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| ID | Type | Description | Link |
|---|---|---|---|
| 2025-523675-39 | Other Identifier | EU CT Number |
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The purpose of this study is to assess the safety and efficacy of efimosfermin alfa in the resolution of steatohepatitis and improvement of liver-related clinical outcome compared to placebo in individuals with MASH and biopsy-confirmed F2- or F3-stage fibrosis.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Participants receiving dose level 1 of efimosfermin alfa | Experimental |
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| Participants receiving dose level 2 of efimosfermin alfa | Experimental |
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| Participants receiving Placebo | Placebo Comparator |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Efimosfermin alfa | Drug | Efimosfermin alfa will be administered |
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| Measure | Description | Time Frame |
|---|---|---|
| Proportion of participants experiencing improvement in fibrosis by >=1 stage and no worsening of steatohepatitis at Week 52 | Proportion of participants experiencing improvement in fibrosis of greater than or equal to (>=) 1 stage by MASH clinical research network (CRN) fibrosis scores and no worsening of steatohepatitis (defined as no increase in nonalcoholic fatty liver disease activity score [NAS] for ballooning, inflammation, or steatosis) at 52 weeks will be assessed. MASH CRN fibrosis score ranges from 0 to 4, higher score indicates greater severity. NAS score ranges from 0 to 8, higher score indicates worse disease activity. | At Week 52 |
| Proportion of participants experiencing resolution of steatohepatitis reading and no worsening of MASH CRN fibrosis score at Week 52 | Resolution of steatohepatitis is defined as absence of fatty liver disease or isolated or simple steatosis without steatohepatitis and a NAS of 0 or 1 for inflammation, 0 for ballooning, and any value for steatosis. NAS score ranges from 0 to 8, higher score indicates worse disease activity. MASH CRN fibrosis score ranges from 0 to 4, higher score indicates greater severity. | At Week 52 |
| Time from randomization to an adjudicated composite liver-related clinical outcome | Liver-related outcome will comprised of all-cause mortality; transplantation; occurrence of significant hepatic events. | From Randomization (Day 1) to 48 months |
| Measure | Description | Time Frame |
|---|---|---|
| Number of participants with treatment-emergent adverse events (TEAEs) and TEAEs by severity | At Week 52 and at Month 48 | |
| Number of participants with TEAEs leading to discontinuation and TEAEs leading to discontinuation by severity | At Week 52 and at Month 48 |
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Inclusion Criteria:
Exclusion Criteria:
Contraindication or ineligibility for percutaneous liver biopsy
ALT or AST >=5 x upper limit of normal (ULN)
Total bilirubin >=1.3 milligram per deciliter (mg/dL). Individuals with documented Gilbert's syndrome may be enrolled if they experienced an isolated increase in total bilirubin of >=1.3 mg/dL and direct bilirubin is <=20% of total bilirubin; otherwise, the individual will be excluded.
Serum albumin <=3.5 grams per deciliter (g/dL)
International normalized ratio (INR) >=1.3 not due to therapeutic anticoagulation. Individuals receiving chronic anticoagulant treatment with higher INR values may be enrolled at the discretion of the Investigator and Study Medical Monitor.
Alkaline phosphatase (ALP) >=2*ULN
Platelet (PLT) count <140,000 per (/) cubic millimeter (mm^3); individuals with a PLT count between 110,000/mm^3 and 140,000/mm^3 may be enrolled after discussion with the Study Medical Monitor.
Serum creatinine >=1.5 mg/dL or creatinine clearance <=60 milliliter (mL)/minute (min)/1.73 square meter by Chronic Kidney Disease Epidemiology Collaboration equation
Alpha-fetoprotein >=20 nanogram per milliliter (ng/mL)
Glycated hemoglobin >=9.0%
Model for End-Stage Liver Disease score >=12 unless the score is elevated in the absence of liver dysfunction (e.g., Gilbert's syndrome)
Phosphatidyl ethanol (PEth) >=80 ng/mL at Screening
Evidence of infection with any of the following:
Chronic liver disease from any other cause including, but not limited to, alcoholic liver disease; evidence of portal hypertension; viral hepatitis or any history or evidence of cirrhosis on screening liver biopsy; or decompensated liver disease such as clinical ascites, bleeding gastroesophageal varices, hepatorenal syndrome, or hepatic encephalopathy prior to Screening or Day 1.
