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Safety and Efficacy of SCM-AGH in Patients With Moderate to Severe Acute Pancreatitis

Primary Purpose

Pancreatitis, Acute

Status

Completed

Phase

Phase 1

Locations

Korea, Republic of

Study Type

Interventional

Intervention

SCM-AGH

Placebo

About this trial

This is an interventional treatment trial for Pancreatitis, Acute

Eligibility Criteria

19 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

>=19 years of age
[Phase I]
Patient with acute pancreatitis with organ failure which has been determined as severe acute pancreatitis prior to assignment(randomization) (1) Organ failure: 2 points of Modified Marshall Score in one or more of the respiratory system, renal system and cardiovascular system (2) Acute pancreatitis: at least 2 of the following 3 conditions are met
1. Typical abdominal pain indicating acute pancreatitis
2. Increased blood level of pancreatic enzyme (amylase or lipase >= three times of upper limit of normal)
3. Finding acute pancreatitis in imaging test (contrast enhanced computerized tomography, abdominal magnetic resonance imaging, or abdominal sonography) (3) Severe: at least 1 of following organ failures lasting for > 48 hours according to the 2012 Atlanta Classification
  - Respiratory system: PaO2/FiO2 =< 300
  - Renal system: Creatinine >= 1.9 mg/dL
  - Cardiovascular system: low systolic blood pressure persists despite fluid replacement (SBP < 90 mmHg. off inotropic support)
Patient who or whose representative voluntarily agrees to participate in this study and has given a written informed consent

[Phase II] 2) Patient with acute pancreatitis with organ failure or CTSI score >= 4 which has been determined as moderate to severe acute pancreatitis prior to assignment(randomization)

Organ failure: 2 points of Modified Marshall Score in one or more of the respiratory system, renal system and cardiovascular system
CTSI: Sum of Balthazar grade and Necrosis score. CTSI 1-3: Mild / CTSI 4-6: Moderate / CTSI 7-10: Severe
Acute pancreatitis: at least 2 of the following 3 conditions are met
a.Typical abdominal pain indicating acute pancreatitis b. Increased blood level of pancreatic enzyme (amylase or lipase >= three times of upper limit of normal) c. Finding acute pancreatitis in imaging test (contrast enhanced computerized tomography, abdominal magnetic resonance imaging, or abdominal sonography)
Moderate to Severe at least 1 of following organ failures lasting according to the 2012 Atlanta Classification - Respiratory system: PaO2/FiO2 =< 300 - Renal system: Creatinine >= 1.9 mg/dL
- Cardiovascular system: low systolic blood pressure persists despite fluid replacement (SBP < 90 mmHg. off inotropic support)

[Moderately Severe]

organ failures lasting for < 48 hours according to the 2012 Atlanta Classification or CTSI 4-8,

[Severe]

organ failures lasting for >= 48 hours according to the 2012 Atlanta Classification
3) Patient who or whose representative voluntarily agrees to participate in this study and has given a written informed consent

Exclusion Criteria:

Patient with allergic or hypersensitivity reaction to investigational product, drug of similar class or ingredients (bovine serum, dimethyl sulfoxide)
Patient who cannot undergo contrast-enhanced computerized tomography due to allergic reaction to contrast medium
Patient past >72 hours after the onset of organ failure at assignment (randomization)
Patient with condition that may develop acute abdominal pain
Patient with pancreatitis resulting from trauma, surgery, or neoplasm
Patient with unstable ventilation due to underlying disease other than pancreatitis
Patient with active infection such as non-pancreatic infection, septicemia, or pneumonia resulting from other disease
Patient requiring urgent surgery within 7 days
Patient with severe comorbidity (chronic renal disease, hepatic cirrhosis, chronic obstructive lung disease, bronchial asthma, congestive heart failure)
Patient with evidence of chronic pancreatitis (recurrent, obstructive and chronic; autoimmune and chronic; marked pancreatic insufficiency such as steatorrhea)
Pregnant woman, breastfeeding woman, or woman and man of reproductive potential not willing to use contraceptive measures during the study period
Patient who received other investigational product/device within 30 days prior to screening
Patient not eligible for study participation in the opinion of the investigator
Patient with current or past malignancy

Sites / Locations

Soonchunhyang University Hosptial Bucheon
Kyungpook National University Chilgok Hospital
Dongguk University Ilsan Hospital
Chonnam National University Medical School
Inha University Hospital
Ajou University Hospital
Wonju Severance Christian Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

SCM-AGH

Placebo

Arm Description

Ingredient: Allogeneic human bone marrow derived mesenchymal stem cells Dose: 1x10^6 cells/Kg

IV infusion.

Outcomes

Primary Outcome Measures

The change from baseline in modified Marshall score on Day 7 for organ failure subject

The modified Marshall score is the scoring system to define the organ failure. The score is based on three different scores, one each for the respiratory, cardiovascular and renal. the modified Marshall score is >2 through the respiratory, renal or cardiovascular system, it is called organ failure.

The change from baseline in CTSI Score on Day 28

CTSI is scoring system to define the severity of acute pancreatitis. (4-6: Moderate, 7-10: Severe)

Secondary Outcome Measures

Percentage of subjects whose organ failure was resolved at 3 days, 7 days, 14 days and 28 days

The change from baseline in modified Marshall score at each assessment point up to Day 28

The change from baseline in sequential organ failure assessment (SOFA) at each assessment point up to Day 28

SOFA score is used to track a person's status during the stay in an intensive care unit (ICU) to determine the extent of a person's organ function or rate of failure. The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems.

Duration of Systemic inflammatory response syndrome (SIRS)

Time to resolution of organ failure

The modified marshall score is 0 or 1 for all organ in respiratory, cardiovascular and renal.

The change from baseline value of C-Reactive Protein(CRP) which is inflammatory marker on Day 1, 2, 3, 5, 7, and 14

Change from baseline in inflammatory markers(change of Tumor Necrosis Factor(TNF)-α, interleukin(IL)-6, TGF-b1, CCL2 and Lymphocyte count ratio) on Day 1, 2, 3, 5, 7, and 14

Duration of intensive care unit (ICU) stay

Number of days for stay duration at ICU. The duration is from the day of hospitalization to day of discharge.

The change from baseline in Computed Tomography Severity Index(CTSI) on Day 28

CTSI is the sum of Balthazar grade and necrosis score. The scoring is defined by evaluation of abdominal Computed Tomography(CT).

Incidence of pancreatic complication

Pancreatic complication will be evaluated by abdominal CT.

Requirement of drainage or surgery

Requirement of drainage due to intra-abdominal catastrophe or necrosis and surgery due to hemorrhage, perforation or abdominal compartment syndrome will be evaluated until Day 28.

Rate of infection

The even of infection such as infected pancreatic necrosis, bacteremia and pneumonia. The several tests for diagnosis can be conducted per investigator's decision.

Mortality on Day 28 and 90

Full Information

NCT ID

NCT04189419

First Posted

December 4, 2019

Last Updated

June 7, 2023

Sponsor

SCM Lifescience Co., LTD.

1. Study Identification

Unique Protocol Identification Number

NCT04189419

Brief Title

Safety and Efficacy of SCM-AGH in Patients With Moderate to Severe Acute Pancreatitis

Official Title

A Phase 1/2a Clinical Trial to Evaluate the Efficacy and Safety of SCM-AGH in Patients With Moderate to Severe Acute Pancreatitis

Study Type

Interventional

2. Study Status

Record Verification Date

May 2022

Overall Recruitment Status

Completed

Study Start Date

August 12, 2019 (Actual)

Primary Completion Date

January 14, 2022 (Actual)

Study Completion Date

March 15, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

SCM Lifescience Co., LTD.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

This study consists of two phases (Phase I and Phase IIa). Phase IIa will be conducted sequentially after the safety of SCM-AGH is secured in Phase I. Phase I: Multicenter in Korea, Non-Randomized, Open-label, Single Arm, 3+3 design) for Severe Acute Pancreatitis Phase II: Multicenter in Korea, Randomized, Double-blind, 2-arm, Placebo-controlled, Parallel arm for Moderate to Severe Acute Pancreatitis

Detailed Description

Phase I (Multicenter in Korea, Non-Randomized, Open-label, Single Arm, 3+3 design): Three and up to six patients with severe Acute Pancreatitis are planned to recruit from 12 sites in Korea, but additional three patients can be enrolled by an assessment of Adverse Drug Reaction(ADR) from first three subjects . Subjects will be administered with SCM-AGH as an intravenous (IV) infusion once a day for 3 days. Efficacy and safety are assessed daily for the first week, and then weekly on 3 occasions (Day 14, 21, and 28). Survival is followed up until Day 90. Phase II (Multicenter in Korea, Randomized, Double-blind, 2-arm, Placebo-controlled, Parallel arm): Eligible patients will be randomized to the SCM-AGH group or placebo group at 1:1 ratio. Total 36 patients with Moderate to Severe Acute Pancreatitis are planned to be enrolled from 12 sites in Korea. Subjects will receive SCM-AGH on Day 0, 1, and 2. Existing standard of care is permitted. Efficacy and safety are assessed daily for the first week, and then weekly on 3 occasions (Day 14, 21, and 28). Survival is followed up until Day 90.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pancreatitis, Acute

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Model Description

Phase I: Multicenter in Korea, Non-Randomized, Open-label, Single arm, 3+3 design Phase II: Multicenter in Korea, Randomized, Double-blind, Placebo-controlled, 2-arm, Parallel Group

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

36 (Actual)

8. Arms, Groups, and Interventions

Arm Title

SCM-AGH

Arm Type

Experimental

Arm Description

Ingredient: Allogeneic human bone marrow derived mesenchymal stem cells Dose: 1x10^6 cells/Kg

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

IV infusion.

Intervention Type

Biological

Intervention Name(s)

SCM-AGH

Intervention Description

SCM-AGH will be administrated once a day for 3 days(D0, D1 and D2).

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Placebo will be administrated once a day for 3 days(D0, D1 and D2).

Primary Outcome Measure Information:

Title

The change from baseline in modified Marshall score on Day 7 for organ failure subject

Description

Time Frame

Day 7

Title

The change from baseline in CTSI Score on Day 28

Description

CTSI is scoring system to define the severity of acute pancreatitis. (4-6: Moderate, 7-10: Severe)

Time Frame

Day 28 for CTSI Subject

Secondary Outcome Measure Information:

Title

Percentage of subjects whose organ failure was resolved at 3 days, 7 days, 14 days and 28 days

Time Frame

Day 3, Day 7, Day 14 and Day 28 or the day of discharge

Title

The change from baseline in modified Marshall score at each assessment point up to Day 28

Time Frame

Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 14, Day 21, Day 28

Title

The change from baseline in sequential organ failure assessment (SOFA) at each assessment point up to Day 28

Description

Time Frame

Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 14, Day 21, Day 28 or the day of discharge

Title

Duration of Systemic inflammatory response syndrome (SIRS)

Time Frame

Day 0, Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 14, Day 21, Day 28 or the day of discharge

Title

Time to resolution of organ failure

Description

The modified marshall score is 0 or 1 for all organ in respiratory, cardiovascular and renal.

Time Frame

Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 14, Day 21, Day 28

Title

The change from baseline value of C-Reactive Protein(CRP) which is inflammatory marker on Day 1, 2, 3, 5, 7, and 14

Time Frame

Day 1, Day 2, Day 3, Day 5, Day 7, Day 14

Title

Change from baseline in inflammatory markers(change of Tumor Necrosis Factor(TNF)-α, interleukin(IL)-6, TGF-b1, CCL2 and Lymphocyte count ratio) on Day 1, 2, 3, 5, 7, and 14

Time Frame

Day 1, Day 2, Day 3, Day 5, Day 7, Day 14

Title

Duration of intensive care unit (ICU) stay

Description

Number of days for stay duration at ICU. The duration is from the day of hospitalization to day of discharge.

Time Frame