Phase 3 Study of Reltecimod vs Placebo in Patients With Sepsis-associated Acute Kidney Injury

Phase 3 Randomized, Double-blind Study to Evaluate the Safety and Efficacy of Reltecimod as Compared to Placebo in Addition to Standard of Care in Patients With Sepsis-associated Acute Kidney Injury (SA-AKI)

Phase 3 multicenter study to be conducted in up to 90 qualified participating sites globally to assess the efficacy and safety of Reltecimod vs placebo in patients with sepsis-associated Stage 2/3 AKI.

Phase 3 randomized, placebo controlled study assessing the efficacy (complete recovery from AKI) and safety of Reltecimod in patients with suspected or confirmed abdominal sepsis (planned or completed surgical (laparotomy or laparoscopy) or interventional radiologic procedures for control of underlying abdominal infection within 24 hours of evaluation by medical personnel) or patients with surgically confirmed necrotizing soft tissue infection (NSTI), requiring intensive care unit (ICU) or step down unit admission and in whom the diagnosis of Stage 2/3 acute kidney injury (AKI; as defined by Kidney Disease Improving Global Outcomes (KDIGO) criteria) is established at initial presentation for medical evaluation or up to 48 hours from the suspected diagnosis of abdominal sepsis or from surgically confirmed diagnosis of NSTI.

Inclusion Criteria:

1. Has either suspected or documented diagnosis of abdominal sepsis requiring treatment with parenteral antibiotics and planned or completed surgical (laparotomy or laparoscopy) or interventional radiologic procedures within 24 hours of evaluation by medical personnel. Recommended surgical or interventional radiologic procedures be performed with 12 hours of evaluation by medical personnel.

2. Initial diagnosis of AKI Stage 2 or 3 according to KDIGO AKI criteria established either upon presentation to medical care in those patients with suspected abdominal sepsis or in those patients in whom the initial diagnosis of AKI is established during the 48 hour period from the suspected diagnosis of abdominal sepsis.

3. Study medication must be administered within 6 hours of confirmation of onset of Stage 2 or 3 AKI as established at the study site, under the following criteria:

   • After the decision is made by the attending surgeon at the study site for a surgical or interventional radiology procedure for the abdominal infection OR
   • After confirmed diagnosis of abdominal infection has been established by a surgical or interventional radiology procedure

Exclusion Criteria:

1. Has known prior history of chronic kidney disease (CKD( with a documented estimated GFR (eGFR) < 30 mL/min

   • Exception: Patients with history of CKD but no available prior eGFR who have documented normal kidney size on ultrasound or computed tomography evaluation (performed within 90 days of screening) will be eligible

2. Patients receiving renal replacment therapy (RRT) for CKD

3. . Previously diagnosed with documented AKI in the last 30 days

4. Documented primary glomerular disease or toxic tubulo-interstitial nephritis at the time of AKI diagnosis

5. Patient is not expected to survive throughout 28 days of study due to significant underlying medical condition

6. Any concurrent medical condition, which in the opinion of the Investigator, may compromise the safety of the patient or the objectives of the study or the patient will not benefit from treatment such as:

   • Congestive heart failure (CHF) {New York Heart Association (NYHA) class III-IV}
   • Severe chronic obstructive pulmonary disease (COPD) {GOLD - Global Initiative for Chronic Obstructive Lung Disease - stage IV. or chronic hypoxemia)
   • Liver dysfunction {Childs-Pugh class C}
   • Primary or acquired immunodeficiency or immunosuppression due to treatment with immunosuppressive medications
   • Known HIV infection with CD4 count < 200 cells/mm3 or < 14% of all lymphocytes
   • Neutropenia < 1,000 cells/mm3 not due to the underlying infection
   • Receiving or about to receive chemotherapy or biologic anti-cancer treatment,
   • Hematological and lymphatic malignancies in the last 5 years

7. Patient has acute pancreatitis with no established source of infection, uncomplicated appendicitis, or cholangitis or cholecystitis without peritonitis;

8. Pregnant or lactating women

9. Concurrent or previous enrollment in a clinical trial involving investigational drug or a medical device