Efficacy and Safety of Reparixin in Pancreatic Islet Auto-transplantation

NCT01967888 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: REP0112
• Study Type: interventional
• Target: 104
• Locations: 2 countries
• Sites: 9

Brief Summary

The study is a phase 2/3, multicenter, double-blind, parallel assignment study. It involves 100 adult recipients of an intra-hepatic pancreatic Islet Auto-Transplantation (IAT). The objective of this clinical trial is to assess whether reparixin leads to improved transplant outcome as measured by the proportion of insulin-independent patients following IAT. The safety of reparixin in the specific clinical setting will be also evaluated.

Conditions

Pancreatectomy for Chronic Pancreatitis

Keywords

Pancreatic islet auto-transplantation

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients Who Were Insulin Independent After Islet Autotransplantation (IAT) at Day 365±14 Days After Transplant.

  Insulin-independence is defined as freedom from the need to take exogenous insulin for 14 or more consecutive days, with adequate glycemic control, as defined by: * a glycated hemoglobin (HbA1c) level \<6.5%; * fingerstick fasting blood glucose not exceeding 126 mg/dL more than three times in the past week (based on a minimum of one daily measurement; * a 2 hour post-prandial blood glucose not exceeding 180 mg/dL more than four times in the past week (based on a minimum of one daily measurement); * a laboratory fasting glucose in the non-diabetic range (\<126 mg/dL).

  day 365±14 after the transplant

Secondary Outcomes (31)

• Area Under the Curve (AUC) for the Serum C-peptide Level at Day 75±14 After the Transplant

  day 75±14 after the transplant

• Area Under the Curve (AUC) for the Serum C-peptide Level at Day 365±14 After the Transplant

  day 365±14 after the transplant

• Average Daily Insulin Requirements at Day 75±14 After the Transplant

  day 75±14 after the transplant

• Average Daily Insulin Requirements at Day 365±14 After the Transplant

  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

  day 75±14 after the transplant

Study Arms (2)

Reparixin

EXPERIMENTAL

Solution for intravenous (IV) infusion with active compound

Drug: Reparixin

Placebo

PLACEBO COMPARATOR

Physiologic solution

Drug: Placebo

Interventions

Reparixin DRUG

Solution for intravenous (IV) infusion; 2.772 mg/kg body weight/hour administered at 0.25 mL/kg/hour

Also known as: DF1681Y

Reparixin

Placebo DRUG

Physiologic solution administered at 0.25 mL/kg/hour

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Dompé Farmaceutici S.p.A: lead

Study Sites (9)

University of California. Department of Surgery, Division of Transplantation

San Francisco, California, 94143, United States

Location

The University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Schulze Diabetes Institute University of Minnesota Medical School

Minneapolis, Minnesota, 55455, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

The University of Cincinnati Medical Center

Cincinnati, Ohio, 45219, United States

Location

Thomas E. Starzl Transplantation Institute University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

University of Alberta, Clinical Islet Transplant Program

Edmonton, Alberta, T6G 2C8, Canada

Location

MeSH Terms

Interventions

reparixin

Limitations and Caveats

Non reported

Results Point of Contact

• Title: Mauro P. Ferrari, Pharm D
• Organization: Dompé

info@dompe.com

+3902583831

Study Officials

• Melena Bellin, MD

  Schulze Diabetes Institute; University of Minnesota Amplatz Children's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2013
• First Posted: October 23, 2013
• Study Start: February 1, 2014
• Primary Completion: January 1, 2018
• Study Completion: January 1, 2018
• Last Updated: November 2, 2023
• Results First Posted: October 9, 2019

Record last verified: 2023-10

Locations

CA (1); US (8)