Afrezza® INHALE-1 Study in Pediatrics

Sponsor
Mannkind Corporation (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04974528
Collaborator
Jaeb Center for Health Research (Other)
264
Enrollment
13
Locations
2
Arms
30.1
Anticipated Duration (Months)
20.3
Patients Per Site
0.7
Patients Per Site Per Month

Study Details

Study Description

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 or insulin lispro in combination with a basal insulin (i.e., the 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 4-week screening/run-in period

  • 26 week randomized treatment period

  • 26-week treatment extension

  • 4-week follow-up period

Condition or DiseaseIntervention/TreatmentPhase
  • Biological: Afrezza
  • Biological: Rapid-Acting Insulin Analog
  • Biological: Basal Insulin
Phase 3

Study Design

Study Type:
Interventional
Anticipated Enrollment :
264 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Sep 29, 2021
Anticipated Primary Completion Date :
Apr 1, 2023
Anticipated Study Completion Date :
Apr 1, 2024

Arms and Interventions

ArmIntervention/Treatment
Experimental: 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 or glargine) for each patient as 1 dose in the evening.

Biological: Afrezza
Pharmaceutical form: powder Route of administration: inhalation
Other Names:
  • Technosphere Insulin
  • Biological: Basal Insulin
    Pharmaceutical form: solution for injection Route of administration: subcutaneous
    Other Names:
  • insulin glargine
  • insulin degludec
  • Lantus
  • Tresiba
  • Active Comparator: RAA Injection + Basal Insulin

    Individualized dose of RAA injection (insulin aspart or lispro) for each patient for 26 weeks. Individualized basal insulin (insulin degludec or glargine) for each patient as 1 dose in the evening.

    Biological: Rapid-Acting Insulin Analog
    Pharmaceutical form: clear and colorless solution for injection Route of administration: subcutaneous
    Other Names:
  • insulin aspart
  • insulin lispro
  • Novolog
  • Humalog U-100
  • Admelog
  • Biological: Basal Insulin
    Pharmaceutical form: solution for injection Route of administration: subcutaneous
    Other Names:
  • insulin glargine
  • insulin degludec
  • Lantus
  • Tresiba
  • Outcome Measures

    Primary Outcome Measures

    1. Change in HbA1c After 26 Weeks [26 weeks]

      HbA1c change after 26 weeks of Afrezza compared to Rapid-Acting Analog (RAA)

    Secondary Outcome Measures

    1. Change in Fasting Plasma Glucose (FPG) After 26 weeks [26 weeks]

      FPG change after 26 weeks of Afrezza compared to Rapid-Acting Analog (RAA)

    2. Rate of Hypoglycemic Events After 26 weeks [26 weeks]

      Event rate of hypoglycemia (SMBG <70 mg/dL) after 26 weeks of Afrezza compared to Rapid-Acting Analog (RAA).

    Other Outcome Measures

    1. Time in Range (70 - 180 mg/dL) [26 weeks]

      Time in Range after 26 weeks of Afrezza compared to Rapid-Acting Analog (RAA), based on continuous glucose monitoring derived glucose values.

    2. Change in Percent Time with Glucose <54 mg/dL [26 weeks]

      Percent Time with Glucose <54 mg/dL after 26 weeks of Afrezza compared to Rapid-Acting Analog (RAA), based on continuous glucose monitoring derived values.

    3. Time Below Range (glucose <70 mg/dL) [26 weeks]

      Time Below Range after 26 weeks of Afrezza compared to Rapid-Acting Analog (RAA), based on continuous glucose monitoring derived values.

    4. Time Above Range (glucose >180 mg/dL) [26 weeks]

      Percent Time with Glucose >180 mg/dL after 26 weeks of Afrezza compared to Rapid-Acting Analog (RAA), based on continuous glucose monitoring derived values.

    5. Percentage of Subjects with HbA1c <7.0% at Week 26 [26 weeks]

      Percentage of Subjects with HbA1c <7.0% after 26 weeks of Afrezza compared to Rapid-Acting Analog (RAA).

    6. Change in DTSQ score After 26 Weeks of Afrezza [26 weeks]

      Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ) score from before the first dose of Afrezza until after 26 weeks of Afrezza therapy (Week 26 for the Afrezza arm, or Week 52 for the RAA Arm). Scores range from -18 to 18, with higher scores indicating greater treatment satisfaction.

    7. Change in HbA1c During Extension - RAA arm [During treatment extension at week 26 to week 52]

      Change in HbA1c from Week 26 to Week 52 for the RAA arm only (the RAA arm switches to Afrezza at Week 26)

    8. Change in HbA1c After 52 Weeks - Afrezza arm [52 weeks]

      Change in HbA1c from baseline to week 52, in subjects who received Afrezza in both the randomized treatment period and the treatment extension.

    9. Event Rate of Hypoglycemic Events After 52 Weeks [52 weeks]

      Event rate of total, nocturnal, and severe hypoglycemic events; based on the International Society for Pediatric and Adolescent Diabetes criteria.

    10. Incidence of Hypoglycemic Events After 52 Weeks [52 weeks]

      Incidence of total, nocturnal, and severe hypoglycemic events; based on the International Society for Pediatric and Adolescent Diabetes criteria.

    11. Incidence and Severity of Adverse Events [52 weeks]

      Incidence and severity of adverse events (AEs): treatment-emergent adverse events (TEAEs), serious AEs (SAEs), and AEs of special interest (AESIs).

    12. Change in Percent Predicted Forced Expiratory Volume in 1 Second [56 weeks]

      Change in percent predicted forced expiratory volume in 1 second (FEV1) from baseline to Weeks 13, 26, 39, 52, and 56.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    4 Years to 17 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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:

    • Acceptable bolus insulins are restricted to the RAAs insulin lispro or insulin aspart, including biosimilar products.

    • Basal insulins are restricted to 100-U/mL formulations of insulin glargine or insulin degludec, including biosimilar products.

    • Access to stable WiFi connection

    • HbA1c ≥7.0% and ≤11%

    • Average prandial dose of insulin ≥2 units per meal

    • Utilized continuous glucose monitor (CGM) for ≥70% of the time over a 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

    • History of asthma, any other clinically important pulmonary disease (e.g., cystic fibrosis or bronchopulmonary dysplasia), use of any medications to treat such conditions within the last year, 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 or between the screening and randomization visits (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, including liraglutide, and current or anticipated acute uses of glucocorticoids or weight loss medications, with the exception of metformin 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

    • History of a significant 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 diabetic ketoacidosis (DKA) requiring hospitalization within the last 90 days prior to screening

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Children's Hospital Los AngelesLos AngelesCaliforniaUnited States90027
    2University of FloridaGainesvilleFloridaUnited States32610
    3University of South FloridaTampaFloridaUnited States33612
    4Indiana UniversityIndianapolisIndianaUnited States45202
    5University of IowaIowa CityIowaUnited States52242
    6University of Louisville Research Foundation/KCPCRULouisvilleKentuckyUnited States40202
    7Joslin Diabetes CenterBostonMassachusettsUnited States02215
    8The DOCSLas VegasNevadaUnited States89113
    9UBMD Pediatrics Endocrinology/DiabetesBuffaloNew YorkUnited States14203
    10University Hospitals Cleveland Medical Center - Rainbow Babies and Children's HospitalClevelandOhioUnited States44106
    11Children's Hospital of PhiladelphiaPhiladelphiaPennsylvaniaUnited States19104
    12AM Diabetes and Endocrinology CenterBartlettTennesseeUnited States38133
    13Diabetes & Glandular Disease ClinicSan AntonioTexasUnited States78229

    Sponsors and Collaborators

    • Mannkind Corporation
    • Jaeb Center for Health Research

    Investigators

    • Study Director: Kevin Kaiserman, Mannkind Corporation
    • Study Director: Karen Jaffe, Mannkind Corporation

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Mannkind Corporation
    ClinicalTrials.gov Identifier:
    NCT04974528
    Other Study ID Numbers:
    • MKC-TI-155 Part 2
    First Posted:
    Jul 23, 2021
    Last Update Posted:
    Nov 24, 2021
    Last Verified:
    Nov 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Mannkind Corporation
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Nov 24, 2021