Pilot Study of Simtuzumab in the Treatment of Liver Fibrosis
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|ClinicalTrials.gov Identifier: NCT01452308|
Recruitment Status : Completed
First Posted : October 14, 2011
Last Update Posted : February 3, 2014
This study will evaluate the safety and tolerability of simtuzumab (GS-6624) in patients with fibrosis of the liver.
Up to 20 participants will be enrolled into two sequential cohorts. Cohort 1 will consist of 10 participants who will receive simtuzumab every other week for a total of 3 infusions. Participants in Cohort 2 (10 subjects) will also receive simtuzumab every other week for a total of 3 infusions; the dose will depend on the safety and tolerability of simtuzumab seen in Cohort 1.
Participants from both cohorts who have completed the main study will be allowed to continue on simtuzumab treatment for an additional extension period, and will receive up to 13 additional infusions of simtuzumab at a fixed dose of 700 mg for an additional 24 weeks.
|Condition or disease||Intervention/treatment||Phase|
|Liver Fibrosis||Biological: Simtuzumab||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||20 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2a, Pilot, Open-Label Trial Evaluating the Safety, Tolerability and Pharmacodynamic Effects of GS-6624 in Subjects With Fibrosis of the Liver|
|Study Start Date :||November 2011|
|Actual Primary Completion Date :||January 2013|
|Actual Study Completion Date :||August 2013|
Experimental: Cohort 1
Participants will receive simtuzumab at a dose of 10 mg/kg by intravenous (IV) infusion every other week for a total of 3 infusions.
Other Name: GS-6624
Experimental: Cohort 2
Participants will receive simtuzumab IV every other week for a total of 3 infusions. The dose will depend on the safety and tolerability of simtuzumab seen in Cohort 1 but will not exceed 20 mg/kg.
Other Name: GS-6624
- Incidence of adverse events on multiple, escalating IV doses of simtuzumab [ Time Frame: Through Week 14 ]The endpoints to be evaluated will include graded Adverse Events, laboratory abnormalities, and vital sign measurements
- Assessment of serum concentration of simtuzumab [ Time Frame: Through Week 14 ]Trough concentrations will be summarized by day, treatment and dose.
- Antibody formation to simtuzumab (anti-simtuzumab Abs) [ Time Frame: Through Week 14 ]Immunogenicity endpoints will be geometric mean titer (GMT) and geometric mean fold rate (GMFR) for a select set of antibodies.
- Measurement of pharmacodynamic (PD) markers after administration of simtuzumab [ Time Frame: Through Week 14 ]Pharmacodynamic markers include: Tissue PD markers through mRNA expression, LOXL2, LOX, Other LOXL proteins, αSMA, Collagen 1A1, NFKB1, Caspase 1, SMAD, and NOD; Serum and plasma PD markers include: APRI, LOXL2, Osteopontin, Hyaluronic Acid, CXCL 9, 10 and 11, MMP1, MMP3, MMP9, TIMP1, CD40L, TGF-β1, ET-1, VEGF, GAL3, IL-6 / IL-8 / TNFα / IFNγ, α2-macroglobulin, Apolipoprotein A1.
- Assessing the effects of chronic dosing of simtuzumab on liver structure and fibrotic markers [ Time Frame: Up to 24 weeks ]Measuring the effect of an additional 24 weeks of simtuzumab dosing on liver histology, LOXL2 and mRNA expression in the liver and serum markers of liver fibrosis
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01452308
|United States, New York|
|Weill Cornell Medical College: NewYork-Presbyterian Hospital|
|New York, New York, United States, 10065|
|Study Director:||Jeffrey Bornstein, MD||Gilead Sciences|