A Randomized, Double-Blind, Placebo-Controlled, Two-Arm Parallel Group, Multi-Center Phase 3 Pivotal Trial to Investigate the Efficacy and Safety of Recombinant Human Alkaline Phosphatase for Treatment of Patients with Sepsis-Associated Acute Kidney Injury

AM-Pharma B.V.0 sites1,600 target enrollmentStarted: July 28, 2020Last updated: May 30, 2022

Trial Snapshot

Phase: Phase 1
Status: Active, not recruiting
Sponsor
Enrollment: 1,600

Study Overview Eligibility Criteria Investigators Records & Identifiers Similar Trials

Study Overview

Brief Summary

No summary available.

Study Design

Study Type: Interventional clinical trial of medicinal product

Eligibility Criteria

Sex: All

Inclusion Criteria

•To be eligible for this trial, a patient must meet all of the following inclusion criteria:
•1. 18 years or older.
•2. In the ICU or intermediate care unit for clinical reasons.
•3. Have sepsis requiring vasopressor (norepinephrine, epinephrine, dopamine, phenylephrine, vasopressin, or angiotensin II) therapy, i.e.:
•a) suspected or proven bacterial or viral infection and
•b) on vasopressor therapy (=0.1 µg/kg/min norepinephrine or equivalent) for sepsis-induced hypotension for at least one hour despite adequate fluid resuscitation according to clinical judgement. Following the initial one hour on at least 0.1 µg/kg/min norepinephrine or equivalent, any dose of vasopressor counts as vasopressor therapy.
•4. Have AKI according to at least one of the below Kidney Disease Improving Global Outcomes (KDIGO) criteria, a) to d):
•a) An absolute increase in serum or plasma creatinine (CR) by =0.3 mg/dL (=26.5 µmol/L) within 48 hours or
•b) A relative increase in CR to =1.5 times pre-AKI reference CR value (see Section 8.3.3.3), which is known or presumed to have occurred within prior 7 days or
•c) A decrease in urinary output to <0.5 mL/kg/hour for a minimum of 6 hours following adequate fluid resuscitation or
•d) If the patient does not have a known history of CKD and there is no pre-AKI reference CR value (see Section 8.3.3.3) available from the past 12 months: a CR value greater or equal to the levels presented in Table 1, with the increase in CR presumed to have occurred within prior 7 days. For Table 1, please refer to the Protocol.
•5. Provision of signed and dated informed consent form (ICF) in accordance with local regulations.
•Are the trial subjects under 18? no
•Number of subjects for this age range:
•F.1.2 Adults (18-64 years) yes
•F.1.2.1 Number of subjects for this age range 900
•F.1.3 Elderly (>=65 years) yes
•F.1.3.1 Number of subjects for this age range 700

Exclusion Criteria

•A patient who meets any of the following criteria is excluded from participation in this trial:
•1. Documented CKD as specified below:
•a) At selected sites where enrolment of 'moderate' CKD patients is allowed, patients with 'severe' CKD defined as a pre-AKI reference eGFR <25 mL/min/1.73 m2 are excluded.
•- For patients with known CKD, the most recent eGFR prior to index hospitalization needs to be documented as =25 mL/min/1.73 m2.
•- For patients with known CKD but no known eGFR prior to hospitalization, presentation eGFR between 25-60 mL/min/1.73 m2 can also be used to rule out ‘severe’ CKD.
•b) At sites where enrolment of 'moderate' CKD patients is NOT allowed, patients with 'moderate' and 'severe' CKD defined as a pre-AKI reference eGFR <45 mL/min/1.73 m2 are excluded.
•- For patients with known CKD, the most recent eGFR prior to index hospitalization needs to be documented as =45 mL/min/1.73 m2.
•- For patients with known CKD but no known eGFR prior to hospitalization, presentation eGFR between 45-60 mL/min/1.73 m2 can also be used to rule out 'moderate' and 'severe' CKD.
•2. Advanced chronic liver disease, defined as a Child-Pugh score of 10 to 15 (Class C).
•3. Acute pancreatitis without proven infection.
•4. Urosepsis related to suspected or proven urinary tract obstruction.
•5. Main cause of AKI not sepsis.
•6. Proven or suspected SARS-CoV-2 infection. This exclusion criterion does not apply to patients in the COVID-19 population in which COVID-
•19 should be the main cause of SA-AKI.
•7. Severe burns requiring ICU treatment.
•8. Severely immunosuppressed, e.g. due to:
•- hematopoietic cell transplantation within past 6 months prior to Screening or acute or chronic graft-versus-host disease
•- solid organ transplantation
•- leukopenia not related to sepsis, i.e., preceding sepsis
•- Human Immunodeficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS)
•- receiving chemotherapy within 30 days prior to Screening.
•9. At high risk of being lost to follow-up (LTFU), e.g., due to known current or recent (within the last 6 months) IV drug abuse or known to be homeless.
•10. Limitations to use of MV, RRT or vasopressors and inotropes (NOTE: limitation of cardiopulmonary resuscitation (CPR) only is not an exclusion criterion).
•11. Previous administration of recAP.
•12. Use of a non-marketed drug within the last month or concurrent or planned participation in a clinical trial for a non-marketed drug or device. (NOTE: Co-enrollment or concurrent participation in observational, non-interventional trials using no protocolized treatments or procedures are always allowed. Co-enrollment or concurrent participation in trials using protocolized treatments or procedures, e.g. blood draws, requires pre-approval by the TSC).
•13. Current or planned extracorporeal membrane oxygenation (ECMO).
•14. On RRT >24 hours before start of trial drug.
•15. No longer on vasopressor therapy at time of randomization.
•16. On continuous vasopressor therapy for >72 hours before start of trial drug.
•17. Estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m2 based on the most recent available CR sample at time of screening (NOTE: will often be the sample used to diagnose AKI). eGFR should be calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. In Japan, the CKD-EPI formula with Japanese coefficient should be used. If local regulations prohibit correcting for race in the calculation of eGFR, it is acceptable to use th

Investigators

Sponsor

AM-Pharma B.V.

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