Clinical trial NCT04974528: Afrezza® INHALE-1 Study in Pediatrics
Official title: INHALE-1: A 26-week Primary Treatment Phase, With 26-week Extension, Open-label, Randomized Clinical Trial Evaluating the Efficacy and Safety of Afrezza® Versus Rapid-acting Insulin Analog Injections, Both in Combination With a Basal Insulin, in Pediatric Subjects With Type 1 or Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 1
Diabetes Mellitus, Type 2
Keywords: Diabetes Mellitus
Insulin
Inhaled
Afrezza
Technosphere
Pediatric
Lead sponsor: Mannkind Corporation
Sponsor class: INDUSTRY
Collaborators: name: Jaeb Center for Health Research
First posted: 2021-07-23
Enrollment: 319
Sex: ALL
Minimum age (years): 4
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: INHALE-1 is a Phase 3, open-label, randomized clinical study evaluating the efficacy and safety of Afrezza in combination with a basal insulin (i.e., the Afrezza group) versus insulin aspart, insulin lispro or insulin glulisine in combination with a basal insulin (i.e., the Rapid-acting Insulin Analog \[RAA\] injection group) in pediatric subjects with type 1 or type 2 diabetes mellitus. Following 26 weeks of randomized treatment (i.e., Afrezza or RAA injection combined with a basal insulin), all subjects will enter a treatment extension where subjects will receive Afrezza until Week 52. The purpose of the treatment extension is to assess safety and efficacy with continued use of Afrezza.

Pediatric subjects ≥4 and \<18 years of age will be enrolled in this study. Subjects will be randomly assigned in a 1:1 ratio to either the Afrezza group or the RAA injection group.

The study is composed of:

* Up to 5-week screening/run-in period
* 26 week randomized treatment period
* 26-week treatment extension
* 4-week follow-up period


Eligibility criteria: Inclusion Criteria:

* Assent from the pediatric subject, as appropriate, and fully informed consent from the parent(s) or legal guardian, as required by both state and federal laws and the local Institutional Review Board (IRB)
* Subjects ≥4 and \<18 years of age
* Clinical diagnosis of type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) per the Investigator and have been using insulin for at least 6 months for T1DM, or at least 3 months for T2DM
* Treatment with basal-bolus insulin therapy delivered by multiple daily injections for at least 2 weeks
* Bolus insulins are restricted to the RAAs insulin lispro, insulin aspart or insulin glulisine, including biosimilar products
* Basal insulins are restricted to insulin glargine, insulin degludec or insulin detemir, including biosimilar products
* Access to stable WiFi connection
* HbA1c ≥7.0% and ≤11%
* Average prandial dose of insulin ≥2 units per meal
* Utilized CGM for ≥70% of the time over a consecutive 14-day period preceding randomization

Exclusion Criteria:

* History of recent blood transfusions (within previous 3 months), hemoglobinopathies, or any other conditions that affect HbA1c measurements
* Recent history of asthma (defined as using any medications to treat within the last year), any other clinically important pulmonary disease (e.g., cystic fibrosis or bronchopulmonary dysplasia), or significant congenital or acquired cardiopulmonary disease
* History of serious complications of diabetes (e.g., active proliferative retinopathy or symptomatic autonomic neuropathy), or likely need for specific treatment for diabetic retinopathy (laser photocoagulation, vitrectomy, other) in the next year
* FEV1 and FEV1/forced vital capacity (FVC) ≤80% of predicted Global Lung Function Initiative (GLI) value
* Inability to achieve an acceptable FEV1 and FVC reading for subjects ≥8 years of age would make the subject ineligible
* For subjects \<8 years of age who are unable to achieve an acceptable FVC reading, FEV1 only may be assessed; inability to achieve an acceptable FEV1 would make the subject ineligible
* Respiratory tract infection within 14 days before screening (subject may return 14 days after resolution of symptoms for rescreening)
* Inability or unwillingness to perform study procedures
* Exposure to any investigational product(s), including drugs or devices, in the past 30 days
* Any disease other than diabetes or exposure to any medication that, in the judgment of the Investigator, may impact glucose metabolism and current or anticipated acute uses of glucocorticoids or weight loss medications, with the exception of metformin and/or GLP-1 agonists (if GLP-1 agonists used for at least the 3 months prior to enrollment) in subjects with T2DM
* Use of antiadrenergic drugs (e.g., clonidine)
* Any concurrent illness (other than diabetes mellitus) not controlled by a stable therapeutic regimen
* Current uncontrolled eating disorder (e.g., anorexia or bulimia nervosa)
* Current drug or alcohol abuse or a history of drug or alcohol abuse that, in the opinion of the Investigator or the Sponsor, would make the subject an unsuitable candidate for participation in the study
* Smoking (includes cigarettes, cigars, pipes, marijuana, and vaping devices) for the preceding 6 months and/or positive urine cotinine test
* Female subject who is pregnant, breast-feeding, intends to become pregnant, or is of child-bearing potential, sexually active and not using adequate contraceptive methods as required by local regulation or practice
* An event of severe hypoglycemia, as judged by the Investigator, within the last 90 days prior to screening
* An episode of DKA requiring hospitalization within the last 90 days prior to screening

Primary outcomes:
measure: Change in HbA1c
timeFrame: 26 weeks
Secondary outcomes:
measure: Change in Fasting Plasma Glucose (FPG)
timeFrame: 26 weeks
measure: Event rate of pooled level 2 and level 3 hypoglycemia
timeFrame: 26 weeks
measure: Change in HbA1c
timeFrame: 26 weeks
Other outcomes:
measure: Event rate of level 1 hypoglycemia (SMBG <70 mg/dL)
timeFrame: 26 weeks
measure: Change in percent Time In Range (glucose 70 - 180 mg/dL)
timeFrame: 26 weeks
measure: Change in percent time with glucose <54 mg/dL
timeFrame: 26 weeks
measure: Change in percent Time Below Range (glucose <70 mg/dL)
timeFrame: 26 weeks
measure: Change in percent Time Above Range (glucose >180 mg/dL)
timeFrame: 26 weeks
measure: Percentage of subjects with HbA1c <7.0%
timeFrame: At Week 26
measure: Score of Diabetes Treatment Satisfaction Questionnaire (DTSQ) Change (c)-Teen
timeFrame: At Week 26
measure: Score of Diabetes Treatment Satisfaction Questionnaire (DTSQ) Change (c)-Parent
timeFrame: At Week 26
measure: Change in scores of DTSQ Status (s)-Teen
timeFrame: 26 weeks
measure: Change in scores of DTSQ Status (s)-Parent
timeFrame: 26 weeks
measure: Change in HbA1c
timeFrame: 52 weeks (and 26 weeks if required)
measure: Change in FPG
timeFrame: 52 weeks (and 26 weeks if required)
measure: Change in percent Time In Range, Time Below Range and Time Above Range
timeFrame: 52 weeks (and 26 weeks if required)
measure: Change in HbA1c
timeFrame: 52 weeks
measure: Change in FPG
timeFrame: 52 weeks
measure: Change in percent Time In Range, Time Below Range and Time Above Range
timeFrame: 52 weeks
measure: Score of DTSQ(c)-Teen at Week 52
timeFrame: At Week 52
measure: Score of DTSQ(c)-Parent at Week 52
timeFrame: At Week 52
measure: Change in scores of DTSQ(s)-Teen
timeFrame: 52 weeks
measure: Change in scores of DTSQ(s)-Parent
timeFrame: 52 weeks
measure: Event rates of hypoglycemic events
timeFrame: 52 weeks
measure: Incidence of hypoglycemic events
timeFrame: 52 weeks
measure: Incidence and severity of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: 52 weeks
measure: Incidence and severity of Adverse Events of Special Interest (AESIs)
timeFrame: 52 weeks
measure: Change in percent predicted Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: 56 weeks
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Sacramento
country: United States
facility: Sutter Institute for Medical Research (formerly Center of Excellence in Diabetes and Endocrinology)
state: California
city: San Diego
country: United States
facility: University of California San Diego, Rady Children's Hospital
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Wilmington
country: United States
facility: Nemours Children's Hospital, Delaware
state: Delaware
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Hollywood
country: United States
facility: Joe DiMaggio Children's Hospital
state: Florida
city: Orlando
country: United States
facility: Advent Health Orlando
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Atlanta
country: United States
facility: Emory University, Children's Healthcare of Atlanta
state: Georgia
city: Idaho Falls
country: United States
facility: Rocky Mountain Clinical Research
state: Idaho
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: West Des Moines
country: United States
facility: Iowa Diabetes Research, IDR
state: Iowa
city: Louisville
country: United States
facility: University of Louisville, Norton Children's Hospital
state: Kentucky
city: Baltimore
country: United States
facility: Dr. Barry J. Reiner
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Joslin Diabetes Center
state: Massachusetts
city: Livonia
country: United States
facility: Michigan Pediatric Endocrine and Diabetes Services
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: Las Vegas
country: United States
facility: The DOCS
state: Nevada
city: Morristown
country: United States
facility: Atlantic Health
state: New Jersey
city: Buffalo
country: United States
facility: UBMD Pediatrics Buffalo
state: New York
city: New York
country: United States
facility: NYU Langone, Hassenfeld Children's Hospital
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Children's Hospital
state: Oklahoma
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Bartlett
country: United States
facility: AM Diabetes and Endocrinology Center
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern
state: Texas
city: Edinburg
country: United States
facility: DHR Health
state: Texas
city: San Antonio
country: United States
facility: Diabetes & Glandular Disease Clinic, DGD
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Mannkind Corporation
name: Kevin Kaiserman
role: STUDY_DIRECTOR
References: