamyltransferase increased | Investigations | MedDRA 17.1 | Systematic Assessment |
|
| Haemoglobin decreased | Investigations | MedDRA 17.1 | Systematic Assessment |
|
| International normalised ratio increased | Investigations | MedDRA 17.1 | Systematic Assessment |
|
| Lipase increased | Investigations | MedDRA 17.1 | Systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA 17.1 | Systematic Assessment |
|
| White blood cells urine positive | Investigations | MedDRA 17.1 | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 17.1 | Systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 17.1 | Systematic Assessment |
|
| Hypernatraemia | Metabolism and nutrition disorders | MedDRA 17.1 | Systematic Assessment |
|
| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA 17.1 | Systematic Assessment |
|
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA 17.1 | Systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 17.1 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 17.1 | Systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 17.1 | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 17.1 | Systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 17.1 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Lower extremity mass | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Cognitive disorder | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
|
| Lethargy | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
|
| Migraine | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
|
| Bipolar disorder | Psychiatric disorders | MedDRA 17.1 | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA 17.1 | Systematic Assessment |
|
| Glycosuria | Renal and urinary disorders | MedDRA 17.1 | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA 17.1 | Systematic Assessment |
|
| Proteinuria | Renal and urinary disorders | MedDRA 17.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met:
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D006525 | Hepatitis, Viral, Human |
| D014777 | Virus Diseases |
| D018178 | Flaviviridae Infections |
| D012327 | RNA Virus Infections |
| Fibrosis did not change: 0 |
|
| Fibrosis worsened: 1 |
|
| Fibrosis worsened: 2 |
|