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

Phase 3

Completed

• Conditions: Acute kidney injury associated with sepsis; sudden kidney injury due to sepsis; 10029149

• Registration Number: NL-OMON55312
• Lead Sponsor: AM-Pharma B.V.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 160

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.

5. Provision of signed and dated informed consent form (ICF) in accordance with
local regulations.

Exclusion Criteria

1. At sites where enrolment of *moderate* CKD patients is allowed:
a) 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.

At sites:
b) 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 us

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>28-day all-cause mortality</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>1. MAKE 90: dead by day 90 or on Renal Replacement Therapy (RRT) at day 90 or<br /><br>>=25% decline in estimated glomerular filtration rate (eGFR) on both day 28 and<br /><br>Day 90 relative to the known or assumed pre-AKI reference level.<br /><br><br /><br>2. Days alive and free of organ support through Day 28, i.e., days alive with<br /><br>no MV, RRT, vasopressors or inotropes (with death within 28 days counting as<br /><br>zero days).<br /><br><br /><br>3. Days alive and out of the ICU through Day 28 (with death within 28 days<br /><br>counting as zero days).<br /><br><br /><br>4. Time to death through Day 90.</p><br>