A Safety, Tolerability and Efficacy Study of Sernova's Cell Pouch™ for Clinical Islet Transplantation

• Sponsor: Sernova Corp
• Collaborators: CTI Clinical Trial and Consulting Services; Juvenile Diabetes Research Foundation; University of Chicago
• Information provided by (Responsible Party): Sernova Corp

Study Description

Brief Summary:

The Cell Pouch™ is a novel implantable device, that is transplanted with therapeutic cells such as insulin producing islets. This combination product is designed for the treatment of Type 1 Diabetes Mellitus (T1DM) with hypoglycemia unawareness and a history of severe hypoglycemic episodes. Upon implantation, the Cell Pouch™ is designed to form a natural environment, rich in tissue and microvessels for the transplant and function of therapeutic cells. The Cell Pouch™ is designed as a scaffold made of non-degradable polymers, formed into small cylindrical chambers which, when placed in the subcutaneous site, becomes incorporated with tissue and microvessels to the circumference of removable plugs within as early as two weeks as demonstrated in preclinical studies. After the tissue incorporation, the plugs are removed, leaving fully formed tissue chambers with central void spaces for the transplantation of therapeutic cells including Islets of Langerhans (islets). The Cell Pouch™ forms a natural environment, rich in microvessels that allows the transplanted islets to engraft with intravascular microvessels. It is believed this engraftment will enable long-term survival and function of transplanted islets. This study aims to demonstrate the safety and tolerability of islet transplantation into the Cell Pouch™ for the treatment of T1DM in subjects with hypoglycemia unawareness and a history of severe hypoglycemic episodes. The study also aims to establish islet release criteria that accurately characterize the islet product and are predictive of clinical transplant outcomes into the Cell Pouch™, which will be demonstrated through defined efficacy measures.

Condition or disease	Intervention/treatment	Phase
Type 1 Diabetes Mellitus	Combination Product: Sernova Cell Pouch™	Phase 1; Phase 2

Detailed Description:

The Sernova Cell Pouch™ will be implanted under the skin. A minimum of three weeks after Cell Pouch™ implantation, immunosuppression will be initiated and optimized for another 3 weeks. This will allow for proper vascularization of the Cell Pouch™ chambers and the patient to be stabilized on immunosuppression prior to transplantation. A mass, >3,000 islet equivalent (IEQ) numbers per kg of patient body weight (IEQ/kg), of highly purified islets will be transplanted in the Cell Pouch™. The Cell Pouch™ will be assessed for safety and tolerability for up to one year following transplant. Data for the primary and secondary endpoints will be summarized using descriptive statistics (such as counts and percentages).

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	7 participants
Intervention Model:	Single Group Assignment
Intervention Model Description:	Prospective, non-randomized, single arm
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Safety, Tolerability and Efficacy Study of Sernova's Cell Pouch™ for Clinical Islet Transplantation
Estimated Study Start Date :	July 2018
Estimated Primary Completion Date :	July 2019
Estimated Study Completion Date :	July 2021

Arms and Interventions

Arm

Intervention/treatment

Experimental: T1DM Cell Pouch™ Recipients; Eligible Type 1 Diabetes Mellitus (T1DM) subjects with hypoglycemia unawareness and a history of severe hypoglycemic episodes undergoing Sernova Cell Pouch™ intervention

Combination Product: Sernova Cell Pouch™; The Sernova Cell Pouch™ will be implanted under the skin. A minimum of three weeks after Cell Pouch™ implantation, immunosuppression will be initiated and optimized for another 3 weeks. This will allow for proper vascularization of the Cell Pouch™ chambers and the patient to be stabilized on immunosuppression prior to transplantation. A mass, >3,000 islet equivalent (IEQ) numbers per kg of patient body weight (IEQ/kg), of highly purified islets will be transplanted in the Cell Pouch™.

Outcome Measures

Primary Outcome Measures :

1. To assess the safety of the Cell Pouch™ following implantation, and islet transplantation, by evaluating the incidence and severity of adverse events (AEs) determined to be probable or highly probable to the Cell Pouch™ [ Time Frame: 365 days ±14 days ]
   Safety will be assessed by evaluating the incidence and severity of adverse events (AEs) determined to be probable or highly probable to the Cell Pouch™ following initial Cell Pouch™ implantation, at the time of islet transplantation, and following islet transplantation, and throughout the study up to 365 days ±14 days post-islet transplantation

Secondary Outcome Measures :

1. Survival of endocrine tissue in the Cell Pouch™ (defined by positive staining of islets during histological analysis) [ Time Frame: 90±5 days post-transplant for sentinel Cell Pouch™ ]
   Survival of endocrine tissue in the Cell Pouch™ (defined by positive staining of islets during histological analysis), as evaluated at day 90±5 days (post-removal of sentinel Mini Cell Pouch™); or post-removal of Cell Pouches™ at any time during the study
2. Proportion of participants with a reduction in severe hypoglycemic events [ Time Frame: From Day 0 to 90±5 ; Day 90±5 to Day 180±5; Day 180±5 to Day 365±14 following final Cell Pouch™ transplant and/or last transplant ]
   Number of participants with a reduction in severe hypoglycemic events following final Cell Pouch™ transplant and/or last islet transplant
3. Proportion of participants with a reduction in HbA1c >1mg% [ Time Frame: From Day 0 to 90±5 ; Day 90±5 to Day 180±5; Day 180±5 to Day 365±14 following final Cell Pouch™ transplant and/or last transplant ]
   Number of participants with a reduction in HbA1c >1mg% following final Cell Pouch™ transplant and/or last islet transplant

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 65 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

1. Male and female patients 18 to 65 years of age.
2. Ability to provide written informed consent.
3. Mentally stable and able to comply with the procedures of the study protocol.
4. Clinical history compatible with Type 1 Diabetes Mellitus (T1DM) with onset of disease at <40 years of age, insulin-dependence for ≥5 years at the time of enrollment, and a sum of patient age and insulin dependent diabetes duration of ≥28.
5. Absent stimulated c-peptide (<0.3 ng/mL) in response to a mixed meal tolerance test (MMTT; Boost® 6 mL/kg body weight to a maximum of 360 mL; another product with equivalent caloric and nutrient content may be substituted for Boost) measured during the 4 hour test.
6. Involvement in intensive diabetes management defined as self-monitoring of glucose values no less than a mean of three times each day averaged over each week and by the administration of three or more insulin injections each day or insulin pump therapy. Such management must be under the direction of an endocrinologist, diabetologist, or diabetes specialist with at least 3 clinical evaluations during the 12 months prior to study enrollment.
7. At least one episode of severe hypoglycemia in the 12 months prior to study enrollment.
8. Reduced awareness of hypoglycemia. More information about this criterion, including specific definitions of hypoglycemia unawareness, is in the protocol.

Exclusion Criteria:

1. Body mass index (BMI) >30 kg/m2
2. Insulin requirement >1.0 IU/kg/day
3. Glycated Haemoglobin (HbAlc) >11%.
4. Untreated proliferative diabetic retinopathy.
5. Blood Pressure: Systolic blood pressure (SBP) >160 mmHg or Diastolic Blood Pressure (DBP) >100 mmHg.
6. Measured glomerular filtration rate <70 mL/min/1.73m2 (More information about this criterion is in the protocol
7. Presence or history of macroalbuminuria (>300 mg/g creatinine).
8. Presence or history of panel-reactive anti-HLA antibodies >30%
9. For female subjects of child bearing potential: Positive pregnancy test, presently breast-feeding, or unwillingness to use effective contraceptive measures for the duration of the study and 4 months after discontinuation. For male subjects: intent to procreate during the duration of the study or within 4 months after discontinuation or unwillingness to use effective measures of contraception. More information about this criterion is in the protocol.
10. Presence or history of active infection including hepatitis B, hepatitis C, HIV, or tuberculosis (TB). Subjects with laboratory evidence of active infection are excluded even in the absence of clinical evidence of active infection.
11. Patients with negative screen for Epstein Barr Virus by Immunoglobulin G (IgG) determination. More information about this criterion is in the protocol,
12. Invasive aspergillus, histoplasmosis, or coccidioidomycosis infection within one year prior to study enrollment.
13. Any history of malignancy except for completely resected squamous or basal cell carcinoma of the skin.
14. Known active alcohol or substance abuse.
15. Baseline Hb below the lower limits of normal at the local laboratory for patients initially being enrolled into study.

16. Severe co-existing cardiac disease, characterized by any one of these conditions:

    • Recent myocardial infarction (within past 6 months).
    • Left ventricular ejection fraction <30%.
    • Uncontrolled coronary artery disease.
    • Known hypercoagulative state or
    • International Normalized Ratio > 1.8
17. Uncontrolled hyperlipidemia (fasting LDL cholesterol >130mg/dL and/or fasting triglycerides >200mg/dL) at the time of enrollment.
18. Persistent elevation of liver function tests at the time of enrollment. More information on this criterion is in the protocol
19. Severe unremitting diarrhea, vomiting or other gastrointestinal disorders potentially interfering with the ability to absorb oral medications (for example untreated celiac disease).
20. Untreated Graves' disease
21. Portal hypertension
22. Receiving treatment at the time of enrollment for a medical condition requiring chronic use of systemic steroids, except for the use of ≤ 5 mg prednisone daily, or an equivalent dose of hydrocortisone, for physiological replacement only.
23. Treatment with any anti-diabetic medication other than insulin within 4 weeks of transplant, More information on this criterion is in the protocol
24. Use of any investigational agents within 4 weeks of enrollment.
25. Administration of live attenuated vaccine(s) within 2 months of enrollment.
26. Any medical condition that, in the opinion of the study investigator, will interfere with safe participation in the trial.
27. Treatment with any immunosuppressive regimen at the time of enrollment.
28. A previous islet transplant.
29. A previous pancreas transplant. More information on this criterion is in the protocol
30. Known allergy or hypersensitivity to polymers More information on this criterion is in the protocol
31. Presence of colostomy/ileostomy, incisional hernia or other deformity of the abdominal wall precluding implantation of the Cell Pouch ™.
32. History of malignant hypertension or other conditions precluding general anesthesia. Use of coumadin or other anticoagulant therapy (except aspirin) or subject with prothrombin time (PT-INR) > 1.5.

Contacts and Locations

Locations

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United States, Illinois
University of Chicago Medical Center	Recruiting
Chicago, Illinois, United States, 60637
Contact: Lindsay Basto, RN, MSN 773-702-2504 Lindsay.basto@uchospitals.edu
Contact: Piotr Witkowski, MD, PhD 773 702-2447 pwitkowski@surgery.bsd.uchicago.edu
Principal Investigator: Piotr Witkowski, MD, PhD

Sponsors and Collaborators

Sernova Corp

CTI Clinical Trial and Consulting Services

Juvenile Diabetes Research Foundation

University of Chicago

More Information

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Responsible Party:	Sernova Corp
ClinicalTrials.gov Identifier:	NCT03513939 History of Changes
Other Study ID Numbers:	PROSVA201701
First Posted:	May 2, 2018
Last Update Posted:	July 6, 2018
Last Verified:	July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

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Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Keywords provided by Sernova Corp:

Type 1 Diabetes Mellitus, Diabetes, hypoglycemia

Additional relevant MeSH terms:

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Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose Metabolism Disorders; Metabolic Diseases	Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases