NCT02182440

A Safety, Tolerability, Efficacy and QoL Study of Human recAP in the Treatment of Patients With SA-AKI

A DB Four-Arm, Parallel Group, Proof of Concept, Dose-Finding Adaptive Phase 2a/2b RCT to Investigate the Safety, Tolerability and Efficacy and Effect on QoL of Human Recombinant Alkaline Phosphatase in Patients With Sepsis-Associated AKI

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 301 (actual)
• Sponsor: AM-Pharma · Industry
• Sex: All
• Age: 18 Years – 85 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to determine whether recombinant Alkaline Phosphatase (recAP) is effective and save, and to determine the most effective dose, in the treatment of patients with acute kidney injury caused by sepsis.

Detailed description

Design: Adaptive trial with two stages and interim analysis * Stage 1: four arms; three dose groups and placebo. n=30/arm. (n=120) * Interim analysis based on 120 subjects, with continued recruitment, adding 11 subjects to Stage 1 safety population (n=131): to evaluate safety and select dose for stage 2 * Stage 2: one dose group and placebo. N=85/arm. (n=170) Total n in the study: 301. Primary objectives * To investigate the effect of recAP on renal function (measured creatinine clearance D1-D7 period, incidence and duration of renal replacement therapy (RRT) over 28 days, eGFR at D60 and D90) and related clinical parameters (ICU stay, Hospital stay, Mechanical ventilation over 28 days, SOFA and SAPS2 scores 28 days) in patients with SA-AKI. * To determine effective therapeutic dose(s) of recAP. Secondary objectives * To investigate the safety and tolerability of recAP in patients with SA AKI. (assessed by independent Data Monitoring Board, adverse events over 90 days study period, laboratory values, ECG, physical examniations, vital signs, Anti Drug Antibodies) * To investigate the pharmacokinetic profile (PK) of recAP in a subset of patients (part 1, n=120) with SA AKI. (Population PK; AUC D1-7, Cmax, Cmin, Tmax, terminal T1/2) * To investigate the immunogenic potential of recAP in patients with SA AKI. (anti-drug antibodies at D14, D28, D60 and D90) * To investigate the effect on quality of life (using the EuroQol, EQ-5D) following study inclusion, at ICU discharge, and Day 90. Other objectives • To evaluate whether specific patient groups can be identified that benefit most from recAP treatment or patient groups that are non-responders

Conditions

• Acute Kidney Injury

Interventions

Type	Name	Description
BIOLOGICAL	recAP	One hour infusions once daily for three days
OTHER	Placebo	1 hour IV infusion once daily for 3 days

Timeline

• Start date: 2014-12-18
• Primary completion: 2017-05-25
• Completion: 2017-09-27
• First posted: 2014-07-08
• Last updated: 2020-03-23
• Results posted: 2020-03-23

Locations

58 sites across 11 countries: United States, Austria, Belgium, Czechia, Finland, France, Germany, Ireland, Netherlands, Spain, United Kingdom