Diabetes Mellitus, Type 1
Conditions
Keywords
Diabetes Mellitus, Insulin, Inhaled, Afrezza, Technosphere, Adults, Degludec, Glucose sensors, Insulin pumps, CGM
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.
Interventions
BIOLOGICALAfrezza
Pharmaceutical form: powder Route of administration: inhalation
BIOLOGICALinsulin degludec
Pharmaceutical form: solution for injection Route of administration: subcutaneous
BIOLOGICALRapid-acting Insulin Analog
Pharmaceutical form: clear and colorless solution for injection Route of administration: subcutaneous
BIOLOGICALBasal Insulin
Pharmaceutical form: clear and colorless solution for injection Route of administration: subcutaneous
Sponsors
Jaeb Center for Health Research
Mannkind Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in glycated hemoglobin (HbA1c) | 17 weeks | Change in HbA1c from baseline to 17 weeks (non-inferiority margin 0.4%) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline to 17 weeks in Forced Expiratory Volume in one second (FEV1) | 17 weeks | Change from baseline to 17 weeks in FEV1 |
| 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) |
| 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 |
| 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 |
| 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) |
| 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) |
| Hyperglycemic events from logged blood glucose measurements (BGM) | 30 weeks | Hyperglycemic events from logged BGM measurements |
| Continuous Glucose Monitoring (CGM) measured percent time with glucose less than 54 mg/dL | 17 weeks | CGM-measured percent time with glucose \<54 mg/dL from baseline to 17 weeks (non-inferiority, margin 0.5%) |
| 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 |
| Mean Continuous Glucose Monitoring (CGM) glucose | 17 weeks | Mean CGM glucose 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 (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 |
| Change in glycated hemoglobin (HbA1c) for superiority assessment | 17 weeks | HbA1c 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 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 |
| 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% |
| 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 | 17 weeks | CGM-measured prolonged hyperglycemia events |
| Continuous Glucose Monitoring (CGM) measured hypoglycemia events | 17 weeks | CGM-measured hypoglycemia events |
| Standard Deviation (SD) of glucose | 17 weeks | SD of glucose |
| 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 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 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 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 with glucose less than 54 mg/dL less than1% | 17 weeks | Percent time with glucose \<54 mg/dL \<1% 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Weight | 17 weeks | Weight |
| Post prandial glucose for first meal challenge | 17 weeks | Post prandial glucose for first meal challenge |
| Area under the curve (AUC) for first meal challenge | 17 weeks | Area under the curve (AUC) for first meal challenge |
| Patient-reported outcome (PRO) questionnaires | 17 weeks | 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 |
| Change in HbA1c from baseline to 17 weeks, with a worsening of greater than 0.5% | 17 weeks | Additional binary HbA1c endpoints, HbA1c worsening from baseline to 17 weeks \>0.5% |
| Percent time in range (TIR) with glucose 70-180 mg/dL worsening from baseline to 17 weeks greater than or equal to 10% | 17 weeks | Additional binary CGM endpoints, Percent time in range with glucose 70-180 mg/dL worsening from baseline to 17 weeks ≥10% |
| Change in HbA1c from baseline to 17 weeks, with a worsening of greater than 1.0% | 17 weeks | Additional binary HbA1c endpoints, HbA1c worsening from baseline to 17 weeks \>1.0% |
| Percent time in range (TIR) with glucose 70-180 mg/dL worsening from baseline to 17 weeks greater than or equal to 5% | 17 weeks | Additional binary CGM endpoints, Percent time in range with glucose 70-180 mg/dL worsening from baseline to 17 weeks ≥5% |
Countries
United States
Outcome results
None listed