INHALE-3: Afrezza® Combined With Insulin Degludec Versus Usual Care in Adults With Type 1 Diabetes

NCT ID: NCT05904743

Last Updated: 2024-08-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 141 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-07-07
• Study Completion Date: 2024-06-24

Brief Summary

INHALE-3 is a Phase 4, randomized controlled trial (RCT) that will randomly assign participants ≥18 years of age with type 1 diabetes (T1D) using multiple daily injections (MDI), an automated insulin delivery (AID) system, or a pump without automation, and continuous glucose monitoring (CGM) 1:1 to an insulin regimen of insulin degludec plus inhaled insulin (Afrezza) and CGM or continuation of usual care. The primary outcome of the RCT is at 17 weeks. The RCT will be followed by a 13-week extension phase in which participants in both groups will use the degludec-inhaled insulin regimen.

Conditions

Diabetes Mellitus, Type 1

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Afrezza (Technosphere Insulin) + insulin degludec

The Afrezza-Degludec group will inhale Afrezza at meals and corrections and will inject insulin degludec once a day for the 17 weeks of the RCT Phase. Dexcom Continuous Glucose Monitoring (CGM) will be provided. The Afrezza-Degludec group will continue to use Afrezza and insulin degludec for an additional 13 weeks in the Extension Phase.

Group Type: EXPERIMENTAL

Afrezza

Intervention Type: BIOLOGICAL

Pharmaceutical form: powder Route of administration: inhalation

insulin degludec

Intervention Type: BIOLOGICAL

Pharmaceutical form: solution for injection Route of administration: subcutaneous

Usual Care: Insulin delivery with either MDI, a pump without automation, or an AID system and CGM

The Usual Care group will continue to receive insulin as they did before the study. This could be by multiple daily injections (MDI) or by using an insulin pump with or without automation for the 17 weeks of the randomized controlled trial (RCT) Phase. Participants will continue to use their personal continuous glucose monitor (CGM) as they did before the study. The Usual Care group will then use Afrezza and insulin degludec for 13 weeks in the Extension Phase. Dexcom CGM will be provided during the Extension Phase.

Group Type: ACTIVE_COMPARATOR

Rapid-acting Insulin Analog

Intervention Type: BIOLOGICAL

Pharmaceutical form: clear and colorless solution for injection Route of administration: subcutaneous

Basal Insulin

Intervention Type: BIOLOGICAL

Pharmaceutical form: clear and colorless solution for injection Route of administration: subcutaneous

Interventions

Afrezza

Pharmaceutical form: powder Route of administration: inhalation

Intervention Type: BIOLOGICAL

insulin degludec

Pharmaceutical form: solution for injection Route of administration: subcutaneous

Intervention Type: BIOLOGICAL

Rapid-acting Insulin Analog

Pharmaceutical form: clear and colorless solution for injection Route of administration: subcutaneous

Intervention Type: BIOLOGICAL

Basal Insulin

Pharmaceutical form: clear and colorless solution for injection Route of administration: subcutaneous

Intervention Type: BIOLOGICAL

Other Intervention Names

Technosphere Insulin; any FDA approved Rapid-acting Insulin Analog; any FDA approved Basal Insulin

Eligibility Criteria

Inclusion Criteria

• Ability to provide informed consent for study participation
• Clinical diagnosis of T1D (per the Investigator)
• Treatment with insulin for at least 6 months prior to the collection of the baseline continuous glucose monitoring (CGM) data
• Same treatment regimen (MDI, an AID system, or an insulin pump without automation) for the 3 months prior to screening

1. Current (at time of screening) rapid-acting insulin analog (RAA) in use for at least 4 weeks

2. If AID system used, automated insulin delivery must be active >85% of the time in the 4 weeks prior to screening

3. If MDI used, participant must be using a long-acting basal insulin plus injecting a RAA bolus for meals, per Investigator

• Total daily insulin dose 20-100 units
• Age ≥ 18 years
• HbA1c <11.0%
• Participant uses real-time CGM (any type of real-time CGM) on a regular basis (at least 70% of the time in the 4 weeks prior to screening)
• No use of inhaled insulin in the 3 months prior to screening
• If female of childbearing potential, willing and able to have pregnancy testing
• Investigator believes that the participant can safely use the study treatment and will follow protocol
• No medical, psychiatric,or other conditions, or medications being taken that in the Investigator's judgement would be a safety concern for participation in the study

1. This includes considering the potential impact of medical conditions known to be present including cardiovascular, liver, kidney disease, thyroid disease, adrenal disease, malignancies, vision difficulties, active proliferative retinopathy, and other medical conditions; psychiatric conditions including eating disorders; drug or alcohol abuse.

Exclusion Criteria

• History of recent blood transfusions (within previous 3 months prior to randomization), hemoglobinopathies, (sickle cell trait is not an exclusion), or any other conditions that affect HbA1c measurements
• Recent history of asthma (defined as using any medications to treat within the last year), chronic obstructive pulmonary disease (COPD), or any other clinically important pulmonary disease (e.g., cystic fibrosis or bronchopulmonary dysplasia), or significant congenital or acquired cardiopulmonary disease as judged by the Investigator
• Exposure to any investigational product(s), including drugs or devices, in the 90 days prior to the start of screening
• Any disease other than diabetes or current use (or anticipated use during the study) of any medication that, in the judgment of the Investigator, may impact glucose metabolism
• Current or anticipated acute uses of oral, inhaled or injectable glucocorticoids during the time period of the trial (topical glucocorticoid use is acceptable)
• Use of a non-insulin glucose-lowering medication within 3 months prior to signing informed consent
• Smoking (includes cigarettes, cigars, pipes, marijuana, and vaping devices) within 3 months prior to screening
• Pregnant or lactating, planning to become pregnant during the study, or is a woman of childbearing potential and not on an acceptable form of birth control (acceptable includes abstinence, condoms, oral/injectable contraceptives, IUD, or implant); childbearing means that menstruation has started, and the participant is not surgically sterile or greater than 12 months post-menopausal
• No known stage 4/5 renal failure or on dialysis
• Taking Hydroxyurea medication
• An event of severe hypoglycemia, as judged by the Investigator, within the last 90 days prior to screening
• An episode of diabetic ketoacidosis (DKA) diagnosed at a health care facility within the 90 days prior to screening or severe hypoglycemia event within the 90 days prior to screening
• Employed by, or having immediate family members employed by MannKind Corporation or JAEB Center for Health Research, or having a direct supervisor at place of employment who is also directly involved in conducting the clinical trial (as Study Investigator, coordinator, etc.); or having a first-degree relative who is directly involved in in conducting the clinical trial
• Have a history or current diagnosis of lung cancer

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jaeb Center for Health Research

OTHER

Sponsor Role: collaborator

Mannkind Corporation

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kevin Kaiserman, MD

Role: STUDY_DIRECTOR

Mannkind Corporation

Irl B. Hirsch, MD

Role: STUDY_CHAIR

University of Washington

Locations

Loma Linda University-Diabetes Treatment Center

Loma Linda, California, United States

Sansum Diabetes Research

Santa Barbara, California, United States

Barbara Davis Center

Aurora, Colorado, United States

Atlanta Diabetes Associates

Atlanta, Georgia, United States

Northwestern University Division of Endocrinology, Metabolism and Molecular Medicine

Chicago, Illinois, United States

Iowa Diabetes Research

West Des Moines, Iowa, United States

Boston Medical Center

Boston, Massachusetts, United States

Joslin Diabetes Center

Boston, Massachusetts, United States

Mayo Clinic

Rochester, Minnesota, United States

Las Vegas Endocrinology

Henderson, Nevada, United States

Endocrine Associate of West Village, PC

Long Island City, New York, United States

Mount Sinai Diabetes Center

New York, New York, United States

SUNY Upstate Medical University

Syracuse, New York, United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Texas Diabetes & Endocrinology, P.A.

Austin, Texas, United States

The University of Texas Southwestern Medical Center

Dallas, Texas, United States

Diabetes and Glandular Disease Clinic, P.A.

San Antonio, Texas, United States

University of Washington Diabetes Institute

Seattle, Washington, United States

Mountain State Diabetes

Parkersburg, West Virginia, United States

Countries

United States

Other Identifiers

MKC-TI-193

Identifier Type: -

Identifier Source: org_study_id