Efficacy and Safety of Reparixin in Pancreatic Islet Auto-transplantation

• Register: ClinicalTrials.gov
• Last refreshed on: 13 November 2023
• Main ID: NCT01967888
• Date of registration: 18/10/2013
• Prospective Registration: Yes
• Primary sponsor: Dompé Farmaceutici S.p.A
• Public title: Efficacy and Safety of Reparixin in Pancreatic Islet Auto-transplantation
• Scientific title: A Phase 2/3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Assignment Study to Assess the Efficacy and Safety of Reparixin in Pancreatic Islet Auto-transplantation
• Date of first enrolment: February 2014
• Target sample size: 104
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT01967888
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 2/Phase 3

Countries of recruitment

Canada, United States

Contacts

• Name: Melena Bellin, MD
• Affiliation: Schulze Diabetes Institute; University of Minnesota Amplatz Children's Hospital

Key inclusion & exclusion criteria

Inclusion Criteria:

- Patients eligible for an IAT following total (or completion) pancreatectomy.

- Ages > 18 years.

- Patients willing and able to comply with the protocol procedures for the duration of
the study, including scheduled follow-up visits and examinations.

- Patients who have given written informed consent, prior to any study-related procedure
not part of normal medical care, with the understanding that consent may be withdrawn
by the patient at any time without prejudice to their future medical care.

Exclusion Criteria:

- Recipients of a previous IAT (if completion pancreatectomy).

- Patients undergoing total pancreatectomy due to either pancreatic cancer or pancreatic
benign diseases other than chronic pancreatitis, including insulinomas, etc.

- Patients with inadequate renal reserve as per calculated creatinine clearance (CLcr) <
60 mL/min according to the Cockcroft-Gault formula (1976).

- Patients with hepatic dysfunction as defined by increased ALT/AST > 3 x upper limit of
normal (ULN) or increased total bilirubin above the upper limit at local laboratory).
Patients with Gilbert's syndrome (elevated unconjugated bilirubin levels in the
absence of any evidence of hepatic or biliary tract disease) are not excluded.

- Patients with a preoperative International Normalized Ratio (INR) > 1.5 or any known
coagulopathy.

- Hypersensitivity to:

1. ibuprofen or to more than one non steroidal anti-inflammatory drug (NSAID).

2. medications belonging to the class of sulfonamides, such as sulfamethazine,
sulfamethoxazole, sulfasalazine, nimesulide or celecoxib.

- Concurrent sepsis (as per positive blood culture(s) and/or fever associated with other
signs of systemic sepsis syndrome).

- Treatment with systemic steroids in the 2 weeks prior to enrolment (except for the use
of <5mg prednisone daily or equivalent dose of hydrocortisone, for physiological
replacement only) or with any immune modulators in the 4 weeks prior to enrolment.

- Patients with pre-existing diabetes or evidence of impaired ß-cells function, based on
pre-operative fasting blood glucose >115 mg/dL and/or a HbA1c > 6.5%, or requiring
treatment with any anti-diabetic medication (e.g. insulin, metformin, etc) within the
2 weeks prior to enrolment.

- Use of any investigational agent in the 4 weeks prior to enrolment, including any
anti-cytokine/chemokine agents.

- Pregnant or breast-feeding women; unwillingness to use effective contraceptive
measures (females and males). (NB: pregnancy should be avoided in patients or partners
during the first month after completing the treatment with the Investigational
Product; no other specific warnings are described, considering the treatment course of
the Investigational Product, its PK profile, and the lack of significant adverse
effects on mating performance and fertility in animal studies).

- Patients with past or current history of alcohol abuse based on clinical history
and/or past treatment for alcohol addiction.

- Patients with evidence of pre-operative portal hypertension as per clinical history
and abdominal/liver imaging by ultrasound techniques.

Sites will comply with any additional or more restrictive exclusion criteria locally
accepted, as per centre practice.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Pancreatectomy for Chronic Pancreatitis

Intervention(s)

Drug: Reparixin

Drug: Placebo

Primary Outcome(s)

Percentage of Patients Who Were Insulin Independent After Islet Autotransplantation (IAT) at Day 365±14 Days After Transplant. [Time Frame: day 365±14 after the transplant]

Secondary Outcome(s)

Time Course From Basal to 240 Min of C-peptide Derived From the Mixed Meal Tolerance Test (MMTT) at Day 365±14 After the Transplant [Time Frame: day 365±14 after the transplant]

Time Course From Basal to 240 Min of Glucose Derived From the Mixed Meal Tolerance Test (MMTT) at Day 75±14 After the Transplant [Time Frame: day 75±14 after the transplant]

