Pilot Study Evaluating Safety of ExOlin® in Patients With Poorly Controlled Type 1 Diabetes

NCT05221359 | Recruiting DMC

• 3 other identifiers: DEXN-T1D-2017-012020-A01763-362020-003020-17
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

First in Human, pilot investigation An Open Label, Monocentric, Pilot Study Evaluating Safety of ExOlin® in Patients with Poorly Controlled Type 1 Diabetes with High Glucose Fluctuations, Prone to Severe Hypoglycemia

Conditions

Type 1 Diabetes; Type 1 Diabetes Mellitus With Hypoglycemia

Keywords

Safety; Pilot; Type 1 Diabetes; High glucose fluctuations; Severe Hypoglycemia; Hypoglycemia unawareness; Extraperitoneal; Insulin

Outcome Measures

Primary Outcomes (2)

• Safety: Percentage of patients who will experience at least one relevant adverse event (AE) judged by the investigator as probably or highly probably related to ExOlin® for the duration of mandatory phases of the study

  Percentage of patients who will experience at least one relevant adverse event (AE) judged by the investigator as probably or highly probably related to ExOlin® for the duration of the study : * Linked to implantation (any unexpected or severe signs of cutaneous or extraperitoneal intolerance s.a. redness, edema or delayed healing, as per clinical exam of the skin and palpation in regard of the scar and SC port, associated to systemic signs s.a. fever, chills, abnormal biologic values \[including: complete blood count, C-reactive protein\]); * linked to therapeutic use of ExOlin (i.e. to administrate insulin: ExOlin® device failure or local infection); * other unexpected related AEs. The primary endpoint will be achieved when the device has been retrieved from all enrolled patients and post-explantation observation time (3 months post explantation) has been completed.

  From implantation of the device (4 weeks after screening visit) till end of post-explantation safety follow-up (week 36), meaning a duration of 32 weeks.

• Safety: Percentage of patients who will experience at least one relevant adverse event (AE) judged by the investigator as probably or highly probably related to ExOlin® for the whole duration of the study (extension phase included)

  Percentage of patients who will experience at least one relevant adverse event (AE) judged by the investigator as probably or highly probably related to ExOlin® for the duration of the study : * Linked to implantation (any unexpected or severe signs of cutaneous or extraperitoneal intolerance s.a. redness, edema or delayed healing, as per clinical exam of the skin and palpation in regard of the scar and SC port, associated to systemic signs s.a. fever, chills, abnormal biologic values \[including: complete blood count, C-reactive protein\]); * linked to therapeutic use of ExOlin (i.e. to administrate insulin: ExOlin® device failure or local infection); * other unexpected related AEs. The primary endpoint will be achieved when the device has been retrieved from all enrolled patients and post-explantation observation time (3 months post explantation) has been completed.

  From implantation of the device (4 weeks after screening visit) till end of post-explantation safety follow-up, meaning a duration up to of 168 weeks maximum for patients completing extension phase.

Secondary Outcomes (7)

• Safety : Percentage of patients who will experience at least one AE, according to its severity, seriousness, relation with the device or the surgery or the treatment, outcome, by system-organ-class and preferred term.

  From implantation of the device through study completion, meaning from 1 month after screening, duration of 8 months for mandatory phases and up to 3 years and 3 months for patients reaching end of extension phase

• Safety: Percentage of participants with abnormal vital signs or physical findings.

  From implantation of the device through study completion, meaning from 1 month after screening, duration of 8 months for mandatory phases and up to 3 years and 3 months for patients reaching end of extension phase

• Early Performance: Glycemic control

  2nd month of treatment (meaning week 20) vs end of screening (week 4)

• Early Performance: Glycemic control

  3rd month of treatment (meaning week 24) vs end of screening (week 4)

• Early Performance: Glycemic control

  Every 4 weeks starting from 2nd month of treatment (meaning week 20) and till end of use of ExOlin (up to week 160) vs end of screening (week 4)

Study Arms (1)

test arm

EXPERIMENTAL

All patients will be enrolled in same arm which contains the two interventions (device + drug) and follow mandatory phases of trial: screening, implantation, treatment with ExOlin, explantation.

Device: ExOlin®; Drug: Insulin aspart

Interventions

ExOlin® DEVICE

Implantation of ExOlin® device, safety follow-up followed by a treatment period in which device is used to administer insulin. Device explanted with a safety follow-up.

test arm

Insulin aspart DRUG

Use of NovoRapid insulin during all periods of the clinical investigations

test arm

Eligibility Criteria

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

You may qualify if:

• Adult men or women (age ≥ 18 years);
• Diagnosis of Type 1 Diabetes (T1D) for more than 2 years at the start of screening;
• Body mass index (BMI) \> 16 kg/m2 and \< 35 kg/m2;
• Well managed intensive SubCutaneous (SC) insulin therapy, i.e. patient using for at least 3 months:
• CSII, whatever the insulin pump used, and
• Continuous Glucose Monitoring (CGM), by using Dexcom G6;
• % \< Serum HbA1c \< 12.0%;
• Patient characterized by one of the following conditions:
• Unstable diabetes/poor glycemic control, meaning patient presenting:
• at least one episode of severe hypoglycemia during the 12 months prior to study screening. Severe hypoglycemia is defined by American Diabetes Association (ADA) standards as "severe cognitive impairment requiring assistance from another person for recovery" (as per ADA's definition in "standards of care in diabetes");
• or glycemic excursions (post-prandial hyperglycemic or nocturnal hypoglycemic episodes) considered as too frequent and of high amplitude by the investigator, during the previous month;
• Presence of adverse side effects of SC insulin-therapy:
• SC insulin resistance;
• or severe acquired lipodystrophy resistant to pump treatment;
• or genetic skin atrophy or lipodystrophy.

You may not qualify if:

• Renal glomerular filtration rate \<30 mL/min/1.73m2 as per Chronic Kidney Disease - Epidemiology Collaboration (CDK-EPI) calculation;
• Immunocompromised patient;
• Local or systemic acute or chronic inflammation (rheumatoid arthritis, sclerodermia);
• Active infection or inflammation;
• Known history of skin affliction that could impact ExOlin® tolerance;
• Ongoing active anticoagulant therapy;
• Severe wound healing issues;
• Parietal reinforcement prostheses;
• Known allergy to one of the devices' components, including known allergy to fixation systems (e.g. patch, plaster) for SC administration devices such as external pumps and CGM, or chronic allergy related to prolonged wearing of such systems;
• Known allergy to insulin NovoRapid®;
• Known allergy to anesthetics, or products containing iodine and its derivates, or antibiotics used during surgery (cefazolin, and combination of clindamycin and gentamycin);
• Activity contraindicated as per external pump and CGM use recommendations;
• Patient willing to practice activities with risks of trauma or major change in the environment pressure such as combat sport or scuba diving;
• Cardiac condition incompatible with surgery requirements as per anesthesiologist's opinion;
• Unstable diabetic retinopathy (as per ophthalmologist's review within 6 months before screening);

Sponsors & Collaborators

• Defymed: lead

Study Sites (1)

Hôpitaux Universitaires de Strasbourg

Strasbourg, 67000, France

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Hypoglycemia; Insulin Resistance

Interventions

Insulin Aspart

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Insulin, Short-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: All patients enrolled will undergo period with subcutaneous delivery of insulin, as a baseline data collection. Then, patients will receive the ExOlin device, undergo post-implantation FU, and then get insulin therapy via ExOlin. Explantation of the device, when required, will be accompanied by a safety FU. During all study phases, NovoRapid insulin will be used.

Study Record Dates

• First Submitted: December 3, 2021
• First Posted: February 3, 2022
• Study Start: May 5, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): April 1, 2027
• Last Updated: July 27, 2022

Record last verified: 2022-07

Locations

FR (1)