Study of HDV Insulin Versus Insulin in Type 1 Diabetes Subjects (ISLE-1)

NCT02794155 | Completed Phase 2

• 1 other identifier: DP 01-2015-01
• Study Type: interventional
• Target: 157
• Locations: 1 country
• Sites: 21

Brief Summary

This will be a Phase 2b, multicenter, randomized, double blind, titration clinical study, evaluating the efficacy and safety in the HDV Insulin Lispro Group versus Insulin Lispro Group in patients with type 1 diabetes over a 26 week treatment period. The patients will be randomized using a centrally allocated randomization scheme to 1 of the 2 treatment arms in an overall 2:1 scheme (HDV Insulin Lispro: Insulin Lispro). Both arms will receive the randomized treatment in combination with glargine or detemir. Goal to demonstrate that the efficacy of HDV insulin lispro administered in combination with a basal insulin (HDV Insulin Lispro group) is non-inferior to insulin lispro in combination with a basal insulin (Insulin Lispro group), in effects on glycated hemoglobin (HbA1c) in patients with type 1 diabetes. If non-inferiority is demonstrated, confirm that HDV insulin lispro in combination with a basal insulin (HDV Insulin Lispro group) is superior to insulin lispro in combination with a basal insulin (Insulin Lispro group), in effects on HbA1c in patients with type 1 diabetes (≥ 0.4% decrease in HbA1c).

Conditions

Type 1 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Change in HbA1c

  Change in HbA1c from Week 0 to Week 13, from Week 0 to Week 26, and from Week 13 to Week 26

  26 weeks

Secondary Outcomes (6)

• Change in fasting blood glucose glucose levels

  26 weeks

• Hypoglycemia occurrences by category: Severe, Documented Symptomatic, and Asymptomatic Hypoglycemia

  26 weeks

• Number of Patients with Adverse Events

  26 weeks

• Change in total insulin usage

  26 weeks

• Change in Body Weight

  26 weeks

Study Arms (2)

Test Group

EXPERIMENTAL

HDV Insulin Lispro subcutaneous, pre-prandial dosing, 26 week treatment period

Drug: HDV Insulin Lispro

Control Group

ACTIVE COMPARATOR

Insulin Lispro subcutaneous, Pre-prandial dosing, 26 week treatment period

Drug: Insulin LISPRO

Interventions

HDV Insulin Lispro DRUG

HDV Insulin Lispro: \~1% of the Insulin Lispro is bound to HDV (Hepatocyte Directed Vesicle)

Also known as: HDV Humalog

Test Group

Insulin LISPRO DRUG

Insulin Lispro: no bound insulin

Also known as: Humalog

Control Group

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women ≥ 18 yrs. of age
• Clinical diagnosis of Type 1 diabetes mellitus for at least 12 months
• Body Mass Index (BMI) ≤ 35 Kg/m2
• Basal insulin includes insulin Glargine or insulin Detemir
• Patient should be using bolus insulin defined as 2 to 4 doses of regular human insulin or rapid-acting analog at meals
• HbA1c ≥ 7.0% and ≤ 10.5%
• Fasting C-peptide ≤ 0.5 pmol/mL
• Willingness to adhere to protocol and perform all required tests
• Willing and able to review and sign the Informed Consent Form.
• If child bearing age, must use acceptable form of birth control (ligation, 2 forms of birth control)
• Willing to wear CGM devices and complete diaries.

You may not qualify if:

• Total daily insulin dose ≥ 1.5 IU/kg/day.
• History of recent blood transfusions (within previous 3 months), hemoglobinopathies, or any other conditions that effect HbA1c measurements
• Evidence of serious complications of diabetes (eg, Symptomatic autonomic neuropathy)
• Patients who are selected to but are unwilling or unable to participate in the MRI evaluation subset. (These patients may still participate in the non-MRI subset).
• Significant cardiovascular dysfunction or history within 12 months of Screening, eg, congestive heart failure (New York Heart Association Class III or IV), or clinically significant arrhythmia, myocardial infarction, cardiac surgery; history of valvular heart disease including mild or greater aortic insufficiency, or moderate or greater mitral insufficiency; recurrent syncope, transient ischemic attacks, or cerebrovascular accident
• Impaired liver function with elevated enzymes \> 50% above the normal range at Screening. Patients with elevated liver enzymes may have the test repeated only at Visit 2 on a case-by-case basis at the request of the PI.
• Creatinine level \> 2 mg/dL for men, and \> 1.8 mg/dL for women at Screening.
• Patient on low carbohydrate diet, such as Atkins Diet
• History of Adrenal supplementation within 3 years of Screening.
• History of unawareness or SEVERE recurrent hypoglycemia, defined as a patient who is unaware of symptoms of hypoglycemia, or due to autonomic dysfunction, has no inherent warnings of hypoglycemia, and therefore requires outside assistance to rectify any episodes of hypoglycemia
• Patients treated with systemic corticosteroids (Sporadic use of inhaled, intraarticular, and topical corticosteroids is not considered systemic).
• Patients with triglyceride levels ≥500 mg/dL at Screening.
• Patients with a history of cancer within the past 5 years, excluding basal or squamous cell carcinoma localized to the skin.
• Epilepsy or other physical or medical conditions which could result in non-compliance with the study.
• Participation in a clinical trial or use of an investigational drug within 30 days prior to admission to this study

Sponsors & Collaborators

• Diasome Pharmaceuticals: lead
• Integrium: collaborator

Study Sites (21)

Hope & Wellness Clinical Trials, Inc.

Corona, California, 92882, United States

Location

National Research Institute

Los Angeles, California, 90057, United States

Location

California Medical Research Associates Inc.

Northridge, California, 91324, United States

Location

Bay Area Clinical Research

San Carlos, California, 94070, United States

Location

Mills-Peninsula Health Services

San Mateo, California, 94401, United States

Location

Orange County Research Center

Tustin, California, 92780, United States

Location

Creekside Endocrine Associates, PC

Denver, Colorado, 80209, United States

Location

Advanced Pharma CR, LLC

Miami, Florida, 33147, United States

Location

Ormond Medical Arts Pharmaceutical Research Center

Ormond Beach, Florida, 32174, United States

Location

Progressive Medical Research

Port Orange, Florida, 32127, United States

Location

Atlanta Diabetes Associates

Atlanta, Georgia, 30318, United States

Location

Endocrine Research Solutions, Inc.

Roswell, Georgia, 30076, United States

Location

Rocky Mountain Diabetes & Osteoporosis Center, PA

Idaho Falls, Idaho, 83404, United States

Location

Associates in Endocrinology

Elgin, Illinois, 60124, United States

Location

University of Massachusetts Memorial Hospital

Worcester, Massachusetts, 01655, United States

Location

Desert Endocrinology Clinical Research Center

Henderson, Nevada, 89052, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

LION Research

Norman, Oklahoma, 73072, United States

Location

Endocrine and Psychiatry Center

Houston, Texas, 77095, United States

Location

Clinical Trials of Texas, Inc.

San Antonio, Texas, 78229, United States

Location

Rainier Clinical Research Center, Inc.

Renton, Washington, 98057, United States

Location

Related Publications (1)

• Klonoff D, Bode B, Cohen N, Penn M, Geho WB, Muchmore DB. Divergent Hypoglycemic Effects of Hepatic-Directed Prandial Insulin: A 6-Month Phase 2b Study in Type 1 Diabetes. Diabetes Care. 2019 Nov;42(11):2154-2157. doi: 10.2337/dc19-0152. Epub 2019 Sep 24.

  PMID: 31551249 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Insulin Lispro

Condition Hierarchy (Ancestors)

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

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 Officials

• David Klonoff, MD

  Mills-Peninsula Health Services

  PRINCIPAL INVESTIGATOR

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: May 16, 2016
• First Posted: June 8, 2016
• Study Start: June 1, 2016
• Primary Completion: April 28, 2018
• Study Completion: June 15, 2018
• Last Updated: July 31, 2018

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (21)