A Phase 1/2a Clinical Trial to Evaluate the Efficacy and Safety of SCM-AGH in Patients With Moderate to Severe Acute Pancreatitis
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Pancreatitis, Acute
- Sponsor
- SCM Lifescience Co., LTD.
- Enrollment
- 36
- Locations
- 7
- Primary Endpoint
- The change from baseline in modified Marshall score on Day 7 for organ failure subject
- Status
- Completed
- Last Updated
- 2 years ago
Overview
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.
Investigators
Eligibility Criteria
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
- •Typical abdominal pain indicating acute pancreatitis
- •Increased blood level of pancreatic enzyme (amylase or lipase \>= three times of upper limit of normal)
- •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
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)
Outcomes
Primary Outcomes
The change from baseline in modified Marshall score on Day 7 for organ failure subject
Time Frame: Day 7
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
Time Frame: Day 28 for CTSI Subject
CTSI is scoring system to define the severity of acute pancreatitis. (4-6: Moderate, 7-10: Severe)
Secondary Outcomes
- Time to resolution of organ failure(Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 14, Day 21, Day 28)
- The change from baseline value of C-Reactive Protein(CRP) which is inflammatory marker on Day 1, 2, 3, 5, 7, and 14(Day 1, Day 2, Day 3, Day 5, Day 7, Day 14)
- Rate of infection(Day 28 or the day of discharge)
- Percentage of subjects whose organ failure was resolved at 3 days, 7 days, 14 days and 28 days(Day 3, Day 7, Day 14 and Day 28 or the day of discharge)
- The change from baseline in modified Marshall score at each assessment point up to Day 28(Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 14, Day 21, Day 28)
- 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(Day 1, Day 2, Day 3, Day 5, Day 7, Day 14)
- Duration of Systemic inflammatory response syndrome (SIRS)(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)
- The change from baseline in sequential organ failure assessment (SOFA) at each assessment point up to Day 28(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)
- Duration of intensive care unit (ICU) stay(Day 28 or the day of discharge)
- The change from baseline in Computed Tomography Severity Index(CTSI) on Day 28(Day 28 or the day of discharge)
- Requirement of drainage or surgery(Day 28 or the day of discharge)
- Incidence of pancreatic complication(Day 28 or the day of discharge)
- Mortality on Day 28 and 90(Day 28 or the day of discharge and Day 90)