Clinical trial NCT05904743: INHALE-3: Afrezza® Combined With Insulin Degludec Versus Usual Care in Adults With Type 1 Diabetes
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetes Mellitus, Type 1
Keywords: Diabetes Mellitus
Insulin
Inhaled
Afrezza
Technosphere
Adults
Degludec
Glucose sensors
Insulin pumps
CGM
Lead sponsor: Mannkind Corporation
Sponsor class: INDUSTRY
Collaborators: name: Jaeb Center for Health Research
First posted: 2023-06-15
Enrollment: 141
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Change in glycated hemoglobin (HbA1c)
timeFrame: 17 weeks
Secondary outcomes:
measure: Continuous Glucose Monitoring (CGM) measured percent time with glucose less than 54 mg/dL
timeFrame: 17 weeks
measure: Continuous Glucose Monitoring (CGM) measured percent time with glucose less than 70 mg/dL
timeFrame: 17 weeks
measure: Continuous Glucose Monitoring (CGM) measured daytime (0600-midnight) percent time in range with glucose 70-180 mg/dL
timeFrame: 17 weeks
measure: Mean Continuous Glucose Monitoring (CGM) glucose
timeFrame: 17 weeks
measure: Continuous Glucose Monitoring (CGM) measured (24-hours) percent time in range (TIR) with glucose 70-180 mg/dL
timeFrame: 17 weeks
measure: Continuous Glucose Monitoring (CGM) measured percent time with glucose greater than 180 mg/dL
timeFrame: 17 weeks
measure: Change in glycated hemoglobin (HbA1c) for superiority assessment
timeFrame: 17 weeks
measure: Continuous Glucose Monitoring (CGM) measured time with glucose greater than 250 mg/dL
timeFrame: 17 weeks
measure: Continuous Glucose Monitoring (CGM) measured time with glucose less than 70 mg/dL
timeFrame: 17 weeks
measure: Continuous Glucose Monitoring (CGM) measured time with glucose less than 54 mg/dL
timeFrame: 17 weeks
measure: Continuous Glucose Monitoring (CGM) measured coefficient of variation
timeFrame: 17 weeks
measure: Change in HbA1c less than 7.0% at 17 weeks
timeFrame: 17 weeks
measure: Change in HbA1c from baseline to 17 weeks, with an improvement of greater than 0.5%
timeFrame: 17 weeks
measure: Change in HbA1c from baseline to 17 weeks, with an improvement of greater than 1.0%
timeFrame: 17 weeks
measure: Percent time in range (TIR) with glucose 70-140 mg/dL
timeFrame: 17 weeks
measure: Percent time with glucose greater than 300 mg/dL
timeFrame: 17 weeks
measure: Continuous Glucose Monitoring (CGM) measured prolonged hyperglycemia events
timeFrame: 17 weeks
measure: Continuous Glucose Monitoring (CGM) measured hypoglycemia events
timeFrame: 17 weeks
measure: Standard Deviation (SD) of glucose
timeFrame: 17 weeks
measure: "Fasting glucose" by Continuous Glucose Monitoring (CGM)
timeFrame: 17 weeks
measure: Percent time in range (TIR) with glucose 70-180 mg/dL greater than 70%
timeFrame: 17 weeks
measure: Percent time in range (TIR) with glucose 70-180 mg/dL improvement from baseline to 17 weeks greater than or equal to 5%
timeFrame: 17 weeks
measure: Percent time in range (TIR) with glucose 70-180 mg/dL improvement from baseline to 17 weeks ≥10%
timeFrame: 17 weeks
measure: Percent time with glucose less than 70 mg/dL less than 4%
timeFrame: 17 weeks
measure: Percent time with glucose less than 54 mg/dL less than1%
timeFrame: 17 weeks
measure: Percent time in range (TIR) 70-180 mg/dL greater than 70% and time less than 54 mg/dL less than 1%
timeFrame: 17 weeks
measure: Incidence of severe hypoglycemia events
timeFrame: 30 weeks
measure: Continuous Glucose Monitoring (CGM) measured percent time with glucose less than 54 mg/dL
timeFrame: 30 weeks
measure: Other serious adverse events, including hospitalizations
timeFrame: 30 weeks
measure: Incidence and severity of treatment-emergent adverse events (TEAEs)
timeFrame: 30 weeks
measure: Incidence and severity of adverse events of special interest (AESIs) as well as the number of participants with AESIs and number of individual events
timeFrame: 30 weeks
measure: Change from baseline to 17 weeks in Forced Expiratory Volume in one second (FEV1)
timeFrame: 17 weeks
measure: Proportion of participants with Forced Expiratory Volume in one second (FEV1) reduction greater than or equal to 20%
timeFrame: 30 weeks
measure: 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
timeFrame: 30 weeks
measure: Hyperglycemic events from logged blood glucose measurements (BGM)
timeFrame: 30 weeks
measure: Continuous Glucose Monitoring (CGM) measured prolonged hyperglycemia events
timeFrame: 30 weeks
measure: Continuous Glucose Monitoring (CGM) measured hypoglycemia events (both a safety and efficacy endpoint)
timeFrame: 30 weeks
Other outcomes:
measure: Weight
timeFrame: 17 weeks
measure: Post prandial glucose for first meal challenge
timeFrame: 17 weeks
measure: Area under the curve (AUC) for first meal challenge
timeFrame: 17 weeks
measure: Patient-reported outcome (PRO) questionnaires
timeFrame: 17 weeks
measure: Change in HbA1c from baseline to 17 weeks, with a worsening of greater than 0.5%
timeFrame: 17 weeks
measure: Change in HbA1c from baseline to 17 weeks, with a worsening of greater than 1.0%
timeFrame: 17 weeks
measure: Percent time in range (TIR) with glucose 70-180 mg/dL worsening from baseline to 17 weeks greater than or equal to 5%
timeFrame: 17 weeks
measure: Percent time in range (TIR) with glucose 70-180 mg/dL worsening from baseline to 17 weeks greater than or equal to 10%
timeFrame: 17 weeks
Locations:
city: Loma Linda
country: United States
facility: Loma Linda University-Diabetes Treatment Center
state: California
city: Santa Barbara
country: United States
facility: Sansum Diabetes Research
state: California
city: Aurora
country: United States
facility: Barbara Davis Center
state: Colorado
city: Atlanta
country: United States
facility: Atlanta Diabetes Associates
state: Georgia
city: Chicago
country: United States
facility: Northwestern University Division of Endocrinology, Metabolism and Molecular Medicine
state: Illinois
city: West Des Moines
country: United States
facility: Iowa Diabetes Research
state: Iowa
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Joslin Diabetes Center
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Henderson
country: United States
facility: Las Vegas Endocrinology
state: Nevada
city: Long Island City
country: United States
facility: Endocrine Associate of West Village, PC
state: New York
city: New York
country: United States
facility: Mount Sinai Diabetes Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Austin
country: United States
facility: Texas Diabetes & Endocrinology, P.A.
state: Texas
city: Dallas
country: United States
facility: The University of Texas Southwestern Medical Center
state: Texas
city: San Antonio
country: United States
facility: Diabetes and Glandular Disease Clinic, P.A.
state: Texas
city: Seattle
country: United States
facility: University of Washington Diabetes Institute
state: Washington
city: Parkersburg
country: United States
facility: Mountain State Diabetes
state: West Virginia
Study officials:
affiliation: Mannkind Corporation
name: Kevin Kaiserman, MD
role: STUDY_DIRECTOR
affiliation: University of Washington
name: Irl B. Hirsch, MD
role: STUDY_CHAIR
References: