Study of HDV Insulin Versus Insulin in Type 1 Diabetes Subjects (ISLE-1)
Condition: Type 1 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Study type: Interventional
Phase: Phase 2

Summary: 
      This will be a Phase 2b, multicenter, randomized, double blind, titration clinical study,
      evaluating the efficacy and safety in the HDV Insulin Lispro Group versus Insulin Lispro
      Group in patients with type 1 diabetes over a 26 week treatment period. The patients will be
      randomized using a centrally allocated randomization scheme to 1 of the 2 treatment arms in
      an overall 2:1 scheme (HDV Insulin Lispro: Insulin Lispro). Both arms will receive the
      randomized treatment in combination with glargine or detemir. Goal to demonstrate that the
      efficacy of HDV insulin lispro administered in combination with a basal insulin (HDV Insulin
      Lispro group) is non-inferior to insulin lispro in combination with a basal insulin (Insulin
      Lispro group), in effects on glycated hemoglobin (HbA1c) in patients with type 1 diabetes. If
      non-inferiority is demonstrated, confirm that HDV insulin lispro in combination with a basal
      insulin (HDV Insulin Lispro group) is superior to insulin lispro in combination with a basal
      insulin (Insulin Lispro group), in effects on HbA1c in patients with type 1 diabetes (≥ 0.4%
      decrease in HbA1c).
    

Detailed description: 
      This will be a Phase 2b, multicenter, randomized, double blind, titration clinical study,
      evaluating the efficacy and safety in the HDV Insulin Lispro Group versus Insulin Lispro
      Group in patients with type 1 diabetes over a 26 week treatment period. The patients will be
      randomized using a centrally allocated randomization scheme to 1 of the 2 treatment arms in
      an overall 2:1 scheme (HDV Insulin Lispro: Insulin Lispro). Both arms will receive the
      randomized treatment in combination with glargine or detemir.

      SCREENING (Visit 1, Week -4 to -1) Patients will arrive for Screening following an 8 hour
      fast. During Screening, patients will sign the informed consent form, be reviewed for
      inclusion/exclusion, and provide medical history, concomitant medications, and demographics.
      They will have a brief physical exam and provide vital signs. Safety
      hematology/chemistry/urinalysis (with liver enzymes) will include infectious serology, and
      serum pregnancy test for women of childbearing potential. An ECG will be performed and
      patients will provide samples for HbA1c determination.

      Patients taking lispro/glargine or lispro/detemir at the time of Screening and who meet all
      eligibility criteria will proceed to Visit 2 (Week -1).

      TREATMENT PERIOD Visit 1a (Week -2) will be required only if a patient must convert to lispro
      prior to Visit 3 (Week 0, randomization). Patients taking non-lispro/glargine or
      non-lispro/detemir or using an insulin pump will be converted to lispro/glargine or
      lispro/detemir (respectively) using equivalent insulin units, then proceed to Visit 2 (Week
      -1) after 1 week on the new regimen. At Visit 2 (Week -1), patients will receive the CGM and
      be trained on its use. Patients will also have their first Mixed Meal Tolerance Test (MMTT)
      during Visit 2 (Week -1) accompanied by monitoring of blood ketones pre- and post-ingestion.
      CGM and MMTT will be repeated at Visits 9 (Week 12) and 14 (Week 25). A diary, glucose meter,
      and supplies will also be provided at Visit 2 (Week -1). Patients will be instructed on how
      to perform self-monitored blood glucose measurements (SMBG). During Visit 3 (Week 0),
      eligible patients will be randomized by IWRS to either treatment arm (Test Group or Control
      Group) and baseline data will be collected. All visits will include progress reviews and
      safety procedures. Safety hematology/chemistry/ urinalysis at Visits 2 (Week -1), 10 (Week
      13), 14 (Week 25) and 16 (Week 27) will include liver enzymes. At Visits 6 (Week 5) and 12
      (Week 19), liver enzymes will be the only chemistry safety tests performed. The only
      chemistry safety tests performed at Visits 2 (Week -1), 9 (Week 12), and 14 (Week 25) will be
      blood ketones; these will be measured at baseline and 3 hours after the MMTT. HbA1c will be
      measured at Visits 3 (Week 0), 4 (Week 1), 7 (Week 7), 10 (Week 13), 12 (Week 19), and 15
      (Week 26). Fasting blood glucose will be measured at Visits 3 (Week 0), 10 (Week 13), and 15
      (Week 26). An in-clinic urine pregnancy test will be performed at all visits for women of
      childbearing potential. MRI will be performed at Visits 3 (Week 0) and 14 (Week 25) for
      approximately 20% of patients in each treatment arm. MRI may also be performed on a
      case-by-case basis in the event of abnormal liver enzyme results. Patients will receive
      weekly telephone calls from the PI or a designee to discuss insulin dosing and titration.

      FOLLOW-UP Visit 16 (Week 27) is a safety follow-up visit which will include a physical exam.
      Safety hematology/chemistry/ urinalysis (including liver enzymes) will include a urine
      pregnancy test for women of childbearing potential.

      Concomitant medications, vital signs, and adverse events will be recorded throughout the
      entire study period.
    

Intervention name(s): HDV Insulin Lispro; Insulin LISPRO
Intervention type(s): Drug; Drug
Intervention description(s): HDV Insulin Lispro: ~1% of the Insulin Lispro is bound to HDV (Hepatocyte Directed Vesicle); Insulin Lispro: no bound insulin
Other intervention name(s): HDV Humalog; Humalog
Intervention MeSH terms: Insulin; Insulin, Globin Zinc; Insulin Lispro
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment