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

• Sponsor: Atox Bio Ltd (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03403751
• Collaborator: (none)
• Enrollment: 58
• Locations: 56
• Arms: 2
• Actual Duration (Months): 18.7
• Patients Per Site: 1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Kidney Injury; Peritonitis; Necrotizing Soft Tissue Infection	Drug: Reltecimod 0.5 mg/kg; Drug: Placebo	Phase 3

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 58 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: 1:1 randomization of study drug (Reltecimod) and placebo (normal saline)1:1 randomization of study drug (Reltecimod) and placebo (normal saline)
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Sponsor personnel and clinical research associates (CRAs) will also be blinded to study treatment.
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: May 24, 2018
• Actual Primary Completion Date: Dec 14, 2019
• Actual Study Completion Date: Dec 14, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Reltecimod 0.5 mg/kg Single IV infusion of Reltecimod 0.5 mg/kg	Drug: Reltecimod 0.5 mg/kg; Single IV infusion of 0.5 mg/kg Reltecimod (at a concentration of 1 mg/mL) over approximately 10 minutes; Other Names: AB103 0.5 mg/kg
Placebo Comparator: Placebo Single IV infusion of 0.9% Sodium Chloride Injection (Normal Saline)	Drug: Placebo; Single IV infusion of 0.5 mL/kg of 0.9% saline (volume equivalent to Reltecimod dosing schema) over approximately 10 minutes; Other Names: 0.9% Sodium Chloride Injection (Normal saline)

Outcome Measures

Primary Outcome Measures

1. Freedom From Durable Loss of Renal Function at Day 28 [28 Days]

   Freedom from durable loss of renal function at Day 28 required all of the following 3 components: alive at Day 28, free of dialysis at Day 28, and less than 37% loss of estimated glomerular filtration rate (eGFR) at Day 28 from patient reference eGFR (measured by Modification of Diet in Renal Disease [MDRD] formula).

2. Serious Adverse Events (SAEs) [28 Days]

   Number of patients experiencing at least one SAE

3. Adverse Events (AEs) [28 Days]

   The number of patients experiencing at least one AE.

Secondary Outcome Measures

1. Freedom From Durable Loss of Renal Function at Day 14 [14 Days]

   Freedom from durable loss of renal function at Day 14 required all of the following 3 components: alive at Day 14, free of dialysis at Day 14, and less than 37% loss of estimated glomerular filtration rate (eGFR) at Day 14 from patient reference eGFR (measured by Modification of Diet in Renal Disease [MDRD] formula).

2. Intensive Care Unit (ICU)-Free Days [28 Days]

   ICU-free days refers to the number of days a patient did not spend time in the ICU through Day 28.

3. Ventilator-free Days [28 Days]

   Ventilator-free days refers to the number of days a patient was not on a ventilator through Day 28.

4. Vasopressor-free Days [28 Days]

   Vasopressor-free days refers to the number of days a patient did not receive a vasopressor through Day 28.

5. Hospital Days [90 Days]

   Hospital days refers to the number of days a patient spent time in the hospital.

6. Cumulative Number of Deaths [90 Days]

   The number of deaths occurring through Day 90

7. Secondary Infections [28 Days]

   Number of patients experiencing at least one secondary infection

8. ICU-free Days by Day 14 Modified Sequential Organ Failure Assessment (mSOFA) Category [28 Days]

   The number of days a patient did not spend in the ICU through Day 28, by mSOFA category (mSOFA total score of 1 or less; mSOFA total score of 2 or more). Modified Sequential Organ Failure Assessment (mSOFA) total scores range from 0 to 20, with higher scores reflecting a worse clinical status or outcome. An mSOFA total score of 0 or 1 reflects resolution of organ dysfunction/failure.

9. Ventilator-free Days by Day 14 mSOFA Category [28 Days]

   The number of days a patient was not on a ventilator through Day 28, by mSOFA category

10. Vasopressor-free Days by Day 14 mSOFA Category [28 Days]

    The number of days a patient was not receiving a vasopressor through Day 28, by mSOFA category

11. Hospital Days by Day 14 mSOFA Category [90 Days]

    The number of days a patient was in the hospital.

12. Hospital Discharge Location by Day 14 mSOFA Category [90 Days]

    Number of patients with more favorable discharge location (home or rehabilitation facility) or less favorable discharge location (skilled nursing facility, another acute care facility, death, other) among patients alive at Day 14.

Other Outcome Measures

1. Cumulative Mortality by Day 14 mSOFA Category [90 Days]

   Percentage of patients who died through Day 90 using life table analysis

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

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

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

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

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

5. 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

• 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

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

2. Pregnant or lactating women

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Maricopa Medical Center	Phoenix	Arizona	United States	85008
2	Banner University Medical Center	Tucson	Arizona	United States	24857
3	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
4	Loma Linda University Medical Center	Loma Linda	California	United States	92354
5	University of California, Davis Medical Center	Sacramento	California	United States	95817
6	UCSD Medical Center	San Diego	California	United States	92103
7	Harbor-UCLA Medical Center	Torrance	California	United States	90502
8	UCH-Memorial Health System	Colorado Springs	Colorado	United States	80909
9	University of Colorado Hospital	Denver	Colorado	United States	80045
10	Yale New Haven Hospital	New Haven	Connecticut	United States	06520
11	Washington Hospital Center	Washington	District of Columbia	United States	20010
12	UF Health Shands Hospital	Gainesville	Florida	United States	32610
13	University of Iowa Hospital and Clinics	Iowa City	Iowa	United States	52242
14	University of Kentucky	Lexington	Kentucky	United States	40536
15	LSU Health Science Center	New Orleans	Louisiana	United States	70012
16	University of Maryland, Baltimore	Baltimore	Maryland	United States	21201
17	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
18	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
19	University of Michigan	Ann Arbor	Michigan	United States	48109
20	Henry Ford Health System	Detroit	Michigan	United States	48202
21	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
22	Hennepin County Medical Center	Minneapolis	Minnesota	United States	55415
23	University of Minnesota Medical Center-Fairview	Minneapolis	Minnesota	United States	55455
24	University of Missouri	Columbia	Missouri	United States	65211
25	Capital Health System, Inc.	Trenton	New Jersey	United States	98638
26	Erie County Medical Center-Affliate of SUNYat Buffalo	Buffalo	New York	United States	14215
27	Carolinas Medical Center	Charlotte	North Carolina	United States	28208
28	East Carolina University	Greenville	North Carolina	United States	27834
29	University of Cincinnati Medical Center (UCMC)	Cincinnati	Ohio	United States	45219
30	The Ohio State University	Columbus	Ohio	United States	43210
31	Oregon Health and Science University	Portland	Oregon	United States	97239
32	St. Luke's University Health Network	Bethlehem	Pennsylvania	United States	18015
33	The Pennsylvania State University and The Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033
34	The Trauma Center at PENN	Philadelphia	Pennsylvania	United States	19104
35	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
36	MUSC	Charleston	South Carolina	United States	29425
37	John Peter Smith Health Network	Fort Worth	Texas	United States	76104
38	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229
39	Harborview Medical Center	Seattle	Washington	United States	98104
40	University of Washington Medical Center	Seattle	Washington	United States	98195
41	Hopital Victor Dupouy	Argenteuil		France
42	CHRU la Cavale Blanche	Brest		France
43	CHU Clermont-Ferrand	Clermont-Ferrand		France
44	CHU Dijon	Dijon		France
45	CHD Vendee	La Roche-sur-Yon		France
46	CH Le Mans	Le Mans		France
47	Robert Salengro Hopital-CHRU Lille	Lille		France
48	CHU de Limoges	Limoges		France
49	CHU Lyon Sud	Lyon		France
50	Hopital Edouard Herriot	Lyon		France
51	Hopital Saint Eloi	Montpellier		France
52	CHU de Nante Hotel-Dieu	Nantes		France
53	CHU Nimes	Nîmes		France
54	Hopital Cochin	Paris		France
55	CHU Rennes	Rennes		France
56	Nouvel Hopital Civil	Strasbourg		France

Sponsors and Collaborators

• Atox Bio Ltd

Investigators

• Principal Investigator: Azra Bihorac, MD, University of Florida Health

Study Documents (Full-Text)

• Study Protocol - Jul 31, 2019
• Statistical Analysis Plan - Jan 6, 2020

More Information

Publications

None provided.

• Responsible Party: Atox Bio Ltd
• ClinicalTrials.gov Identifier: NCT03403751
• Other Study ID Numbers: ATB-203
• First Posted: Jan 19, 2018
• Last Update Posted: Oct 12, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Atox Bio Ltd: Abdominal sepsis; AKI; NSTI
• Additional relevant MeSH terms: Sepsis; Peritonitis; Soft Tissue Infections; Acute Kidney Injury; Wounds and Injuries

Study Results

Participant Flow

Arm/Group Title	Reltecimod 0.5 mg/kg	Placebo
Arm/Group Description	Single IV infusion of 0.5 mg/kg Reltecimod (at a concentration of 1 mg/mL)	Single IV infusion of 0.5 mL/kg of 0.9% sodium chloride (volume equivalent with Reltecimod dosing schema)
Period Title: Overall Study
STARTED	28	30
COMPLETED	21	22
NOT COMPLETED	7	8

Baseline Characteristics

Arm/Group Title	Reltecimod 0.5 mg/kg	Placebo	Total
Arm/Group Description	Single IV infusion of 0.5 mg/kg Reltecimod (at a concentration of 1 mg/mL)	Single IV infusion of 0.5 mL/kg of 0.9% sodium chloride (volume equivalent with Reltecimod dosing schema)	Total of all reporting groups
Overall Participants	28	30	58
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.7 (14.6)	61.8 (13.6)	61.7 (14.0)
Sex: Female, Male (Count of Participants)
Female	16 57.1%	15 50%	31 53.4%
Male	12 42.9%	15 50%	27 46.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 7.1%	0 0%	2 3.4%
Not Hispanic or Latino	23 82.1%	29 96.7%	52 89.7%
Unknown or Not Reported	3 10.7%	1 3.3%	4 6.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 3.6%	4 13.3%	5 8.6%
White	23 82.1%	22 73.3%	45 77.6%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	4 14.3%	4 13.3%	8 13.8%
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	30.5 (6.9)	32.3 (12.2)	31.4 (9.9)
Disease Category (Count of Participants)
Abdominal Infection	27 96.4%	29 96.7%	56 96.6%
Necrotizing Soft Tissue Infection (NSTI)	1 3.6%	1 3.3%	2 3.4%
Comorbidities (Count of Participants)
Diabetes	11 39.3%	6 20%	17 29.3%
Cardiovascular Disease	7 25%	6 20%	13 22.4%
Smoker	1 3.6%	5 16.7%	6 10.3%
Alcohol Abuse	1 3.6%	2 6.7%	3 5.2%
Modified Sequential Organ Failure Assessment (mSOFA) Score (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	4.9 (2.3)	5.4 (3.1)	5.1 (2.8)
Acute Physiology and Chronic Health Evaluation (APACHE) Score (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	17.1 (8.5)	16.4 (7.9)	16.7 (8.2)
Sepsis Presentation (Count of Participants)
Cardiovascular Organ Failure	12 42.9%	17 56.7%	29 50%
Respiratory Organ Failure	2 7.1%	3 10%	5 8.6%
Acute Kidney Injury (AKI) Presentation (Count of Participants)
Stage 2 AKI	20 71.4%	25 83.3%	45 77.6%
Stage 3 AKI	8 28.6%	5 16.7%	13 22.4%
Acuity of AKI (Count of Participants)
AKI diagnosed at time of diagnosis of infection	17 60.7%	12 40%	29 50%
AKI diagnosed during the 48h following diagnosis of infection	11 39.3%	18 60%	29 50%

Outcome Measures

1. Primary Outcome

Title	Freedom From Durable Loss of Renal Function at Day 28
Description	Freedom from durable loss of renal function at Day 28 required all of the following 3 components: alive at Day 28, free of dialysis at Day 28, and less than 37% loss of estimated glomerular filtration rate (eGFR) at Day 28 from patient reference eGFR (measured by Modification of Diet in Renal Disease [MDRD] formula).
Time Frame	28 Days

Outcome Measure Data

Analysis Population Description

This analysis population (modified intent-to-treat [mITT]) included all randomized patients who were exposed to study drug (reltecimod or placebo) and who had a suspected or confirmed diagnosis of abdominal sepsis or confirmed necrotizing soft tissue infection (NSTI) and Stage 2 or Stage 3 AKI, with patients analyzed according to the treatment actually received.

Arm/Group Title	Reltecimod 0.5 mg/kg	Placebo
Arm/Group Description	Single IV infusion of 0.5 mg/kg Reltecimod (at a concentration of 1 mg/mL)	Single IV infusion of 0.5 mL/kg of 0.9% sodium chloride (volume equivalent with Reltecimod dosing schema)
Measure Participants	28	30
Count of Participants [Participants]	20 71.4%	23 76.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Reltecimod 0.5 mg/kg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.649
	Comments
	Method	Chi-squared
	Comments

2. Primary Outcome

Title	Serious Adverse Events (SAEs)
Description	Number of patients experiencing at least one SAE
Time Frame	28 Days

Outcome Measure Data

Analysis Population Description

This analysis population (As Treated/Safety Analysis Set) included all randomized patients who were exposed to study drug (reltecimod or placebo), with patients analyzed according to the treatment actually received.

Arm/Group Title	Reltecimod 0.5 mg/kg	Placebo
Arm/Group Description	Single IV infusion of 0.5 mg/kg Reltecimod (at a concentration of 1 mg/mL)	Single IV infusion of 0.5 mL/kg of 0.9% sodium chloride (volume equivalent with Reltecimod dosing schema)
Measure Participants	28	30
Count of Participants [Participants]	12 42.9%	13 43.3%

3. Primary Outcome

Title	Adverse Events (AEs)
Description	The number of patients experiencing at least one AE.
Time Frame	28 Days

Outcome Measure Data

Analysis Population Description

This analysis population (As Treated/Safety Analysis Set) included all randomized patients who were exposed to study drug (reltecimod or placebo), with patients analyzed according to the treatment actually received.

Arm/Group Title	Reltecimod 0.5 mg/kg	Placebo
Arm/Group Description	Single IV infusion of 0.5 mg/kg Reltecimod (at a concentration of 1 mg/mL)	Single IV infusion of 0.5 mL/kg of 0.9% sodium chloride (volume equivalent with Reltecimod dosing schema)
Measure Participants	28	30
Count of Participants [Participants]	15 53.6%	24 80%

4. Secondary Outcome

Title	Freedom From Durable Loss of Renal Function at Day 14
Description	Freedom from durable loss of renal function at Day 14 required all of the following 3 components: alive at Day 14, free of dialysis at Day 14, and less than 37% loss of estimated glomerular filtration rate (eGFR) at Day 14 from patient reference eGFR (measured by Modification of Diet in Renal Disease [MDRD] formula).
Time Frame	14 Days

Outcome Measure Data

Analysis Population Description

This analysis population (modified intent-to-treat [mITT]) included all randomized patients who were exposed to study drug (reltecimod or placebo) and who had a suspected or confirmed diagnosis of abdominal sepsis or confirmed NSTI and Stage 2 or Stage 3 AKI, with patients analyzed according to the treatment actually received.

Arm/Group Title	Reltecimod 0.5 mg/kg	Placebo
Arm/Group Description	Single IV infusion of 0.5 mg/kg Reltecimod (at a concentration of 1 mg/mL)	Single IV infusion of 0.5 mL/kg of 0.9% sodium chloride (volume equivalent with Reltecimod dosing schema)
Measure Participants	28	30
Count of Participants [Participants]	20 71.4%	22 73.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Reltecimod 0.5 mg/kg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.871
	Comments
	Method	Chi-squared
	Comments

5. Secondary Outcome

Title	Intensive Care Unit (ICU)-Free Days
Description	ICU-free days refers to the number of days a patient did not spend time in the ICU through Day 28.
Time Frame	28 Days

Outcome Measure Data

Analysis Population Description

This analysis population (modified intent-to-treat [mITT]) included all randomized patients who were exposed to study drug (reltecimod or placebo) and who had a suspected or confirmed diagnosis of abdominal sepsis or confirmed NSTI and Stage 2 or Stage 3 AKI, with patients analyzed according to the treatment actually received.

Arm/Group Title	Reltecimod 0.5 mg/kg	Placebo
Arm/Group Description	Single IV infusion of 0.5 mg/kg Reltecimod (at a concentration of 1 mg/mL)	Single IV infusion of 0.5 mL/kg of 0.9% sodium chloride (volume equivalent with Reltecimod dosing schema)
Measure Participants	28	30
Median (Full Range) [days]	24.0	21.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Reltecimod 0.5 mg/kg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.420
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

6. Secondary Outcome

Title	Ventilator-free Days
Description	Ventilator-free days refers to the number of days a patient was not on a ventilator through Day 28.
Time Frame	28 Days

Outcome Measure Data

Analysis Population Description

This analysis population (modified intent-to-treat [mITT]) included all randomized patients who were exposed to study drug (reltecimod or placebo) and who had a suspected or confirmed diagnosis of abdominal sepsis or confirmed NSTI and Stage 2 or Stage 3 AKI, with patients analyzed according to the treatment actually received.

Arm/Group Title	Reltecimod 0.5 mg/kg	Placebo
Arm/Group Description	Single IV infusion of 0.5 mg/kg Reltecimod (at a concentration of 1 mg/mL)	Single IV infusion of 0.5 mL/kg of 0.9% sodium chloride (volume equivalent with Reltecimod dosing schema)
Measure Participants	28	30
Median (Full Range) [days]	26.5	26.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Reltecimod 0.5 mg/kg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.448
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

7. Secondary Outcome

Title	Vasopressor-free Days
Description	Vasopressor-free days refers to the number of days a patient did not receive a vasopressor through Day 28.
Time Frame	28 Days

Outcome Measure Data

Analysis Population Description

This analysis population (modified intent-to-treat [mITT]) included all randomized patients who were exposed to study drug (reltecimod or placebo) and who had a suspected or confirmed diagnosis of abdominal sepsis or confirmed NSTI and Stage 2 or Stage 3 AKI, with patients analyzed according to the treatment actually received.

Arm/Group Title	Reltecimod 0.5 mg/kg	Placebo
Arm/Group Description	Single IV infusion of 0.5 mg/kg Reltecimod (at a concentration of 1 mg/mL)	Single IV infusion of 0.5 mL/kg of 0.9% sodium chloride (volume equivalent with Reltecimod dosing schema)
Measure Participants	28	30
Median (Full Range) [days]	27.5	26.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Reltecimod 0.5 mg/kg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.579
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

8. Secondary Outcome

Title	Hospital Days
Description	Hospital days refers to the number of days a patient spent time in the hospital.
Time Frame	90 Days

Outcome Measure Data

Analysis Population Description

This analysis population (modified intent-to-treat [mITT]) included all randomized patients who were exposed to study drug (reltecimod or placebo) and who had a suspected or confirmed diagnosis of abdominal sepsis or confirmed NSTI and Stage 2 or Stage 3 AKI, with patients analyzed according to the treatment actually received.

Arm/Group Title	Reltecimod 0.5 mg/kg	Placebo
Arm/Group Description	Single IV infusion of 0.5 mg/kg Reltecimod (at a concentration of 1 mg/mL)	Single IV infusion of 0.5 mL/kg of 0.9% sodium chloride (volume equivalent with Reltecimod dosing schema)
Measure Participants	28	30
Median (Full Range) [days]	9.0	13.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Reltecimod 0.5 mg/kg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.227
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

9. Secondary Outcome

Title	Cumulative Number of Deaths
Description	The number of deaths occurring through Day 90
Time Frame	90 Days

Outcome Measure Data

Analysis Population Description

This analysis population (modified intent-to-treat [mITT]) included all randomized patients who were exposed to study drug (reltecimod or placebo) and who had a suspected or confirmed diagnosis of abdominal sepsis or confirmed NSTI and Stage 2 or Stage 3 AKI, with patients analyzed according to the treatment actually received.

Arm/Group Title	Reltecimod 0.5 mg/kg	Placebo
Arm/Group Description	Single IV infusion of 0.5 mg/kg Reltecimod (at a concentration of 1 mg/mL)	Single IV infusion of 0.5 mL/kg of 0.9% sodium chloride (volume equivalent with Reltecimod dosing schema)
Measure Participants	28	30
Count of Participants [Participants]	5 17.9%	6 20%

10. Secondary Outcome

Title	Secondary Infections
Description	Number of patients experiencing at least one secondary infection
Time Frame	28 Days

Outcome Measure Data

Analysis Population Description

This analysis population (As Treated/Safety Analysis Set) included all randomized patients who were exposed to study drug (reltecimod or placebo), with patients analyzed according to the treatment actually received.

Arm/Group Title	Reltecimod 0.5 mg/kg	Placebo
Arm/Group Description	Single IV infusion of 0.5 mg/kg Reltecimod (at a concentration of 1 mg/mL)	Single IV infusion of 0.5 mL/kg of 0.9% sodium chloride (volume equivalent with Reltecimod dosing schema)
Measure Participants	28	30
Count of Participants [Participants]	4 14.3%	10 33.3%

11. Secondary Outcome

Title	ICU-free Days by Day 14 Modified Sequential Organ Failure Assessment (mSOFA) Category
Description	The number of days a patient did not spend in the ICU through Day 28, by mSOFA category (mSOFA total score of 1 or less; mSOFA total score of 2 or more). Modified Sequential Organ Failure Assessment (mSOFA) total scores range from 0 to 20, with higher scores reflecting a worse clinical status or outcome. An mSOFA total score of 0 or 1 reflects resolution of organ dysfunction/failure.
Time Frame	28 Days

Outcome Measure Data

Analysis Population Description

This analysis population (modified intent-to-treat [mITT]) included all randomized patients who were exposed to study drug (reltecimod or placebo) and who had a suspected or confirmed diagnosis of abdominal sepsis or confirmed NSTI and Stage 2 or Stage 3 AKI, with patients analyzed according to the treatment actually received. Only patients with available mSOFA data are included in the analysis.

Arm/Group Title	Day 14 mSOFA <= 1	Day 14 mSOFA >= 2
Arm/Group Description	mSOFA total score on Day 14 of 0 or 1	mSOFA total score on Day 14 of at least 2
Measure Participants	26	10
Median (Full Range) [days]	24.0	4.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Reltecimod 0.5 mg/kg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

12. Secondary Outcome

Title	Ventilator-free Days by Day 14 mSOFA Category
Description	The number of days a patient was not on a ventilator through Day 28, by mSOFA category
Time Frame	28 Days

Outcome Measure Data

Analysis Population Description

This analysis population (modified intent-to-treat [mITT]) included all randomized patients who were exposed to study drug (reltecimod or placebo) and who had a suspected or confirmed diagnosis of abdominal sepsis or confirmed NSTI and Stage 2 or Stage 3 AKI, with patients analyzed according to the treatment actually received. Only patients with available mSOFA data are included in the analysis.

Arm/Group Title	Day 14 mSOFA <= 1	Day 14 mSOFA >= 2
Arm/Group Description	mSOFA total score on Day 14 of 0 or 1	mSOFA total score on Day 14 of at least 2
Measure Participants	26	10
Median (Full Range) [days]	27.0	17.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Reltecimod 0.5 mg/kg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

13. Secondary Outcome

Title	Vasopressor-free Days by Day 14 mSOFA Category
Description	The number of days a patient was not receiving a vasopressor through Day 28, by mSOFA category
Time Frame	28 Days

Outcome Measure Data

Analysis Population Description

This analysis population (modified intent-to-treat [mITT]) included all randomized patients who were exposed to study drug (reltecimod or placebo) and who had a suspected or confirmed diagnosis of abdominal sepsis or confirmed NSTI and Stage 2 or Stage 3 AKI, with patients analyzed according to the treatment actually received. Only patients with available mSOFA data are included in the analysis.

Arm/Group Title	Day 14 mSOFA <= 1	Day 14 mSOFA >= 2
Arm/Group Description	mSOFA total score on Day 14 of 0 or 1	mSOFA total score on Day 14 of at least 2
Measure Participants	26	10
Median (Full Range) [days]	28.0	18.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Reltecimod 0.5 mg/kg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

14. Secondary Outcome

Title	Hospital Days by Day 14 mSOFA Category
Description	The number of days a patient was in the hospital.
Time Frame	90 Days

Outcome Measure Data

Analysis Population Description

This analysis population (modified intent-to-treat [mITT]) included all randomized patients who were exposed to study drug (reltecimod or placebo) and who had a suspected or confirmed diagnosis of abdominal sepsis or confirmed NSTI and Stage 2 or Stage 3 AKI, with patients analyzed according to the treatment actually received. Only patients with available mSOFA data are included in the analysis.

Arm/Group Title	Day 14 mSOFA <= 1	Day 14 mSOFA >= 2
Arm/Group Description	mSOFA total score on Day 14 of 0 or 1	mSOFA total score on Day 14 of at least 2
Measure Participants	26	10
Median (Full Range) [days]	13.0	23.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Reltecimod 0.5 mg/kg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.007
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

15. Secondary Outcome

Title	Hospital Discharge Location by Day 14 mSOFA Category
Description	Number of patients with more favorable discharge location (home or rehabilitation facility) or less favorable discharge location (skilled nursing facility, another acute care facility, death, other) among patients alive at Day 14.
Time Frame	90 Days

Outcome Measure Data

Analysis Population Description

This analysis population (modified intent-to-treat [mITT]) included all randomized patients who were exposed to study drug (reltecimod or placebo) and who had a suspected or confirmed diagnosis of abdominal sepsis or confirmed NSTI and Stage 2 or Stage 3 AKI, with patients analyzed according to the treatment actually received. Only patients alive at Day 14 with available data are included in the analysis.

Arm/Group Title	Day 14 mSOFA <= 1	Day 14 mSOFA >= 2
Arm/Group Description	mSOFA total score on Day 14 of 0 or 1	mSOFA total score on Day 14 of at least 2
Measure Participants	38	12
More Favorable Discharge Location	28 100%	4 13.3%
Less Favorable Discharge Location	10 35.7%	8 26.7%

16. Other Pre-specified Outcome

Title	Cumulative Mortality by Day 14 mSOFA Category
Description	Percentage of patients who died through Day 90 using life table analysis
Time Frame	90 Days

Outcome Measure Data

Analysis Population Description

This analysis population (modified intent-to-treat [mITT]) included all randomized patients who were exposed to study drug (reltecimod or placebo) and who had a suspected or confirmed diagnosis of abdominal sepsis or confirmed NSTI and Stage 2 or Stage 3 AKI, with patients analyzed according to the treatment actually received. Only patients with a screening mSOFA >= 3 are included in the analysis.

Arm/Group Title	Day 14 mSOFA <= 1	Day 14 mSOFA >= 2
Arm/Group Description	mSOFA total score on Day 14 of 0 or 1	mSOFA total score on Day 14 of at least 2
Measure Participants	26	10
Number [percentage of patients]	0	31.4

Adverse Events

Time Frame	Adverse events (AEs) reported here were collected from study drug administration through the Day 29 visit (28 days after study drug dosing).
Adverse Event Reporting Description	Safety data obtained during study visits associated with Study Days 1, 2, 3, 7, 10, 14, 21, and 28 were systematically assessed throughout the study. In addition, data from spontaneously reported AEs were included in safety assessments.
Arm/Group Title	Reltecimod 0.5 mg/kg		Placebo
Arm/Group Description	Single IV infusion of 0.5 mg/kg Reltecimod (at a concentration of 1 mg/mL)		Single IV infusion of 0.5 mL/kg of 0.9% sodium chloride (volume equivalent with Reltecimod dosing schema)
All Cause Mortality
	Reltecimod 0.5 mg/kg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/28 (17.9%)		6/30 (20%)
Serious Adverse Events
	Reltecimod 0.5 mg/kg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/28 (42.9%)		13/30 (43.3%)
Blood and lymphatic system disorders
Anemia	0/28 (0%)	0	1/30 (3.3%)	1
Leukocytosis	0/28 (0%)	0	1/30 (3.3%)	1
Cardiac disorders
Atrial fibrillation	1/28 (3.6%)	1	0/30 (0%)	0
Atrial flutter	1/28 (3.6%)	1	0/30 (0%)	0
Gastrointestinal disorders
Intestinal ischemia	0/28 (0%)	0	1/30 (3.3%)	1
Intra-abdominal fluid collection	1/28 (3.6%)	1	0/30 (0%)	0
General disorders
Organ failure	0/28 (0%)	0	1/30 (3.3%)	1
Hepatobiliary disorders
Hepatic failure	0/28 (0%)	0	1/30 (3.3%)	1
Infections and infestations
Abdominal wall infection	0/28 (0%)	0	1/30 (3.3%)	1
Pneumonia	0/28 (0%)	0	1/30 (3.3%)	1
Pneumonia escherichia	1/28 (3.6%)	1	0/30 (0%)	0
Postoperative wound infection	1/28 (3.6%)	1	0/30 (0%)	0
Retroperitoneal abscess	0/28 (0%)	0	1/30 (3.3%)	1
Sepsis	2/28 (7.1%)	2	0/30 (0%)	0
Septic shock	2/28 (7.1%)	2	0/30 (0%)	0
Injury, poisoning and procedural complications
Chemical peritonitis	0/28 (0%)	0	1/30 (3.3%)	1
Gastrointestinal anastomotic complication	1/28 (3.6%)	1	1/30 (3.3%)	1
Gastrointestinal anastomotic leak	0/28 (0%)	0	1/30 (3.3%)	1
Urethral injury	1/28 (3.6%)	1	0/30 (0%)	0
Metabolism and nutrition disorders
Fluid overload	1/28 (3.6%)	1	0/30 (0%)	0
Hyperkalemia	0/28 (0%)	0	1/30 (3.3%)	1
Nervous system disorders
Cerebral infarction	0/28 (0%)	0	1/30 (3.3%)	2
Product Issues
Device occlusion	1/28 (3.6%)	1	0/30 (0%)	0
Renal and urinary disorders
Acute kidney injury	1/28 (3.6%)	1	0/30 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute pulmonary edema	0/28 (0%)	0	1/30 (3.3%)	1
Chronic obstructive pulmonary disease	1/28 (3.6%)	1	0/30 (0%)	0
Respiratory failure	2/28 (7.1%)	2	2/30 (6.7%)	2
Other (Not Including Serious) Adverse Events
	Reltecimod 0.5 mg/kg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/28 (25%)		8/30 (26.7%)
Blood and lymphatic system disorders
Thrombocytosis	0/28 (0%)	0	2/30 (6.7%)	2
Infections and infestations
Pneumonia	0/28 (0%)	0	3/30 (10%)	3
Sepsis	2/28 (7.1%)	2	0/30 (0%)	0
Septic shock	2/28 (7.1%)	2	0/30 (0%)	0
Metabolism and nutrition disorders
Fluid overload	2/28 (7.1%)	2	0/30 (0%)	0
Psychiatric disorders
Delirium	0/28 (0%)	0	2/30 (6.7%)	2
Respiratory, thoracic and mediastinal disorders
Pleural effusion	0/28 (0%)	0	2/30 (6.7%)	2
Respiratory failure	2/28 (7.1%)	2	2/30 (6.7%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.