Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.

Comparison of the Safety and Efficacy of HOE901-U300 With Lantus in Children and Adolescents With Type 1 Diabetes Mellitus (EDITION JUNIOR)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02735044
Recruitment Status : Completed
First Posted : April 12, 2016
Results First Posted : June 19, 2019
Last Update Posted : July 30, 2019
Sponsor:
Information provided by (Responsible Party):
Sanofi

Brief Summary:

Primary Objective:

To compare the efficacy of a new formulation of insulin glargine (HOE901-U300) to Lantus in terms of change of HbA1c from baseline to endpoint (month 6) in children and adolescents with type 1 diabetes mellitus.

.

Secondary Objectives:

To compare HOE901-U300 and Lantus in terms of:

  • Percentage of participants reaching target HbA1c and fasting plasma glucose (FPG).
  • To assess the safety of HOE901-U300 including analysis of events of hypoglycemia, events of hyperglycemia with ketosis, and development of anti-insulin-antibodies.

Condition or disease Intervention/treatment Phase
Type 1 Diabetes Mellitus Drug: Insulin glargine,300 U/mL Drug: Insulin glargine (100 units /mL) Drug: Background therapy Phase 3

Detailed Description:
The study duration per participant was approximately 58 weeks that consisted of a 2 week screening period, a main 6-month comparative efficacy and safety treatment period, a 6-month comparative safety extension period, and a 4-week post treatment follow up period.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 463 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 6-Month, Multicenter, Randomized, Open-label, 2-Arm, Parallel-group Study Comparing the Efficacy and Safety of a New Formulation of Insulin Glargine and Lantus® Injected Once Daily in Children and Adolescents Age 6 - 17 Years With Type 1 Diabetes Mellitus With a 6-month Safety Extension Period
Actual Study Start Date : April 14, 2016
Actual Primary Completion Date : May 31, 2018
Actual Study Completion Date : December 20, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1

Arm Intervention/treatment
Experimental: HOE901-U300
HOE901-U300 (Insulin glargine 300 Units/milliliter [U/mL]) Subcutaneous(SC) injection once daily for 12 months.
Drug: Insulin glargine,300 U/mL
Subcutaneous injection in the morning or evening using a prefilled pen. Dose titration to achieve fasting self-monitored plasma glucose (SMPG) from 90 to 130 milligram/deciliter (mg/dL) (5.0 to 7.2 millimol per liter [mmol/L])
Other Name: Toujeo ®

Drug: Background therapy
Fast-acting mealtime insulin analogs

Active Comparator: Lantus
Lantus (Insulin glargine 100 U/mL) SC injection once daily for 12 months.
Drug: Insulin glargine (100 units /mL)
Subcutaneous injection in the morning or evening using a prefilled pen. Dose titration to achieve fasting SMPG from 90 to 130 mg/dL (5.0 to 7.2 mmol/L)

Drug: Background therapy
Fast-acting mealtime insulin analogs




Primary Outcome Measures :
  1. Change From Baseline in HbA1c to Month 6 [ Time Frame: Baseline to Month 6 ]
    Change in HbA1c was calculated by subtracting baseline value from Month 6 value. Adjusted least-square (LS) means and standard errors (SE) were obtained using analysis of covariance (ANCOVA) after multiple imputations of missing data using post-baseline HbA1c data available on the main 6-month randomized period.


Secondary Outcome Measures :
  1. Change From Baseline in Fasting Plasma Glucose (FPG) to Month 6 [ Time Frame: Baseline to Month 6 ]
    Change in FPG was calculated by subtracting baseline value from Month 6 value. Adjusted LS means and SE were obtained using ANCOVA after multiple imputation to address missing data in the main 6 month randomized period.

  2. Percentage of Participants With HbA1c Values of <7.5% at Month 6 [ Time Frame: Month 6 ]
    Participants without any available HbA1c assessment at month 6 and/or with a premature study discontinuation during the main 6-month randomized period were considered as a failure (non-responders) in the analysis. Analysis was performed using Cochran-Mantel-Haenszel (CMH) method with randomization strata of screening HbA1c (<8.5%; >=8.5%) and randomization strata of age at screening (<12 years, >=12 years).