Current or history of excessive alcohol intake for >=3 months within the 12-month period prior to Screening
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| US GSK Clinical Trials Call Center | Contact | 877-379-3718 | GSKClinicalSupportHD@gsk.com | |
| EU GSK Clinical Trials Call Center | Contact | +44 (0) 20 89904466 | GSKClinicalSupportHD@gsk.com |
| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Recruiting | Arcadia | California | 91006 | United States |
Study Sponsor will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/About\_GSK\_Patient\_Level\_Data\_Sharing\_Final\_13July2023.pdf
Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or asset(s) with development terminated across all indications.
Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months, but an extension may be granted, when justified, for up to 6 months.
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This is a double blind study.
| Efimosfermin alfa | Drug | Efimosfermin alfa will be administered |
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| Placebo | Drug | Placebo will be administered |
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| Number of participants with Grade 3 and Grade 4 laboratory abnormalities | At Week 52 and at Month 48 |
| Proportion of participants experiencing resolution of steatohepatitis on overall histopathological reading and improvement in liver fibrosis of >=1 stage at Week 52 | Resolution of steatohepatitis is defined as absence of fatty liver disease or isolated or simple steatosis without steatohepatitis on overall histopathological reading on liver biopsies. Proportion of participants experiencing improvement in fibrosis of >=1 stage by MASH CRN fibrosis scores and resolution of steatohepatitis on overall histopathological reading at 52 weeks will be assessed. MASH CRN fibrosis score ranges from 0 to 4, higher score indicates greater severity | At Week 52 |
| Proportion of participants experiencing improvement in fibrosis by >=1 stage and no worsening of Steatohepatitis at Month 48 | Proportion of participants experiencing improvement in fibrosis of >=1 stage by MASH CRN fibrosis scores and no worsening of steatohepatitis (defined as no increase in NAS for ballooning, inflammation, or steatosis) at Month 48 will be assessed. MASH CRN fibrosis score ranges from 0 to 4, higher score indicates greater severity. NAS score ranges from 0 to 8, higher score indicates worse disease activity. | At Month 48 |
| Proportion of participants experiencing improvement in fibrosis by >=2 stage and no worsening of Steatohepatitis at Week 52 and Month 48 | Proportion of participants experiencing improvement in fibrosis of >=2 stage by MASH CRN fibrosis scores and no worsening of steatohepatitis (defined as no increase in NAS for ballooning, inflammation, or steatosis) at at Week 52 and Month 48 will be assessed. MASH CRN fibrosis score ranges from 0 to 4, higher score indicates greater severity. NAS score ranges from 0 to 8, higher score indicates worse disease activity | At Week 52 and Month 48 |
| Proportion of participants experiencing resolution of steatohepatitis reading and no worsening of MASH CRN score at Month 48 | Resolution of steatohepatitis is defined as absence of fatty liver disease or isolated or simple steatosis without steatohepatitis and a NAS of 0 or 1 for inflammation, 0 for ballooning, and any value for steatosis. NAS score ranges from 0 to 8, higher score indicates worse disease activity. MASH CRN fibrosis score ranges from 0 to 4, higher score indicates greater severity. | At Month 48 |
| Absolute change from Baseline in vibration-controlled transient elastography-liver stiffness measurement (VCTE-LSM) | Baseline (Day 1), Week 52 and Month 48 |
| Percent change from Baseline in VCTE-LSM | Baseline (Day 1), Week 52 and Month 48 |
| Absolute change from Baseline in controlled attenuation parameter (CAP) scores | The CAP score is measured by FibroScan, will be used to quantify and detect liver fat. CAP less than (<) 238 decibel-milliwatts (dB/m) indicated no hepatic steatosis, 238 less than or equal to (<=) CAP <=259 dB/m denoted mild steatosis, 260 <=CAP <=291 dB/m indicated moderate steatosis, and CAP greater than (>) 291 dB/m denoted severe steatosis. | Baseline (Day 1), Week 52 and Month 48 |
| Percent change from Baseline in CAP scores | The CAP score is measured by FibroScan, will be used to quantify and detect liver fat. CAP <238 dB/m indicated no hepatic steatosis, 238 <=CAP <=259 dB/m denoted mild steatosis, 260 <=CAP <=291 dB/m indicated moderate steatosis, and CAP >291 dB/m denoted severe steatosis. | Baseline (Day 1), Week 52 and Month 48 |
| Proportion of participants achieving Change from Baseline in VCTE-LSM >=30 percent (%) at Week 52 and Month 48 | VCTE-LSM is a non-invasive test that uses vibration-controlled transient elastography to measure the stiffness of the liver in kilopascal (kPa). | Baseline (Day 1), Week 52 and Month 48 |
| Absolute change from Baseline in magnetic resonance elastography (MRE) scores | MRE is a non-invasive imaging technique that combine magnetic resonance imaging (MRI) scanning with low-frequency mechanical vibrations to measure the stiffness of liver. MRE scores <2.5 is normal, 2.5 - 3.0 Normal or inflammation, 3.0 - 3.5 Stage 1-2 fibrosis, 3.5 - 4.0 Stage 2-3 fibrosis, 4.0 - 5.0 Stage 3-4 fibrosis and > 5.0 Stage 4 fibrosis. | Baseline (Day 1), Week 52 and Month 48 |
| Percent change from Baseline in MRE Score | MRE is a non-invasive imaging technique that combine MRI scanning with low-frequency mechanical vibrations to measure the stiffness of liver. MRE scores <2.5 is normal, 2.5 - 3.0 Normal or inflammation, 3.0 - 3.5 Stage 1-2 fibrosis, 3.5 - 4.0 Stage 2-3 fibrosis, 4.0 - 5.0 Stage 3-4 fibrosis and > 5.0 Stage 4 fibrosis. | Baseline (Day 1), Week 52 and Month 48 |
| Absolute change from Baseline in Enhanced Liver Fibrosis (ELF) Score | The ELF score will be calculated using a published algorithm combining the values of a set of extracellular matrix markers. The ELF score is used as a prognostic marker for disease progression: ELF score <9.8: Low risk of progression, ELF score 9.8 to <11.3: Moderate risk of progression and ELF score >=11.3: High risk of progression. | Baseline (Day 1), Week 52 and Month 48 |
| Percent change from Baseline in ELF Score | The ELF score will be calculated using a published algorithm combining the values of a set of extracellular matrix markers. The ELF score is used as a prognostic marker for disease progression: ELF score <9.8: Low risk of progression, ELF score 9.8 to <11.3: Moderate risk of progression and ELF score >=11.3: High risk of progression. | Baseline (Day 1), Week 52 and Month 48 |
| Proportion of participants experiencing improvement in ELF score of >=0.5 | The ELF score will be calculated using a published algorithm combining the values of a set of extracellular matrix markers. The ELF score is used as a prognostic marker for disease progression: ELF score <9.8: Low risk of progression, ELF score 9.8 to <11.3: Moderate risk of progression and ELF score >=11.3: High risk of progression. | At Week 52 and Month 48 |
| Absolute change from Baseline in hepatic fat fraction (HFF) by MRI-derived proton density fat fraction (PDFF) | HFF is the percentage of fat in the liver measured by MRI proton density fat fraction technique, which ranges from 0-75%. Greater than 5% is considered extra fat in the liver. | Baseline (Day 1), Week 52 and Month 48 |
| Percent change from Baseline in HFF by MRI-PDFF | HFF is the percentage of fat in the liver measured by MRI proton density fat fraction technique, which ranges from 0-75%. Greater than 5% is considered extra fat in the liver. | Baseline (Day 1), Week 52 and Month 48 |
| Absolute change from Baseline in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (International units per liter) | Baseline (Day 1), Week 52 and Month 48 |
| Percent change from Baseline in ALT and AST (International units per liter) | Baseline (Day 1), Week 52 and Month 48 |
| Absolute change from Baseline in ALT and AST ratio (ALT/AST) | ALT/AST ratio is calculated as ALT/AST ratio equal to ALT divided by AST. | Baseline (Day 1), Week 52 and Month 48 |
| Percent change from Baseline in ALT and AST ratio (ALT/AST) | ALT/AST ratio is calculated as ALT/AST ratio equal to ALT divided by AST. | Baseline (Day 1), Week 52 and Month 48 |
| Proportion of participants experiencing ALT and HFF normalization at Week 52 and Month 48 | At Week 52 and Month 48 |
| Proportion of participants experiencing HFF <=5% at Week 52 and Month 48 | HFF is the percentage of fat in the liver measured by MRI proton density fat fraction technique, which ranges from 0-75%. Less than or equal to 5% is considered normal (no significant fatty infiltration (steatosis) in the liver. | At Week 52 and Month 48 |
| Change from Baseline in glycated hemoglobin (HbA1c) (Percentage of HbA1c) in participants with Type 2 Diabetes Mellitus (T2DM) | Baseline (Day 1), Week 52 and Month 48 |
| Change from Baseline in body weight (kilograms) | Baseline (Day 1), Week 52 and Month 48 |
| Change from Baseline in fasting total cholesterol, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)- cholesterol, and triglycerides (Millimoles per liter) | Baseline (Day 1), Week 52 and Month 48 |
| Proportion of participants with antidrug and antiFGF21 antibody (ADA) | At Week 52 and Month 48 |
| Change from Baseline in Chronic Liver Disease Questionnaire-Nonalcoholic Steatohepatitis (CLDQ-NASH) in domain and total score | CLDQ-NASH is a NASH-specific health-related quality of life (HRQoL) Patient-Reported Outcomes (PRO) designed to assess 6 health domains over 36 items: abdominal symptoms (3 items), activity/energy (5 items), emotional health (9 items), fatigue (6 items), systemic symptoms (6 items) and worry (7 items). The domain scores range from 1 to 7, higher scores indicating better HRQoL. A score of 1 meaning the symptom being assessed is "present always" while a score of 7 means the symptom is "never present". The total score can range from 36 to 252, a higher score corresponds to a better quality of life while a lower score corresponds to a worse quality of life. | Baseline (Day 1), Week 52 and Month 48 |
| Change from Baseline in Short Form-36 (SF-36) component and domain scores at Week 52 and Month 48 | SF-36 is a generic HRQoL PRO designed to assess 8 health domains over 36 items: physical functioning (10 items), bodily pain (2 items), role limitations due to physical problems (4 items), role limitations due to emotional problems (3 items), general health (5 items), mental health (5 items), social functioning (2 items), and vitality (4 items). Each domain is scored from 0 (poorer health) to 100 (better health). SF-36 is scored into 8 domains and 2 component scores: physical component summary (PCS) and mental component summary (MCS). The domain and component scores range from 0 to 100, with higher scores indicating better HRQoL. | Baseline (Day 1), Week 52 and Month 48 |
| Serum drug Concentration of efimosfermin alfa | Up to Month 48 |
| GSK Investigational Site | Recruiting | Covina | California | 91723 | United States |
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| GSK Investigational Site | Recruiting | Los Angeles | California | 90057 | United States |
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| GSK Investigational Site | Recruiting | Santa Maria | California | 93458 | United States |
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| GSK Investigational Site | Recruiting | Van Nuys | California | 91405 | United States |
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| GSK Investigational Site | Recruiting | Boynton Beach | Florida | 33435 | United States |
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| GSK Investigational Site | Recruiting | Cape Coral | Florida | 33914 | United States |
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| GSK Investigational Site | Recruiting | Hialeah | Florida | 33016 | United States |
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| GSK Investigational Site | Recruiting | Hialeah | Florida | 33016 | United States |
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| GSK Investigational Site | Recruiting | Inverness | Florida | 34452 | United States |
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| GSK Investigational Site | Recruiting | Jacksonville | Florida | 32216 | United States |
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| GSK Investigational Site | Recruiting | Kissimmee | Florida | 34744 | United States |
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| GSK Investigational Site | Recruiting | Lakeland | Florida | 33803 | United States |
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| GSK Investigational Site | Recruiting | Maitland | Florida | 32751 | United States |
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| GSK Investigational Site | Recruiting | Miami | Florida | 33135 | United States |
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| GSK Investigational Site | Recruiting | Miami | Florida | 33144 | United States |
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| GSK Investigational Site | Recruiting | Miami | Florida | 33155 | United States |
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| GSK Investigational Site | Recruiting | Miami | Florida | 33156 | United States |
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| GSK Investigational Site | Recruiting | Miami | Florida | 33184 | United States |
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| GSK Investigational Site | Recruiting | Miami Lakes | Florida | 33014 | United States |
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| GSK Investigational Site | Recruiting | Ocala | Florida | 34471 | United States |
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| GSK Investigational Site | Recruiting | Palmetto Bay | Florida | 33157 | United States |
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| GSK Investigational Site | Recruiting | Topeka | Kansas | 66606 | United States |
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| GSK Investigational Site | Recruiting | Springfield | Missouri | 62703 | United States |
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| GSK Investigational Site | Recruiting | St Louis | Missouri | 63141 | United States |
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| GSK Investigational Site | Recruiting | East Syracuse | New York | 13057 | United States |
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| GSK Investigational Site | Recruiting | New York | New York | 10036 | United States |
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| GSK Investigational Site | Recruiting | New York | New York | 10036 | United States |
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| GSK Investigational Site | Recruiting | Morehead City | North Carolina | 28557 | United States |
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| GSK Investigational Site | Recruiting | Akron | Ohio | 44320 | United States |
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| GSK Investigational Site | Recruiting | Springboro | Ohio | 45066 | United States |
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| GSK Investigational Site | Recruiting | Chattanooga | Tennessee | 37421 | United States |
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| GSK Investigational Site | Recruiting | Austin | Texas | 78704 | United States |
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| GSK Investigational Site | Recruiting | Austin | Texas | 78759 | United States |
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| GSK Investigational Site | Recruiting | Bellaire | Texas | 77401 | United States |
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| GSK Investigational Site | Recruiting | Brownsville | Texas | 78526 | United States |
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| GSK Investigational Site | Recruiting | Dallas | Texas | 75243 | United States |
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| GSK Investigational Site | Recruiting | DeSoto | Texas | 75115 | United States |
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| GSK Investigational Site | Recruiting | Richmond | Texas | 77406 | United States |
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| GSK Investigational Site | Recruiting | San Antonio | Texas | 78215 | United States |
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| GSK Investigational Site | Recruiting | San Antonio | Texas | 78229 | United States |
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| GSK Investigational Site | Recruiting | Seabrook | Texas | 77586 | United States |
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| GSK Investigational Site | Recruiting | Sugar Land | Texas | 77479 | United States |
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| GSK Investigational Site | Recruiting | Tomball | Texas | 77375 | United States |
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| GSK Investigational Site | Recruiting | Waco | Texas | 76710 | United States |
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| GSK Investigational Site | Recruiting | Waco | Texas | 76712 | United States |
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| GSK Investigational Site | Recruiting | West Jordan | Utah | 84088 | United States |
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| GSK Investigational Site | Recruiting | Manassas | Virginia | 20110 | United States |
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| GSK Investigational Site | Recruiting | Seattle | Washington | 98105 | United States |
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| ID | Term |
|---|---|
| D065626 | Non-alcoholic Fatty Liver Disease |
| ID | Term |
|---|---|
| D005234 | Fatty Liver |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
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