Afrezza® INHALE-1 Study in Pediatrics

NCT ID: NCT04974528

Last Updated: 2025-05-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 319 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-29
• Study Completion Date: 2025-04-29

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

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Afrezza (Technosphere Insulin) + Basal Insulin

Individualized dose of Afrezza (Technosphere Insulin) for each patient before each meal (breakfast, lunch, and dinner) for 26 weeks.

Individualized basal insulin (insulin degludec, insulin glargine or insulin detemir) for each patient.

Group Type: EXPERIMENTAL

Afrezza

Intervention Type: BIOLOGICAL

Pharmaceutical form: powder

Route of administration: inhalation

Basal Insulin

Intervention Type: BIOLOGICAL

Pharmaceutical form: solution for injection

Route of administration: subcutaneous

RAA Injection + Basal Insulin

Individualized dose of RAA injection (insulin aspart, insulin lispro or insulin glulisine) for each patient for 26 weeks.

Individualized basal insulin (insulin degludec, insulin glargine or insulin detemir) for each patient.

Group Type: ACTIVE_COMPARATOR

Rapid-acting Insulin Analog

Intervention Type: BIOLOGICAL

Pharmaceutical form: clear and colorless solution for injection

Route of administration: subcutaneous

Basal Insulin

Intervention Type: BIOLOGICAL

Pharmaceutical form: solution for injection

Route of administration: subcutaneous

Interventions

Afrezza

Pharmaceutical form: powder

Route of administration: inhalation

Intervention Type: BIOLOGICAL

Rapid-acting Insulin Analog

Pharmaceutical form: clear and colorless solution for injection

Route of administration: subcutaneous

Intervention Type: BIOLOGICAL

Basal Insulin

Pharmaceutical form: solution for injection

Route of administration: subcutaneous

Intervention Type: BIOLOGICAL

Other Intervention Names

Technosphere Insulin; insulin aspart; insulin lispro; insulin glulisine; Novolog®; Fiasp®; Humalog®; Admelog®; Apidra®; insulin glargine; insulin degludec; insulin detemir; Lantus®; Abasaglar®; Basaglar®; Semglee®; Toujeo®; Tresiba®; Levemir®

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

• Minimum Eligible Age: 4 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jaeb Center for Health Research

OTHER

Sponsor Role: collaborator

Mannkind Corporation

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kevin Kaiserman

Role: STUDY_DIRECTOR

Mannkind Corporation

Locations

Children's Hospital Los Angeles

Los Angeles, California, United States

Children's Hospital of Orange County

Orange, California, United States

Stanford University

Palo Alto, California, United States

Sutter Institute for Medical Research (formerly Center of Excellence in Diabetes and Endocrinology)

Sacramento, California, United States

University of California San Diego, Rady Children's Hospital

San Diego, California, United States

University of California San Francisco

San Francisco, California, United States

Yale New Haven Hospital

New Haven, Connecticut, United States

Nemours Children's Hospital, Delaware

Wilmington, Delaware, United States

University of Florida

Gainesville, Florida, United States

Joe DiMaggio Children's Hospital

Hollywood, Florida, United States

Advent Health Orlando

Orlando, Florida, United States

University of South Florida

Tampa, Florida, United States

Emory University, Children's Healthcare of Atlanta

Atlanta, Georgia, United States

Rocky Mountain Clinical Research

Idaho Falls, Idaho, United States

Indiana University

Indianapolis, Indiana, United States

University of Iowa

Iowa City, Iowa, United States

Iowa Diabetes Research, IDR

West Des Moines, Iowa, United States

University of Louisville, Norton Children's Hospital

Louisville, Kentucky, United States

Dr. Barry J. Reiner

Baltimore, Maryland, United States

Johns Hopkins University

Baltimore, Maryland, United States

Joslin Diabetes Center

Boston, Massachusetts, United States

Michigan Pediatric Endocrine and Diabetes Services

Livonia, Michigan, United States

University of Minnesota

Minneapolis, Minnesota, United States

Children's Mercy Hospital

Kansas City, Missouri, United States

The DOCS

Las Vegas, Nevada, United States

Atlantic Health

Morristown, New Jersey, United States

UBMD Pediatrics Buffalo

Buffalo, New York, United States

NYU Langone, Hassenfeld Children's Hospital

New York, New York, United States

Cincinnati Children's Hospital

Cincinnati, Ohio, United States

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Oklahoma Children's Hospital

Oklahoma City, Oklahoma, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

AM Diabetes and Endocrinology Center

Bartlett, Tennessee, United States

UT Southwestern

Dallas, Texas, United States

DHR Health

Edinburg, Texas, United States

Diabetes & Glandular Disease Clinic, DGD

San Antonio, Texas, United States

Virginia Commonwealth University

Richmond, Virginia, United States

Seattle Children's

Seattle, Washington, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

Other Identifiers

MKC-TI-155 Part 2

Identifier Type: -

Identifier Source: org_study_id