Beslissing van de eerste vooraf gespecificeerde futiliteitsanalyse bij 400 patiënten wordt in juli verwacht
UTRECHT, Nederland–(BUSINESS WIRE)– AM-Pharma B.V., een opkomende leider die zich richt op het ontwikkelen van therapieën voor ernstige medische aandoeningen, heeft vandaag aangekondigd dat 400 patiënten nu zijn opgenomen in de belangrijkste onderzoekspopulatie van de cruciale fase 3 REVIVAL-studie. De REVIVAL-studie evalueert AM-Pharma’s gepatenteerde recombinante alkalische fosfatase, ilofotase alfa, voor de behandeling van patiënten met sepsis-geassocieerd acuut nierletsel (SA-AKI). Volgens het onderzoeksprotocol zullen vier tussentijdse analyses voor nutteloosheid en/of werkzaamheid worden uitgevoerd wanneer de inschrijving bepaalde niveaus bereikt en de eerste futiliteit analyse zal plaatsvinden wanneer 400 patiënten in de hoofdonderzoek populatie zijn behandeld en dag 28 hebben bereikt.
400 Patients Have Been Enrolled in AM-Pharma’s Pivotal Phase 3 Study of Ilofotase Alfa for the Treatment of Sepsis-associated Acute Kidney Injury
Decision from the first pre-specified futility analysis at 400 patients is expected in July
UTRECHT, The Netherlands–(BUSINESS WIRE)– AM-Pharma B.V., an emerging leader focused on developing therapeutics for severe medical conditions, today announced that 400 patients have now been enrolled in the main trial population in the pivotal Phase 3 REVIVAL study. The REVIVAL study is evaluating AM-Pharma’s proprietary recombinant alkaline phosphatase, ilofotase alfa, for the treatment of patients with sepsis-associated acute kidney injury (SA-AKI). Per the study protocol, four interim analyses for futility and/or efficacy will be conducted when enrollment hits certain levels and the first futility analysis will occur when 400 patients in the main trial population have been treated and have reached day 28.
The primary endpoint of the study is all-cause mortality 28 days post-treatment start. Once the first 400 patients enrolled in the main study population in the study reach the 28-day primary endpoint, the blinded data will be analyzed and sent to the data monitoring committee (DMC) for review. The DMC will then evaluate for futility based on pre-defined criteria. The company anticipates that the DMC futility decision will be available in July.
“Hitting this first enrollment threshold in REVIVAL is a significant achievement for our company and we look forward to receiving the futility assessment from the DMC,” said Erik van den Berg, Chief Executive Officer of AM-Pharma. “There are three additional futility/efficacy analyses scheduled at the 700, 850 and 1,000 patient thresholds. We see each of these interim analyses as de-risking to the program and, importantly, as potential events that could enable us to stop the study for efficacy and expedite the time to market for ilofotase alfa.”
In the Phase II study of ilofotase alfa, the comparable patient group treated with the 1.6mg/kg dose experienced a statistically significant 46% relative reduction in mortality at day 28 compared to the group treated with placebo (p= 0.022). REVIVAL, the single global pivotal Phase III study of ilofotase alfa in SA-AKI patients, was initiated in November 2020 and is enrolling patients at up to about 120 clinical sites in North America, Europe, Japan, Australia and New Zealand. The U.S. Food and Drug Administration, European Medicines Agency and Japanese Pharmaceuticals and Medical Devices Agency have all approved the REVIVAL protocol.
The REVIVAL Phase III pivotal trial is a randomized, double-blind, placebo-controlled, two-arm, parallel-group, multi-center trial to evaluate the efficacy and safety of AM-Pharma’s proprietary human recombinant alkaline phosphatase, ilofotase alfa, for the treatment of patients with SA-AKI. The study will enroll approximately 1400 patients with SA-AKI in the main study population. In two exploratory cohorts, up to 100 patients with moderate Chronic Kidney Disease (CKD) and up to 100 patients with COVID-19 will also be enrolled. Patients in the study will be randomized to receive 1.6mg/kg of ilofotase alfa or placebo. The primary aim of the study is to confirm the improvement on the primary endpoint of 28-day all-cause mortality, as observed in the Phase II STOP-AKI study. Secondary endpoints include the treatment effect on long-term Major Adverse Kidney Events (MAKE), on the use of organ support, length of stay in the ICU and on 90-day all-cause mortality. Further information on this study can be found at www.clinicaltrials.gov, NCT04411472 (REVIVAL).
About Ilofotase Alfa
Ilofotase alfa is a proprietary recombinant alkaline phosphatase, constructed from two human isoforms of alkaline phosphatase, that in multiple clinical trials was shown to be stable and highly active. The recombinant enzyme displays exquisite activity towards dephosphorylating and detoxifying damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide (LPS), ATP, ADP and other extracellular substrates that drive acute inflammation, coagulation and microvascular ischemia found in kidney following sepsis or ischemia-induced damage. Research has shown that ATP dephosphorylation has a double effect in protecting against kidney injury. When the pro-inflammatory ATP is dephosphorylated, the resulting adenosine further reduces inflammation through the activation of the immunosuppressive adenosine A2a receptor pathway.
AM-Pharma’s purpose is to save and improve the lives of patients confronted with severe medical conditions. Our initial focus is sepsis-associated acute kidney injury, the cause of death for hundreds of thousands of people hospitalized each year. Our proprietary compound, ilofotase alfa, has the potential to become the first treatment for sepsis-associated acute kidney injury and is now in a global pivotal Phase III clinical trial. We are a dedicated team driven to bring treatment options to severely ill patients, their families and acute care professionals. Find out more about us online at: www.am-pharma.com.