Afrezza® INHALE-1 Study in Pediatrics

Diabetes Mellitus, Type 2 Clinical Trial

— INHALE-1  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04974528
• Other study ID #: MKC-TI-155 Part 2
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: September 29, 2021
• Est. completion date: April 2025

Study information

• Verified date: March 2024
• Source: Mannkind Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 319
• Est. completion date: April 2025
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Diabetes Mellitus, Type 2

Intervention

Biological:
• Afrezza
Pharmaceutical form: powder Route of administration: inhalation
• Rapid-acting Insulin Analog
Pharmaceutical form: clear and colorless solution for injection Route of administration: subcutaneous
• Basal Insulin
Pharmaceutical form: solution for injection Route of administration: subcutaneous

Locations

Country	Name	City	State
United States	Emory University, Children's Healthcare of Atlanta	Atlanta	Georgia
United States	Dr. Barry J. Reiner	Baltimore	Maryland
United States	Johns Hopkins University	Baltimore	Maryland
United States	AM Diabetes and Endocrinology Center	Bartlett	Tennessee
United States	Joslin Diabetes Center	Boston	Massachusetts
United States	UBMD Pediatrics Buffalo	Buffalo	New York
United States	Cincinnati Children's Hospital	Cincinnati	Ohio
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	UT Southwestern	Dallas	Texas
United States	DHR Health	Edinburg	Texas
United States	University of Florida	Gainesville	Florida
United States	Joe DiMaggio Children's Hospital	Hollywood	Florida
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	Children's Mercy Hospital	Kansas City	Missouri
United States	The DOCS	Las Vegas	Nevada
United States	Michigan Pediatric Endocrine and Diabetes Services	Livonia	Michigan
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	University of Louisville, Norton Children's Hospital	Louisville	Kentucky
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	University of Minnesota	Minneapolis	Minnesota
United States	Atlantic Health	Morristown	New Jersey
United States	Yale New Haven Hospital	New Haven	Connecticut
United States	NYU Langone, Hassenfeld Children's Hospital	New York	New York
United States	Oklahoma Children's Hospital	Oklahoma City	Oklahoma
United States	Children's Hospital of Orange County	Orange	California
United States	Advent Health Orlando	Orlando	Florida
United States	Stanford University	Palo Alto	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Sutter Institute for Medical Research (formerly Center of Excellence in Diabetes and Endocrinology)	Sacramento	California
United States	Children's Minnesota	Saint Paul	Minnesota
United States	Diabetes & Glandular Disease Clinic, DGD	San Antonio	Texas
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	Seattle Children's	Seattle	Washington
United States	University of South Florida	Tampa	Florida
United States	Iowa Diabetes Research, IDR	West Des Moines	Iowa
United States	Nemours Children's Hospital, Delaware	Wilmington	Delaware

Sponsors (2)

Lead Sponsor	Collaborator
Mannkind Corporation	Jaeb Center for Health Research

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Event rate of level 1 hypoglycemia (SMBG <70 mg/dL)	Event rate of level 1 hypoglycemia during the 26-week randomized treatment period	26 weeks
Other	Change in percent Time In Range (glucose 70 - 180 mg/dL)	Change in percent Time In Range from baseline to Week 26, using Continuous Glucose Monitoring (CGM)-derived data collected over the preceding 30 days for the 24-hour, daytime and nocturnal time periods	26 weeks
Other	Change in percent time with glucose <54 mg/dL	Change in percent time with glucose <54 mg/dL from baseline to Week 26, using CGM-derived data collected over the preceding 30 days for the 24-hour, daytime and nocturnal time periods	26 weeks
Other	Change in percent Time Below Range (glucose <70 mg/dL)	Change in percent Time Below Range from baseline to Week 26, using CGM-derived data collected over the preceding 30 days for the 24-hour, daytime and nocturnal time periods	26 weeks
Other	Change in percent Time Above Range (glucose >180 mg/dL)	Change in percent Time Above Range from baseline to Week 26, using CGM-derived data collected over the preceding 30 days for the 24-hour, daytime and nocturnal time periods	26 weeks
Other	Percentage of subjects with HbA1c <7.0%	Percentage of subjects with HbA1c <7.0% at Week 26	At Week 26
Other	Score of Diabetes Treatment Satisfaction Questionnaire (DTSQ) Change (c)-Teen	Score of DTSQ(c)-Teen at Week 26 in the Afrezza group (score ranges from -24 to 24, with higher score means greater satisfaction)	At Week 26
Other	Score of Diabetes Treatment Satisfaction Questionnaire (DTSQ) Change (c)-Parent	Score of DTSQ(c)-Parent at Week 26 in the Afrezza group (score ranges from -30 to 30, with higher score means greater satisfaction)	At Week 26
Other	Change in scores of DTSQ Status (s)-Teen	Change in scores of DTSQ(s)-Teen from baseline to Week 26 (change in score ranges from -48 to 48, with higher score means greater satisfaction)	26 weeks
Other	Change in scores of DTSQ Status (s)-Parent	Change in scores of DTSQ(s)-Parent from baseline to Week 26 (change in scores ranges from -60 to 60, with higher score means greater satisfaction)	26 weeks
Other	Change in HbA1c	Change in HbA1c from baseline to Week 52 (and change from Week 26 to Week 52 if required) in subjects who switch from treatment with RAA injections to Afrezza at Week 26	52 weeks (and 26 weeks if required)
Other	Change in FPG	Change in FPG from baseline to Week 52 (and change from Week 26 to Week 52 if required) in subjects who switch from treatment with RAA injections to Afrezza at Week 26	52 weeks (and 26 weeks if required)
Other	Change in percent Time In Range, Time Below Range and Time Above Range	Change in percent Time In Range, Time Below Range and Time Above Range from baseline to Week 52 (and change from Week 26 to Week 52 if required) in subjects who switch from treatment with RAA injections to Afrezza at Week 26; using CGM-derived data collected over the preceding 30 days for the 24-hour, daytime, and nocturnal periods	52 weeks (and 26 weeks if required)
Other	Change in HbA1c	Change in HbA1c from baseline to Week 52 in subjects who receive Afrezza in both the randomized treatment period and the treatment extension	52 weeks
Other	Change in FPG	Change in FPG from baseline to Week 52 in subjects who receive Afrezza in both the randomized treatment period and the treatment extension	52 weeks
Other	Change in percent Time In Range, Time Below Range and Time Above Range	Change in percent Time In Range, Time Below Range and Time Above Range from baseline to Week 52 in subjects who receive Afrezza in both the randomized treatment period and the treatment extension; using CGM-derived data collected over the preceding 30 days for the 24-hour, daytime, and nocturnal periods	52 weeks
Other	Score of DTSQ(c)-Teen at Week 52	Score of DTSQ(c)-Teen at Week 52 (after 6 months of Afrezza treatment) in subjects who switch from RAA injections to Afrezza (score ranges from -24 to 24, with higher score means greater satisfaction)	At Week 52
Other	Score of DTSQ(c)-Parent at Week 52	Score of DTSQ(c)-Parent at Week 52 (after 6 months of Afrezza treatment) in subjects who switch from RAA injections to Afrezza (score ranges from -30 to 30, with higher score means greater satisfaction)	At Week 52
Other	Change in scores of DTSQ(s)-Teen	Change in scores of DTSQ(s)-Teen from baseline to Week 52 (changes in score ranges from -48 to 48, with higher score means greater satisfaction)	52 weeks
Other	Change in scores of DTSQ(s)-Parent	Change in scores of DTSQ(s)-Parent from baseline to Week 52 (change in scores ranges from -60 to 60, with higher score means greater satisfaction)	52 weeks
Other	Event rates of hypoglycemic events	Event rates and incidence of total, nocturnal, and severe hypoglycemic events from baseline to Week 52	52 weeks
Other	Incidence of hypoglycemic events	Incidence of total, nocturnal, and severe hypoglycemic events from baseline to Week 52	52 weeks
Other	Incidence and severity of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	Incidence and severity of TEAEs and SAEs from baseline to Week 52	52 weeks
Other	Incidence and severity of Adverse Events of Special Interest (AESIs)	Incidence and severity of AESIs (i.e., acute bronchospasm, clinically relevant decline in pulmonary function [>15% decline from baseline percent predicted FEV1 accompanied by respiratory symptoms], hypersensitivity reactions [including anaphylaxis], use of asthma reliever medication, initiation or use of asthma controller medication, use of corticosteroid bursts, asthma exacerbations, hospitalization for asthma exacerbation, events of level 3 hypoglycemia, and diabetic ketoacidosis [DKA]) as well as the number of subjects with AESIs and number of individual events	52 weeks
Other	Change in percent predicted Forced Expiratory Volume in 1 Second (FEV1)	Change from baseline to Weeks 13, 26, 39, 52, and 56 in percent predicted FEV1	56 weeks
Primary	Change in HbA1c	Change in HbA1c from baseline to Week 26, for noninferiority assessment	26 weeks
Secondary	Change in Fasting Plasma Glucose (FPG)	Change in FPG from baseline to Week 26, for superiority assessment	26 weeks
Secondary	Event rate of pooled level 2 and level 3 hypoglycemia	Event rate of pooled level 2 and level 3 hypoglycemia (SMBG < 54 mg/dL and/or severe hypoglycemic events reported on the adverse event CRF) during the 26 -week randomized treatment period, for superiority assessment.	26 weeks
Secondary	Change in HbA1c	Change in HbA1c from baseline to Week 26, for superiority assessment	26 weeks