INHALE-3: Afrezza® Combined With Insulin Degludec Versus Usual Care in Adults With Type 1 Diabetes
- Conditions
- Diabetes Mellitus, Type 1
- Interventions
- Biological: Rapid-acting Insulin AnalogBiological: AfrezzaBiological: Basal InsulinBiological: insulin degludec
- Registration Number
- NCT05904743
- Lead Sponsor
- Mannkind Corporation
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 141
-
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%
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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)
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No use of inhaled insulin in the 3 months prior to screening
-
If female of childbearing potential, willing and able to have pregnancy testing
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Investigator believes that the participant can safely use the study treatment and will follow protocol
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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
- 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Usual Care: Insulin delivery with either MDI, a pump without automation, or an AID system and CGM Rapid-acting Insulin Analog 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. Usual Care: Insulin delivery with either MDI, a pump without automation, or an AID system and CGM Basal Insulin 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. Afrezza (Technosphere Insulin) + insulin degludec Afrezza 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. Afrezza (Technosphere Insulin) + insulin degludec 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.
- Primary Outcome Measures
Name Time Method Change in glycated hemoglobin (HbA1c) 17 weeks Change in HbA1c from baseline to 17 weeks (non-inferiority margin 0.4%)
- Secondary Outcome Measures
Name Time Method Continuous Glucose Monitoring (CGM) measured percent time with glucose less than 70 mg/dL 17 weeks CGM-measured percent time with glucose \<70mg/dL from baseline to 17 weeks (non-inferiority, margin 2.0%)
Continuous Glucose Monitoring (CGM) measured daytime (0600-midnight) percent time in range with glucose 70-180 mg/dL 17 weeks CGM-measured daytime (0600-midnight) percent time in range with glucose 70-180 mg/dL from baseline to 17 weeks, for superiority assessment
Continuous Glucose Monitoring (CGM) measured time with glucose less than 54 mg/dL 17 weeks CGM-measured time with glucose \<54 mg/dL from baseline to 17 weeks, for superiority assessment
Continuous Glucose Monitoring (CGM) measured coefficient of variation 17 weeks CGM-measured coefficient of variation from baseline to 17 weeks, for superiority assessment
Percent time in range (TIR) with glucose 70-140 mg/dL 17 weeks Percent time in range with glucose 70-140 mg/dL
Percent time with glucose greater than 300 mg/dL 17 weeks Percent time with glucose \>300 mg/dL
Continuous Glucose Monitoring (CGM) measured prolonged hyperglycemia events 30 weeks CGM-measured prolonged hyperglycemia events
Standard Deviation (SD) of glucose 17 weeks SD of glucose
Continuous Glucose Monitoring (CGM) measured percent time with glucose less than 54 mg/dL 30 weeks CGM-measured percent time with glucose less than 54 mg/dL
Change in glycated hemoglobin (HbA1c) for superiority assessment 17 weeks HbA1c from baseline to 17 weeks, for superiority assessment
Change in HbA1c less than 7.0% at 17 weeks 17 weeks HbA1c \<7.0% at 17 weeks
Change in HbA1c from baseline to 17 weeks, with an improvement of greater than 0.5% 17 weeks HbA1c improvement from baseline to 17 weeks \>0.5%
Change in HbA1c from baseline to 17 weeks, with an improvement of greater than 1.0% 17 weeks HbA1c improvement from baseline to 17 weeks \>1.0%
Mean Continuous Glucose Monitoring (CGM) glucose 17 weeks Mean CGM glucose from baseline to 17 weeks, for superiority assessment
Continuous Glucose Monitoring (CGM) measured (24-hours) percent time in range (TIR) with glucose 70-180 mg/dL 17 weeks CGM-measured (24-hours) percent time in range with glucose 70-180 mg/dL from baseline to 17 weeks, for superiority assessment
Continuous Glucose Monitoring (CGM) measured percent time with glucose greater than 180 mg/dL 17 weeks CGM-measured percent time with glucose \> 180 mg/dL from baseline to 17 weeks, for superiority assessment
Continuous Glucose Monitoring (CGM) measured time with glucose greater than 250 mg/dL 17 weeks CGM-measured time with glucose \>250 mg/dL from baseline to 17 weeks, for superiority assessment
Continuous Glucose Monitoring (CGM) measured time with glucose less than 70 mg/dL 17 weeks CGM-measured time with glucose \<70 mg/dL from baseline to 17 weeks, for superiority assessment
Continuous Glucose Monitoring (CGM) measured hypoglycemia events 17 weeks CGM-measured hypoglycemia events
Percent time with glucose less than 54 mg/dL less than1% 17 weeks Percent time with glucose \<54 mg/dL \<1% at 17 weeks
"Fasting glucose" by Continuous Glucose Monitoring (CGM) 17 weeks "Fasting glucose" by CGM (defined as closest value to 6 a.m.; assumed, but not verified, with no food during the prior 4-hour period)
Percent time in range (TIR) with glucose 70-180 mg/dL greater than 70% 17 weeks Percent time in range with glucose 70-180 mg/dL \>70% at 17 weeks
Percent time in range (TIR) with glucose 70-180 mg/dL improvement from baseline to 17 weeks ≥10% 17 weeks Percent time in range with glucose 70-180 mg/dL improvement from baseline to 17 weeks ≥10%
Percent time in range (TIR) with glucose 70-180 mg/dL improvement from baseline to 17 weeks greater than or equal to 5% 17 weeks Percent time in range with glucose 70-180 mg/dL improvement from baseline to 17 weeks ≥5%
Percent time with glucose less than 70 mg/dL less than 4% 17 weeks Percent time with glucose \<70 mg/dL \<4% at 17 weeks
Percent time in range (TIR) 70-180 mg/dL greater than 70% and time less than 54 mg/dL less than 1% 17 weeks Percent time in range 70-180 mg/dL \>70% and time \<54 mg/dL \<1% at 17 weeks
Incidence of severe hypoglycemia events 30 weeks 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
Other serious adverse events, including hospitalizations 30 weeks Other serious adverse events, including hospitalizations
Incidence and severity of treatment-emergent adverse events (TEAEs) 30 weeks Incidence and severity of treatment-emergent adverse events (TEAEs)
Hypoglycemic events from logged blood glucose measurements (BGM): Level 1 events (less than 70 mg/dL) and Level 2 events (less than 54 mg/dL) separately 30 weeks Hypoglycemic events from logged BGM measurements: Level 1 events (\<70 mg/dL) and Level 2 events (\<54 mg/dL)
Change from baseline to 17 weeks in Forced Expiratory Volume in one second (FEV1) 17 weeks Change from baseline to 17 weeks in FEV1
Continuous Glucose Monitoring (CGM) measured hypoglycemia events (both a safety and efficacy endpoint) 30 weeks CGM-measured hypoglycemia events (both a safety and efficacy endpoint)
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 Incidence and severity of adverse events of special interest (AESIs) as well as the number of participants with AESIs and number of individual events
Hyperglycemic events from logged blood glucose measurements (BGM) 30 weeks Hyperglycemic events from logged BGM measurements
Proportion of participants with Forced Expiratory Volume in one second (FEV1) reduction greater than or equal to 20% 30 weeks Proportions of participants in each group who have experienced ≥20% reduction in FEV1 from baseline to Week 17
Trial Locations
- Locations (19)
Loma Linda University-Diabetes Treatment Center
🇺🇸Loma Linda, California, United States
Atlanta Diabetes Associates
🇺🇸Atlanta, Georgia, United States
Boston Medical Center
🇺🇸Boston, Massachusetts, United States
Joslin Diabetes Center
🇺🇸Boston, Massachusetts, United States
The University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Barbara Davis Center
🇺🇸Aurora, Colorado, United States
Sansum Diabetes Research
🇺🇸Santa Barbara, California, United States
Mount Sinai Diabetes Center
🇺🇸New York, New York, United States
University of Washington Diabetes Institute
🇺🇸Seattle, Washington, United States
Endocrine Associate of West Village, PC
🇺🇸Long Island City, New York, United States
Texas Diabetes & Endocrinology, P.A.
🇺🇸Austin, Texas, United States
Iowa Diabetes Research
🇺🇸West Des Moines, Iowa, United States
Northwestern University Division of Endocrinology, Metabolism and Molecular Medicine
🇺🇸Chicago, Illinois, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Diabetes and Glandular Disease Clinic, P.A.
🇺🇸San Antonio, Texas, United States
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Las Vegas Endocrinology
🇺🇸Henderson, Nevada, United States
Mountain State Diabetes
🇺🇸Parkersburg, West Virginia, United States