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Also known as GS-6624, Anti-LOXL2 Monoclonal Antibody, AB0024
Simtuzumab · 7 trials · 9 indications
The endpoints to be evaluated will include graded Adverse Events, laboratory abnormalities, and vital sign measurements
Progression free survival is measured as time from date of randomization to the earliest event time of death regardless of cause or first indication of disease progression.
Overall response for the study drug is defined by the reduction in bone marrow fibrosis score which is on a scale of 0-3 where 0 indicates the scattered linear reticulin with no fiber intersections representing normal marrow and 3 indicates dense increase in reticulin fibrosis with fiber intersections, often with osteosclerosis. Reduction from baseline of score indicates improvement in clinical condition.
To characterize the safety, tolerability, and pharmacokinetics (PK) of GS-6624 after multiple intravenous (IV) administrations in subjects with idiopathic pulmonary fibrosis (IPF).
| Arm | Type | Description |
|---|---|---|
| Treatment Arm A | EXPERIMENTAL | Simtuzumab 75 mg for 96 weeks |
| Treatment Arm B | EXPERIMENTAL | Simtuzumab 125 mg for 96 weeks |
| Treatment Arm C | PLACEBO_COMPARATOR | Placebo for 96 weeks |
| 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. |
| Cohort 1 | EXPERIMENTAL | Participants will receive simtuzumab at a dose of 10 mg/kg by intravenous (IV) infusion every other week for a total of 3 infusions. |
| Cohort 2 | EXPERIMENTAL | 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. |
| Simtuzumab (open-label) | EXPERIMENTAL | Participants will receive simtuzumab 700 mg plus gemcitabine in cycles of 28 days for up to 3 years. |
| Simtuzumab 200 mg (randomized) | EXPERIMENTAL | Participants will receive simtuzumab 200 mg plus gemcitabine in cycles of 28 days for up to 3 years. |
| Simtuzumab 700 mg (randomized) | EXPERIMENTAL | Participants will receive simtuzumab 700 mg plus gemcitabine in cycles of 28 days for up to 3 years. |
| Placebo (randomized) | PLACEBO_COMPARATOR | Participants will receive placebo to match simtuzumab plus gemcitabine in cycles of 28 days for up to 3 years. |
| Simtuzumab 200 mg | EXPERIMENTAL | Participants in Stage 1 of study will receive simtuzumab 200 mg for up to 24 weeks. Treatment could be continued if there is evidence of clinical benefit as judged by the treating physician. |
| Simtuzumab 700 mg | EXPERIMENTAL | Participants in Stage 1 of study will receive simtuzumab 700 mg for up to 24 weeks. Treatment could be continued if there is evidence of clinical benefit as judged by the treating physician. |
| Simtuzumab 200 mg+Ruxolitinib | EXPERIMENTAL | In Stage 2, participants on stable doses of ruxolitinib will receive simtuzumab 200 mg for at least 24 weeks. Treatment could be continued if there is evidence of clinical benefit as judged by the treating physician. |
| Simtuzumab 700 mg+Ruxolitinib | EXPERIMENTAL | In Stage 2, participants on stable doses of ruxolitinib will receive simtuzumab 700 mg for at least 24 weeks. Treatment could be continued if there is evidence of clinical benefit as judged by the treating physician. |
| GS-6624 125mg | EXPERIMENTAL | - |
| Experimental: GS-6624 200mg | EXPERIMENTAL | - |
| AB0024 | EXPERIMENTAL | The starting dose for Part A will be 1 mg/kg. Subsequent doses of 3, 10, and 20 mg/kg are planned. Three to 6 patients will be enrolled using a 3 + 3 design. Doses of AB0024 will be administered on Days 1, 15, 29, and 43 to characterize the safety, tolerability, and PK. The dose expansion phase of the study will begin upon completion of the dose escalation phase. Up to 20 patients will be enrolled into one or two cohorts of Part B. The first expansion cohort will be dosed up to the MTD defined as the highest dose level with an observed incidence of DLT in \<33% of patients enrolled from Part A. |
| Name | Type | Description |
|---|---|---|
| Simtuzumab | BIOLOGICAL | Subcutaneous injections weekly for a total of 96 injections |
| Placebo | BIOLOGICAL | Subcutaneous injections weekly for a total of 96 injections |
| Gemcitabine | DRUG | Gemcitabine 1000 mg/m\^2 administered intravenously on Days 1, 8, and 15 of each 28-day cycle |
| Placebo to match simtuzumab | DRUG | Placebo to match simtuzumab administered intravenously every 2 weeks for a total of 2 infusions (Days 1 and 15) |
| Ruxolitinib | DRUG | In Stage 2, participants will be on a stable dose of ruxolitinib |
| GS-6624 | DRUG | Patients will be treated with GS-6624 (125 or 200 mg) administered IV over 1 hour on specific days during the treatment period. |
| AB0024 | DRUG | Comparison of different dosages of drug |
Key Inclusion Criteria: * Adult Individuals (aged 18-70) with chronic cholestatic liver disease of at least 6 months. * Liver biopsy consistent with PSC: If a liver biopsy has been performed within 3 months of the screening visit, tissue from that biopsy may be used as the screening biopsy. Slides ...
Simtuzumab is an investigational monoclonal antibody developed by Gilead Sciences, Inc. (ticker GILD) that targets LOXL2. It was studied in Phase 2 clinical trials for liver fibrosis, myelofibrosis, pancreatic cancer, and primary sclerosing cholangitis (PSC). It is not an approved therapy and remains in clinical development.
Simtuzumab targets LOXL2, a lysyl oxidase-like enzyme involved in collagen cross-linking and tissue remodeling. It is classified as an inhibitor of LOXL2. By binding this target, simtuzumab was designed to interfere with the fibrotic process, which is why it was studied in liver fibrosis and related conditions.
Simtuzumab was studied for liver fibrosis, primary sclerosing cholangitis (PSC), pancreatic cancer, and myelofibrosis. It is an investigational agent and is not approved for any indication. All of its recorded Phase 2 trials have been completed, and no trials are currently active.
Simtuzumab is developed by Gilead Sciences, Inc., which trades under the ticker GILD. Gilead sponsored the Phase 2 clinical program evaluating the monoclonal antibody across liver fibrosis, primary sclerosing cholangitis, pancreatic cancer, and myelofibrosis.
Simtuzumab is in Phase 2. Its clinical program includes completed Phase 2 trials, and no active trials are ongoing. The drug is investigational and has not been approved by the FDA for any indication.
Simtuzumab has been evaluated in completed Phase 2 trials including NCT01707472 in HIV and/or hepatitis C infected adults with liver fibrosis, NCT01672853 in primary sclerosing cholangitis, NCT01472198 combined with gemcitabine for metastatic pancreatic adenocarcinoma, and NCT01452308 in liver fibrosis.