NCT04411472

(Revival) Study to Investigate the Efficacy and Safety of Alkaline Phosphatase in Patients With Sepsis-Associated AKI

A DB, Placebo-Controlled, Two-Arm Parallel-Group, Phase 3 RCT to Investigate the Efficacy and Safety of Recombinant Human Alkaline Phosphatase for Treatment of Patients With SA-AKI

• Status: Terminated
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 676 (actual)
• Sponsor: AM-Pharma · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Clinical phase 3 study to investigate the effect of recAP on 28 day mortality in patients admitted to the ICU with acute kidney injury that is caused by sepsis. The study has three distinct SA-AKI trial populations: 1. The main trial population: Patients with a pre-AKI reference eGFR ≥45 mL/min/1.73 m2 and no proven or suspected SARS-CoV-2 at time of randomization. 2. A 'moderate' CKD population: Patients with a pre-AKI reference eGFR ≥25 and \<45 mL/min/1.73 m2 and no proven or suspected SARS-CoV-2 at time of randomization. 3. A Corona Virus Disease 2019 (COVID-19) population: Patients with proven or suspected SARS-CoV-2 at time of randomization with or without 'moderate' CKD. For patients in this population, COVID-19 should be the main cause of SA-AKI. In the main study population approximately 1400 patients will be enrolled and in the two cohorts with moderate CKD and COVID-19 each up to 100 patients. There are two arms in the study, one with active treatment and one with an inactive compound (placebo). Treatment is by 1 hour intravenous infusion, for three days. Patients are followed up for 28 days to see if there is an improvement on mortality, and followed for 90 and 180 days for mortality and other outcomes e.g. long-term kidney function and quality of life.

Detailed description

Sepsis is the leading cause of acute kidney injury (AKI) and a major cause of death. Patients with SA-AKI have a high mortality and morbidity and are at risk of developing chronic kidney disease. AP is a homodimeric endogenous enzyme present in many cells and organs, e.g., intestines, placenta, liver, bone, kidney, and granulocytes. It exerts detoxifying effects through dephosphorylation of endotoxins; pathogen associated molecular pattern molecules (PAMPS e.g., lipopolysaccharide) and damage-associated molecular pattern molecules (DAMPS e.g., adenosine tri- and di-phosphate). In animal models of sepsis and AKI, administration of AP attenuates the inflammatory response, improves renal function and/or reduces mortality. AM-Pharma B.V. is developing AP as a novel, recombinant chimeric human AP medicinal product, called recAP, to be used as an intravenous infusion for the treatment of SA-AKI. In the Phase 2 trial STOP-AKI, a survival benefit was observed in the two highest dose groups, 0.8 mg/kg and 1.6 mg/kg groups, compared to the placebo group. There were no safety or tolerability concerns for any of the doses tested (0.4, 0.8 and 1.6 mg/kg). The 1.6 mg/kg recAP dose was selected for this Phase 3 trial based on the significant survival benefit observed. PK/PD simulations also confirmed this dose to have the most pronounced treatment effect. The primary objective of this Phase 3 trial is to confirm the mortality benefit seen in STOP-AKI by demonstrating a reduction in 28 day all cause mortality in patients with SA-AKI treated with 1.6 mg/kg recAP.

Conditions

• Acute Kidney Injury Due to Sepsis

Interventions

Type	Name	Description
BIOLOGICAL	Recombinant human alkaline phosphatase	patients with SA-AKI are randomly assigned in a 1:1 ratio to either placebo or 1.6 mg/kg recAP.
OTHER	Placebo	Placebo

Timeline

• Start date: 2020-11-02
• Primary completion: 2022-08-18
• Completion: 2022-08-18
• First posted: 2020-06-02
• Last updated: 2024-06-03
• Results posted: 2024-06-03

Locations

122 sites across 15 countries: United States, Australia, Austria, Belgium, Canada, Denmark, Finland, France, Germany, Ireland, Japan, Netherlands, New Zealand, Spain, United Kingdom

Regulatory

• FDA-regulated drug study