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

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

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.

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