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

Diabetes Mellitus, Type 1 Clinical Trial

Official title:

INHALE-3: A 17-Week Randomized Trial and a 13-Week Extension, Evaluating the Efficacy and Safety of Inhaled Insulin (Afrezza) Combined With Insulin Degludec Versus Usual Care in Adults With Type 1 Diabetes

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05904743
• Other study ID #: MKC-TI-193
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: July 7, 2023
• Est. completion date: October 2024

Study information

• Verified date: June 2023
• Source: Mannkind Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 141
• Est. completion date: October 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1

Intervention

Biological:
• Afrezza
Pharmaceutical form: powder Route of administration: inhalation
• insulin degludec
Pharmaceutical form: solution for injection Route of administration: subcutaneous
• Rapid-acting Insulin Analog
Pharmaceutical form: clear and colorless solution for injection Route of administration: subcutaneous
• Basal Insulin
Pharmaceutical form: clear and colorless solution for injection Route of administration: subcutaneous

Locations

Country	Name	City	State
United States	Atlanta Diabetes Associates	Atlanta	Georgia
United States	Barbara Davis Center	Aurora	Colorado
United States	Texas Diabetes & Endocrinology, P.A.	Austin	Texas
United States	Boston Medical Center	Boston	Massachusetts
United States	Joslin Diabetes Center	Boston	Massachusetts
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Northwestern University Division of Endocrinology, Metabolism and Molecular Medicine	Chicago	Illinois
United States	The University of Texas Southwestern Medical Center	Dallas	Texas
United States	Las Vegas Endocrinology	Henderson	Nevada
United States	Loma Linda University-Diabetes Treatment Center	Loma Linda	California
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	Mountain State Diabetes	Parkersburg	West Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	Diabetes and Glandular Disease Clinic, P.A.	San Antonio	Texas
United States	Sansum Diabetes Research	Santa Barbara	California
United States	University of Washington Diabetes Institute	Seattle	Washington
United States	SUNY Upstate Medical University	Syracuse	New York
United States	Iowa Diabetes Research	West Des Moines	Iowa

Sponsors (2)

Lead Sponsor	Collaborator
Mannkind Corporation	Jaeb Center for Health Research

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Weight	Weight	17 weeks
Other	Post prandial glucose for first meal challenge	Post prandial glucose for first meal challenge	17 weeks
Other	Area under the curve (AUC) for first meal challenge	Area under the curve (AUC) for first meal challenge	17 weeks
Other	Patient-reported outcome (PRO) questionnaires	Type 1 Diabetes Distress Scale (T1-DDS): 28-item validated survey pertaining to distress symptoms related to diabetes (recorded from a scale of 1 to 6).; Hypoglycemia Confidence Scale (HCS): 9-item validated survey pertaining to situations where hypoglycemia could occur and queries about the participant's level of confidence in those situations (recorded from a scale 1 to 4).; Insulin Treatment Satisfaction Questionnaire (ITSQ): 22-item survey with a 5-factor structure assessing insulin satisfaction (scores range from 0 to 100).; Freedom and Flexibility: 6-item non-validated survey pertaining to life experiences impacted by having diabetes (scores range from 6 to 36); Insulin Adherence: 1-item non-validated survey pertaining to number of missed boluses in the past week	17 weeks
Primary	Change in HbA1c	Change in HbA1c from baseline to 17 weeks (non-inferiority, non-inferiority margin 0.4%)	17 weeks
Secondary	CGM-measured percent time with glucose <54 mg/dL	CGM-measured percent time with glucose <54 mg/dL from baseline to 17 weeks (non-inferiority, margin 0.5%)	17 weeks
Secondary	CGM-measured percent time with glucose <70 mg/dL	CGM-measured percent time with glucose <70mg/dL from baseline to 17 weeks (non-inferiority, margin 2.0%)	17 weeks
Secondary	CGM-measured daytime (0600-midnight) percent time in range with glucose 70-180 mg/dL	CGM-measured daytime (0600-midnight) percent time in range with glucose 70-180 mg/dL from baseline to 17 weeks, for superiority assessment	17 weeks
Secondary	Mean CGM glucose	Mean CGM glucose from baseline to 17 weeks, for superiority assessment	17 weeks
Secondary	CGM-measured (24-hours) percent time in range with glucose 70-180 mg/dL	CGM-measured (24-hours) percent time in range with glucose 70-180 mg/dL from baseline to 17 weeks, for superiority assessment	17 weeks
Secondary	CGM-measured percent time with glucose >180 mg/dL	CGM-measured percent time with glucose > 180 mg/dL from baseline to 17 weeks, for superiority assessment	17 weeks
Secondary	HbA1c	HbA1c from baseline to 17 weeks, for superiority assessment	17 weeks
Secondary	CGM-measured time with glucose >250 mg/dL	CGM-measured time with glucose >250 mg/dL from baseline to 17 weeks, for superiority assessment	17 weeks
Secondary	CGM-measured time with glucose <70 mg/dL	CGM-measured time with glucose <70 mg/dL from baseline to 17 weeks, for superiority assessment	17 weeks
Secondary	CGM-measured time with glucose <54 mg/dL	CGM-measured time with glucose <54 mg/dL from baseline to 17 weeks, for superiority assessment	17 weeks
Secondary	CGM-measured coefficient of variation	CGM-measured coefficient of variation from baseline to 17 weeks, for superiority assessment	17 weeks
Secondary	Incidence of severe hypoglycemia events	Incidence of severe hypoclycemia events, defined as events requiring assistance of another person due to cognitive impairment to actively administer carbohydrate, glucagon, or other resuscitative actions	30 weeks
Secondary	CGM-measured percent time with glucose <54 mg/dL	CGM-measured percent time with glucose <54 mg/dL	30 weeks
Secondary	Other serious adverse events, including hospitalizations	Other serious adverse events, including hospitalizations	30 weeks
Secondary	Incidence and severity of treatment-emergent adverse events (TEAEs)	Incidence and severity of treatment-emergent adverse events (TEAEs)	30 weeks
Secondary	Incidence and severity of adverse events of special interest (AESIs) as well as the number of participants with AESIs and number of individual events	Incidence and severity of adverse events of special interest (AESIs) as well as the number of participants with AESIs and number of individual events	30 weeks
Secondary	Change from baseline to 17 weeks in FEV1	Change from baseline to 17 weeks in FEV1	17 weeks
Secondary	Proportions of participants in each group who have experienced =20% reduction in FEV1 from baseline to Week 17	Proportions of participants in each group who have experienced =20% reduction in FEV1 from baseline to Week 17	30 weeks
Secondary	Hypoglycemic events from logged BGM measurements: Level 1 events (<70 mg/dL) and Level 2 events (<54 mg/dL) separately	Hypoglycemic events from logged BGM measurements: Level 1 events (<70 mg/dL) and Level 2 events (<54 mg/dL)	30 weeks
Secondary	Hyperglycemic events from logged BGM measurements	Hyperglycemic events from logged BGM measurements	30 weeks
Secondary	CGM-measured prolonged hyperglycemia events	CGM-measured prolonged hyperglycemia events	30 weeks
Secondary	CGM-measured hypoglycemia events (both a safety and efficacy endpoint)	CGM-measured hypoglycemia events (both a safety and efficacy endpoint)	17 weeks