  3. Percentage of Participants With HbA1c Values of <7.5% Without Any Episode of Severe and/or Documented Self-Monitored Plasma Glucose ([SMPG] <54 mg/dL [3.0 mmol/L]) Symptomatic Hypoglycemia During the Last 3 Months of the Main 6-month Randomized Period [ Time Frame: upto Month 6 ]
    Participants without any available HbA1c assessment at month 6 and/or with a premature study discontinuation during the main 6-month randomized period were considered as a failure (non-responders) in the analysis. Analysis was performed using Cochran-Mantel-Haenszel (CMH) method with randomization strata of screening HbA1c (<8.5%; >=8.5%) and randomization strata of age at screening (<12 years, >=12 years).

  4. Percentage of Participants With FPG of <=130 mg/dL (7.2 mmol/L) at Month 6 [ Time Frame: Month 6 ]
    Participants without any available FPG assessment at month 6 and/or with a premature study discontinuation during the main 6-month randomized period were considered as a failure (non-responders) in the analysis. Analysis was performed using Cochran-Mantel-Haenszel (CMH) method with randomization strata of screening HbA1c (<8.5%; >=8.5%) and randomization strata of age at screening (<12 years, >=12 years).

  5. Percentage of Participants With FPG of <=130 mg/dL (7.2 mmol/L) Without Any Episode of Severe and/or Documented (SMPG <54 mg/dL [3.0 mmol/L]) Symptomatic Hypoglycemia During the Last 3 Months of the Main 6-month Randomized Period [ Time Frame: upto Month 6 ]
    Participants without any available HbA1c assessment at month 6 and/or with a premature study discontinuation during the main 6-month randomized period were considered as a failure (non-responders) in the analysis. Analysis was performed using Cochran-Mantel-Haenszel (CMH) method with randomization strata of screening HbA1c (<8.5%; >=8.5%) and randomization strata of age at screening (<12 years, >=12 years).

  6. Change From Baseline in 24-Hour Mean Plasma Glucose Based on 8-point SMPG Profiles to Month 6 [ Time Frame: Baseline to Month 6 ]
    8-point SMPG profiles were measured at the following 8 points: between 01:00 and 04:00 (clock time) at night, pre-breakfast, 2 hours after breakfast, pre-lunch, 2 hours after lunch, pre-dinner, 2 hours after dinner, and bedtime. Analysis was performed using a ANCOVA model including the fixed categorical effects of treatment group, randomization strata of screening HbA1c (<8.5%; >=8.5%), randomization strata of age at screening (<12 years, >=12 years) and the baseline 24-hour average 8-point profile SMPG.

  7. Change From Baseline in Variability of 24-Hour Mean Plasma Glucose Based on 8-point SMPG Profiles at Month 6 [ Time Frame: Baseline, Month 6 ]
    8-point SMPG profiles were measured at the following 8 points: between 01:00 and 04:00 (clock time) at night, pre-breakfast, 2 hours after breakfast, pre-lunch, 2 hours after lunch, pre-dinner, 2 hours after dinner, and bedtime. Variability was assessed by the coefficient of variation (standard deviation divided by mean) calculated over the 8-point SMPG. Analysis was performed using a ANCOVA model including the fixed categorical effects of treatment group, randomization strata of screening HbA1c (<8.5%; >=8.5%) and randomization strata of age at screening (<12 years, >=12 years).

  8. Change From Baseline to Month 6 in 8-Point SMPG Profile Per Time Point [ Time Frame: Baseline to Month 6 ]
    8-point SMPG profiles were measured for following 8 time points at Baseline and Month 6: between 01:00 and 04:00 (clock time) at night, pre-breakfast, 2 hours after breakfast, pre-lunch, 2 hours after lunch, pre-dinner, 2 hours after dinner, and bedtime.

