Afrezza® INHALE-1 Study in Pediatrics

NCT04974528 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: MKC-TI-155 Part 2
• Study Type: interventional
• Target: 319
• Locations: 1 country
• Sites: 39

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

Keywords

Diabetes Mellitus; Insulin; Inhaled; Afrezza; Technosphere; Pediatric

Outcome Measures

Primary Outcomes (1)

• Change in HbA1c

  Change in HbA1c from baseline to Week 26, for noninferiority assessment

  26 weeks

Secondary Outcomes (3)

• Change in Fasting Plasma Glucose (FPG)

  26 weeks

• Event rate of pooled level 2 and level 3 hypoglycemia

  26 weeks

• Change in HbA1c

  26 weeks

Other Outcomes (25)

• Event rate of level 1 hypoglycemia (SMBG <70 mg/dL)

  26 weeks

• Change in percent Time In Range (glucose 70 - 180 mg/dL)

  26 weeks

• Change in percent time with glucose <54 mg/dL

  26 weeks

Study Arms (2)

Afrezza (Technosphere Insulin) + Basal Insulin

EXPERIMENTAL

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.

Biological: Afrezza; Biological: Basal Insulin

RAA Injection + Basal Insulin

ACTIVE COMPARATOR

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.

Biological: Rapid-acting Insulin Analog; Biological: Basal Insulin

Interventions

Afrezza BIOLOGICAL

Pharmaceutical form: powder Route of administration: inhalation

Also known as: Technosphere Insulin

Afrezza (Technosphere Insulin) + Basal Insulin

Rapid-acting Insulin Analog BIOLOGICAL

Pharmaceutical form: clear and colorless solution for injection Route of administration: subcutaneous

Also known as: insulin aspart, insulin lispro, insulin glulisine, Novolog®, Fiasp®, Humalog®, Admelog®, Apidra®

RAA Injection + Basal Insulin

Basal Insulin BIOLOGICAL

Pharmaceutical form: solution for injection Route of administration: subcutaneous

Also known as: insulin glargine, insulin degludec, insulin detemir, Lantus®, Abasaglar®, Basaglar®, Semglee®, Toujeo®, Tresiba®, Levemir®

Afrezza (Technosphere Insulin) + Basal Insulin; RAA Injection + Basal Insulin

Eligibility Criteria

• Age: 4 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mannkind Corporation: lead
• Jaeb Center for Health Research: collaborator

Study Sites (39)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

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

Sacramento, California, 95821, United States

Location

University of California San Diego, Rady Children's Hospital

San Diego, California, 92123, United States

Location

University of California San Francisco

San Francisco, California, 94158, United States

Location

Yale New Haven Hospital

New Haven, Connecticut, 06511, United States

Location

Nemours Children's Hospital, Delaware

Wilmington, Delaware, 19803, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Joe DiMaggio Children's Hospital

Hollywood, Florida, 33021, United States

Location

Advent Health Orlando

Orlando, Florida, 32803, United States

Location

University of South Florida

Tampa, Florida, 33612, United States

Location

Emory University, Children's Healthcare of Atlanta

Atlanta, Georgia, 30329, United States

Location

Rocky Mountain Clinical Research

Idaho Falls, Idaho, 83404, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Iowa Diabetes Research, IDR

West Des Moines, Iowa, 50265, United States

Location

University of Louisville, Norton Children's Hospital

Louisville, Kentucky, 40202, United States

Location

Dr. Barry J. Reiner

Baltimore, Maryland, 21229, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Joslin Diabetes Center

Boston, Massachusetts, 02215, United States

Location

Michigan Pediatric Endocrine and Diabetes Services

Livonia, Michigan, 48152, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64111, United States

Location

The DOCS

Las Vegas, Nevada, 89113, United States

Location

Atlantic Health

Morristown, New Jersey, 07960, United States

Location

UBMD Pediatrics Buffalo

Buffalo, New York, 14203, United States

Location

NYU Langone, Hassenfeld Children's Hospital

New York, New York, 10016, United States

Location

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Oklahoma Children's Hospital

Oklahoma City, Oklahoma, 73104, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

AM Diabetes and Endocrinology Center

Bartlett, Tennessee, 38133, United States

Location

UT Southwestern

Dallas, Texas, 75390, United States

Location

DHR Health

Edinburg, Texas, 78539, United States

Location

Diabetes & Glandular Disease Clinic, DGD

San Antonio, Texas, 78229, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Seattle Children's

Seattle, Washington, 98105, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53201, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetes Mellitus; Insulin Resistance; Respiratory Aspiration

Interventions

Insulin; Insulin, Short-Acting; Insulin Aspart; Insulin Lispro; insulin glulisine; Insulin Glargine; insulin degludec; Insulin Detemir

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Hyperinsulinism; Respiration Disorders; Respiratory Tract Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Insulin, Long-Acting

Study Officials

• Kevin Kaiserman

  Mannkind Corporation

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2021
• First Posted: July 23, 2021
• Study Start: September 29, 2021
• Primary Completion: October 3, 2024
• Study Completion: April 29, 2025
• Last Updated: May 6, 2025

Record last verified: 2025-05

Locations

US (39)