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

NCT05904743 | Completed Phase 4 DMC FDA Drug

• 1 other identifier: MKC-TI-193
• Study Type: interventional
• Target: 141
• Locations: 1 country
• Sites: 19

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

Keywords

Diabetes Mellitus; Insulin; Inhaled; Afrezza; Technosphere; Adults; Degludec; Glucose sensors; Insulin pumps; CGM

Outcome Measures

Primary Outcomes (1)

• Change in glycated hemoglobin (HbA1c)

  Change in HbA1c from baseline to 17 weeks (non-inferiority margin 0.4%)

  17 weeks

Secondary Outcomes (37)

• Continuous Glucose Monitoring (CGM) measured percent time with glucose less than 54 mg/dL

  17 weeks

• Continuous Glucose Monitoring (CGM) measured percent time with glucose less than 70 mg/dL

  17 weeks

• Continuous Glucose Monitoring (CGM) measured daytime (0600-midnight) percent time in range with glucose 70-180 mg/dL

  17 weeks

• Mean Continuous Glucose Monitoring (CGM) glucose

  17 weeks

• Continuous Glucose Monitoring (CGM) measured (24-hours) percent time in range (TIR) with glucose 70-180 mg/dL

  17 weeks

Other Outcomes (8)

• Weight

  17 weeks

• Post prandial glucose for first meal challenge

  17 weeks

• Area under the curve (AUC) for first meal challenge

  17 weeks

Study Arms (2)

Afrezza (Technosphere Insulin) + insulin degludec

EXPERIMENTAL

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.

Biological: Afrezza; Biological: insulin degludec

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

ACTIVE COMPARATOR

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.

Biological: Rapid-acting Insulin Analog; Biological: Basal Insulin

Interventions

Afrezza BIOLOGICAL

Pharmaceutical form: powder Route of administration: inhalation

Also known as: Technosphere Insulin

Afrezza (Technosphere Insulin) + insulin degludec

insulin degludec BIOLOGICAL

Pharmaceutical form: solution for injection Route of administration: subcutaneous

Afrezza (Technosphere Insulin) + insulin degludec

Rapid-acting Insulin Analog BIOLOGICAL

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

Also known as: any FDA approved Rapid-acting Insulin Analog

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

Basal Insulin BIOLOGICAL

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

Also known as: any FDA approved Basal Insulin

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

Eligibility Criteria

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

You may qualify if:

• 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
• Current (at time of screening) rapid-acting insulin analog (RAA) in use for at least 4 weeks
• If AID system used, automated insulin delivery must be active \>85% of the time in the 4 weeks prior to screening
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mannkind Corporation: lead
• Jaeb Center for Health Research: collaborator

Study Sites (19)

Loma Linda University-Diabetes Treatment Center

Loma Linda, California, 92354, United States

Location

Sansum Diabetes Research

Santa Barbara, California, 93105, United States

Location

Barbara Davis Center

Aurora, Colorado, 80045, United States

Location

Atlanta Diabetes Associates

Atlanta, Georgia, 30318, United States

Location

Northwestern University Division of Endocrinology, Metabolism and Molecular Medicine

Chicago, Illinois, 60611, United States

Location

Iowa Diabetes Research

West Des Moines, Iowa, 50265, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Joslin Diabetes Center

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Las Vegas Endocrinology

Henderson, Nevada, 89074, United States

Location

Endocrine Associate of West Village, PC

Long Island City, New York, 11106, United States

Location

Mount Sinai Diabetes Center

New York, New York, 10075, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27514, United States

Location

Texas Diabetes & Endocrinology, P.A.

Austin, Texas, 78731, United States

Location

The University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Diabetes and Glandular Disease Clinic, P.A.

San Antonio, Texas, 78229, United States

Location

University of Washington Diabetes Institute

Seattle, Washington, 98119, United States

Location

Mountain State Diabetes

Parkersburg, West Virginia, 26101, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus; Insulin Resistance; Respiratory Aspiration

Interventions

Insulin; insulin degludec; Insulin, Short-Acting

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Hyperinsulinism; Respiration Disorders; Respiratory Tract Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Kevin Kaiserman, MD

  Mannkind Corporation

  STUDY DIRECTOR

• Irl B. Hirsch, MD

  University of Washington

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2023
• First Posted: June 15, 2023
• Study Start: July 7, 2023
• Primary Completion: March 26, 2024
• Study Completion: June 24, 2024
• Last Updated: August 9, 2024

Record last verified: 2024-08

Locations

US (19)