Cumulative Number of Episodes of Documented Asymptomatic Hypoglycemia From Day 75±14 to Day 365±14 After the Transplant [Time Frame: from day 75±14 to day 365±14 after the transplant]

Number of Serious Treatment Emergent Adverse Events Related to Investigational Product [Time Frame: Throughout the study From Day -1 to hospital discharge for all adverse events, and from then to day 365 post-transplantation only for serious adverse events]

Number of Treatment Emergent Adverse Events Related to Investigational Product [Time Frame: Throughout the study From Day -1 to hospital discharge]

Proportion of Patients by Steatorrhea Severity at Day 365±14 After the Transplant [Time Frame: day 365±14 after the transplant]

Peak C-peptide at Day 365 After the Transplant [Time Frame: Day 365±14 after the transplant]

Proportion of Patients by Steatorrhea Severity at Day 75±14 After the Transplant [Time Frame: day 75±14 after the transplant]

Proportion of Patients Falling Into One of the Following Malnutrition Risk Levels (Poor Prognosis, Significant Risk, Increased Risk, Normal) According to Pre-albumin Level at Day 75±14 After the Transplant [Time Frame: day 75±14 after the transplant]

Cumulative Number of Episodes of Documented Symptomatic Hypoglycemia From Day 75±14 to Day 365±14 After the Transplant [Time Frame: from day 75±14 to day 365±14 after the transplant]

Incidence and Severity of Adverse Events and Serious Adverse Events Throughout the Study [Time Frame: up to day 365±14 after the transplant]

Proportion of Patients Falling Into One of the Following Malnutrition Risk Levels (Poor Prognosis, Significant Risk, Increased Risk, Normal) According to Pre-albumin Level at Day 365±14 After the Transplant [Time Frame: day 365±14 after the transplant]

Proportion of Patients With an HbA1c <6.5% at Day 365±14 After the Transplant [Time Frame: day 365±14 after the transplant]

Area Under the Curve (AUC) for the Serum C-peptide Level at Day 365±14 After the Transplant [Time Frame: day 365±14 after the transplant]

Proportion of Patients With an HbA1c <6.5% at Day 365±14 After the Transplant AND Free of Severe Hypoglycemic Events From Day 75±14 to Day 365±14 After the Transplant Inclusive [Time Frame: from day 75±14 to day 365±14 after the transplant]

Average Daily Insulin Requirements at Day 365±14 After the Transplant [Time Frame: day 365±14 after the transplant]

Change From Baseline in Post-transplant Aspartate Aminotransferase (AST) [Time Frame: Baseline, Days 2, 3, 7, 75±14 after the transplant]

Cumulative Number of Diabetic Ketoacidosis-related Events [Time Frame: from day 75±14 to day 365±14 after the transplant]

Peak C-peptide at Day 75 After the Transplant [Time Frame: Day 75±14 after the transplant]

Time Course From Basal to 240 Min of Glucose Derived From the Mixed Meal Tolerance Test (MMTT) at Day 365±14 After the Transplant [Time Frame: day 365±14 after the transplant]

Time Course From Basal to 240 Min of Insulin Derived From the Mixed Meal Tolerance Test (MMTT) at Day 75±14 After the Transplant [Time Frame: day 75±14 after the transplant]

Area Under the Curve (AUC) for the Serum C-peptide Level at Day 75±14 After the Transplant [Time Frame: day 75±14 after the transplant]

Change From Baseline in Post-transplant Alanine Aminotransferase (ALT) [Time Frame: Baseline, Days 2, 3, 7, 75 ±14 after the transplant]

Cumulative Number of Severe Hypoglycemic Events From Day 75±14 to Day 365±14 After the Transplant [Time Frame: from day 75±14 to day 365±14 after the transplant]

Time Course From Basal to 240 Min of C-peptide Derived From the Mixed Meal Tolerance Test (MMTT) at Day 75±14 After the Transplant [Time Frame: day 75±14 after the transplant]

ß-cell Function at Day 365±14 After the Transplant [Time Frame: day 365±14 after the transplant]

Average Daily Insulin Requirements at Day 75±14 After the Transplant [Time Frame: day 75±14 after the transplant]

ß-cell Function at Day 75±14 After the Transplant [Time Frame: day 75±14 after the transplant]

Time Course From Basal to 240 Min of Insulin Derived From the Mixed Meal Tolerance Test (MMTT) at Day 365±14 After the Transplant [Time Frame: day 365±14 after the transplant]

Time-to-peak C-peptide at Day 75 After the Transplant [Time Frame: day 75±14 and day 365±14 after the transplant]

Time-to-peak C-peptide at Day 365 After the Transplant [Time Frame: Day 365±14 after the transplant]

Secondary ID(s)

REP0112

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 09/10/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01967888