  9. Percentage of Participants With at Least One Hypoglycemic Events (Any Hypoglycemia, Severe Hypoglycemia, Documented Symptomatic, Probable Symptomatic, Asymptomatic Hypoglycemia, Pseudo-hypoglycemia and Severe and/or Confirmed Hypoglycemia) at Month 12 [ Time Frame: Month 12 ]
    Severe hypoglycemia: an event in which the child/adolescent having altered mental status and cannot assist in their care, is semiconscious or unconscious, or in coma ± convulsions and may require parenteral therapy (glucagon or glucose). Documented symptomatic hypoglycemia: an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of <=70 mg/dL (3.9 mmol/L). Asymptomatic hypoglycemia: an event not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose concentration <=70 mg/dL. Probable symptomatic hypoglycemia: an event during which symptoms of hypoglycemia were not accompanied by plasma glucose determination but was presumably caused by a plasma glucose concentration <=70 mg/dL. Pseudo-hypoglycemia:an event with any of the typical symptoms of hypoglycaemia with plasma glucose concentration >70 mg/dL.

  10. Percentage of Participants With Any Hyperglycemia With Ketosis at Month 12 [ Time Frame: Month 12 ]
    Hyperglycemia with ketosis was defined as SMPG >=252 mg/dL (14 mmol/L) with accompanying self-measured blood ketones >=1.5 mmol/L.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   6 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria :

  • Children and adolescents with type 1 diabetes mellitus (T1DM) for at least 1 year confirmed by typical symptoms at diagnosis and/or by antibody testing [presence of anti-GAD (glutamic acid decarboxylase) or anti-IA2 (islet antigen 2/tyrosine phosphatase) or anti-islet cell antibodies] and/or clinical features (eg, history of ketoacidosis)].
  • Signed written informed consent obtained from parent(s)/legal guardian and written or oral assent obtained from participant.

Exclusion criteria:

  • Age <6 years and >=18 years at randomization.
  • Less than 1 year on insulin treatment prior to screening visit.
  • Less than 6 months on basal plus mealtime insulin and self-monitoring of blood glucose prior to screening visit.
  • Participants using premix insulins in the last 3 months before screening visit or participants using human regular insulin as mealtime insulin in the last 3 months before screening visit.
  • Use of an insulin pump in the last 6 months before screening visit or plans to switch to pump within the next 6 months after screening visit.
  • Any contraindication to use of insulin glargine as defined in the national product label.
  • No willingness to inject insulin glargine (Lantus or HOE901-U300) once daily.
  • HbA1c <7.5% or >11% at screening.
  • Initiation of any glucose-lowering medications in the last 3 months before screening visit.
  • Hospitalization or care in the emergency ward for diabetic ketoacidosis or history of severe hypoglycemia (as defined by need for glucagon or IV glucose) and accompanied by seizure and/or unconsciousness and/or coma in the last 3 months prior to screening visit.
  • Postmenarchal girls not protected by highly-effective method(s) of birth control and/or who were unwilling or unable to be tested for pregnancy. Abstinence from sexual intercourse was considered as an acceptable form of birth control.
  • Pregnant or breast-feeding adolescents, or adolescents who intended to become pregnant during the study period, or who were at risk of getting pregnant due to any psychosocial reason during the study period.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02735044


Locations
Show Show 107 study locations
Sponsors and Collaborators
Sanofi
Investigators
Layout table for investigator information
Study Director: Clinical Sciences & Operations Sanofi
  Study Documents (Full-Text)

Documents provided by Sanofi:
Study Protocol  [PDF] August 23, 2016
Statistical Analysis Plan  [PDF] April 20, 2017


Layout table for additonal information
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT02735044    
Other Study ID Numbers: EFC13957
2015-002084-42 ( EudraCT Number )
U1111-1168-4546 ( Other Identifier: UTN )
First Posted: April 12, 2016    Key Record Dates
Results First Posted: June 19, 2019
Last Update Posted: July 30, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual participant data (IPD) and supporting clinical documents are available for request at clinicalstudydatarequest.com. While making information available we continue to protect the privacy of the participants in our clinical trials and to remove commercially confidential information (CCI). Details on Data Sharing criteria and process for requesting access can be found at this web address: clinicalstudydatarequest.com
Additional relevant MeSH terms:
Layout table for MeSH terms
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Insulin
Insulin, Globin Zinc
Insulin Glargine
Hypoglycemic Agents
Physiological Effects of Drugs