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

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

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

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.

Inclusion Criteria:

1. >=19 years of age

   [Phase I]

2. 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)

3. 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)

1. Organ failure: 2 points of Modified Marshall Score in one or more of the respiratory system, renal system and cardiovascular system

2. CTSI: Sum of Balthazar grade and Necrosis score. CTSI 1-3: Mild / CTSI 4-6: Moderate / CTSI 7-10: Severe

3. 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)

4. 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:

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