Clinical trial NCT02735044: Comparison of the Safety and Efficacy of HOE901-U300 With Lantus in Children and Adolescents With Type 1 Diabetes Mellitus
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 1 Diabetes Mellitus
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2016-04-12
Enrollment: 463
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Change From Baseline in HbA1c to Month 6
timeFrame: Baseline to Month 6
Secondary outcomes:
measure: Change From Baseline in Fasting Plasma Glucose (FPG) to Month 6
timeFrame: Baseline to Month 6
measure: Percentage of Participants With HbA1c Values of <7.5% at Month 6
timeFrame: Month 6
measure: 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
timeFrame: upto Month 6
measure: Percentage of Participants With FPG of <=130 mg/dL (7.2 mmol/L) at Month 6
timeFrame: Month 6
measure: 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
timeFrame: upto Month 6
measure: Change From Baseline in 24-Hour Mean Plasma Glucose Based on 8-point SMPG Profiles to Month 6
timeFrame: Baseline to Month 6
measure: Change From Baseline in Variability of 24-Hour Mean Plasma Glucose Based on 8-point SMPG Profiles at Month 6
timeFrame: Baseline, Month 6
measure: Change From Baseline to Month 6 in 8-Point SMPG Profile Per Time Point
timeFrame: Baseline to Month 6
measure: 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
timeFrame: Month 12
measure: Percentage of Participants With Any Hyperglycemia With Ketosis at Month 12
timeFrame: Month 12
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Investigational Site Number 8400008
state: Arizona
city: Atlanta
country: United States
facility: Investigational Site Number 8400037
state: Georgia
city: Indianapolis
country: United States
facility: Investigational Site Number 8400032
state: Indiana
city: Buffalo
country: United States
facility: Investigational Site Number 8400015
state: New York
city: Chapel Hill
country: United States
facility: Investigational Site Number 8400016
state: North Carolina
city: Morehead City
country: United States
facility: Investigational Site Number 8400035
state: North Carolina
city: Oklahoma City
country: United States
facility: Investigational Site Number 8400038
state: Oklahoma
city: Philadelphia
country: United States
facility: Investigational Site Number 8400030
state: Pennsylvania
city: Rapid City
country: United States
facility: Investigational Site Number 8400010
state: South Dakota
city: Dallas
country: United States
facility: Investigational Site Number 8400005
state: Texas
city: Dallas
country: United States
facility: Investigational Site Number 8400021
state: Texas
city: Lufkin
country: United States
facility: Investigational Site Number 8400029
state: Texas
city: Seattle
country: United States
facility: Investigational Site Number 8400034
state: Washington
city: Caba
country: Argentina
facility: Investigational Site Number 0320003
city: Caba
country: Argentina
facility: Investigational Site Number 0320001
city: Capital Federal
country: Argentina
facility: Investigational Site Number 0320004
city: Capital Federal
country: Argentina
facility: Investigational Site Number 0320002
city: Mendoza
country: Argentina
facility: Investigational Site Number 0320006
city: Salta
country: Argentina
facility: Investigational Site Number 0320005
city: San Miguel De Tucuman
country: Argentina
facility: Investigational Site Number 0320007
city: Curitiba
country: Brazil
facility: Investigational Site Number 0760005
city: Fortaleza
country: Brazil
facility: Investigational Site Number 0760006
city: Fortaleza
country: Brazil
facility: Investigational Site Number 0760004
city: Porto Alegre
country: Brazil
facility: Investigational Site Number 0760003
city: Sao Paulo
country: Brazil
facility: Investigational Site Number 0760001
city: Sao Paulo
country: Brazil
facility: Investigational Site Number 0760002
city: Plovdiv
country: Bulgaria
facility: Investigational Site Number 1000001
city: Sofia
country: Bulgaria
facility: Investigational Site Number 1000005
city: Varna
country: Bulgaria
facility: Investigational Site Number 1000004
city: Halifax
country: Canada
facility: Investigational Site Number 1240003
city: Montreal
country: Canada
facility: Investigational Site Number 1240002
city: Montreal
country: Canada
facility: Investigational Site Number 1240005
city: Sherbrooke
country: Canada
facility: Investigational Site Number 1240006
city: Santiago
country: Chile
facility: Investigational Site Number 1520002
city: Santiago
country: Chile
facility: Investigational Site Number 1520004
city: Santiago
country: Chile
facility: Investigational Site Number 1520006
city: Temuco
country: Chile
facility: Investigational Site Number 1520007
city: Viña Del Mar
country: Chile
facility: Investigational Site Number 1520003
city: Hradec Kralove
country: Czechia
facility: Investigational Site Number 2030003
city: Ostrava - Poruba
country: Czechia
facility: Investigational Site Number 2030005
city: Praha 5 - Motol
country: Czechia
facility: Investigational Site Number 2030001
city: Herlev
country: Denmark
facility: Investigational Site Number 2080001
city: Montpellier
country: France
facility: Investigational Site Number 2500003
city: Toulouse
country: France
facility: Investigational Site Number 2500002
city: Hannover
country: Germany
facility: Investigational Site Number 2760002
city: Heidelberg
country: Germany
facility: Investigational Site Number 2760001
city: Leipzig
country: Germany
facility: Investigational Site Number 2760004
city: Münster
country: Germany
facility: Investigational Site Number 2760003
city: Budapest
country: Hungary
facility: Investigational Site Number 3480001
city: Budapest
country: Hungary
facility: Investigational Site Number 3480004
city: Budapest
country: Hungary
facility: Investigational Site Number 3480003
city: Gyula
country: Hungary
facility: Investigational Site Number 3480005
city: Miskolc
country: Hungary
facility: Investigational Site Number 3480002
city: Pécs
country: Hungary
facility: Investigational Site Number 3480006
city: Székesfehérvár
country: Hungary
facility: Investigational Site Number 3480007
city: Beer Sheva
country: Israel
facility: Investigational Site Number 3760003
city: Haifa
country: Israel
facility: Investigational Site Number 3760001
city: Holon
country: Israel
facility: Investigational Site Number 3760006
city: Petach Tikva
country: Israel
facility: Investigational Site Number 3760002
city: Firenze
country: Italy
facility: Investigational Site Number 3800001
city: Roma
country: Italy
facility: Investigational Site Number 3800005
city: Torino
country: Italy
facility: Investigational Site Number 3800004
city: Varese
country: Italy
facility: Investigational Site Number 3800006
city: Verona
country: Italy
facility: Investigational Site Number 3800003
city: Chiyoda-Ku
country: Japan
facility: Investigational Site Number 3920006
city: Fukuoka-Shi
country: Japan
facility: Investigational Site Number 3920002
city: Hiroshima-Shi
country: Japan
facility: Investigational Site Number 3920003
city: Kobe-Shi
country: Japan
facility: Investigational Site Number 3920007
city: Osaka-Shi
country: Japan
facility: Investigational Site Number 3920005
city: Shinjuku-Ku
country: Japan
facility: Investigational Site Number 3920004
city: Daugavpils
country: Latvia
facility: Investigational Site Number 4280002
city: Rīga
country: Latvia
facility: Investigational Site Number 4280001
city: Durango
country: Mexico
facility: Investigational Site Number 4840003
city: Monterrey
country: Mexico
facility: Investigational Site Number 4840001
city: México
country: Mexico
facility: Investigational Site Number 4840004
city: Puebla
country: Mexico
facility: Investigational Site Number 4840002
city: Veracruz
country: Mexico
facility: Investigational Site Number 4840005
city: Skopje
country: North Macedonia
facility: Investigational Site Number 8070001
city: Bielsko-Biala
country: Poland
facility: Investigational Site Number 6160005
city: Gdansk
country: Poland
facility: Investigational Site Number 6160001
city: Szczecin
country: Poland
facility: Investigational Site Number 6160006
city: Warszawa
country: Poland
facility: Investigational Site Number 6160007
city: Warszawa
country: Poland
facility: Investigational Site Number 6160004
city: Warszawa
country: Poland
facility: Investigational Site Number 6160003
city: Bucharest
country: Romania
facility: Investigational Site Number 6420005
city: Constanta
country: Romania
facility: Investigational Site Number 6420007
city: Craiova
country: Romania
facility: Investigational Site Number 6420004
city: Sibiu
country: Romania
facility: Investigational Site Number 6420006
city: Timisoara
country: Romania
facility: Investigational Site Number 6420003
city: Moscow
country: Russian Federation
facility: Investigational Site Number 6430001
city: Smolensk
country: Russian Federation
facility: Investigational Site Number 6430004
city: St-Petersburg
country: Russian Federation
facility: Investigational Site Number 6430002
city: Ufa
country: Russian Federation
facility: Investigational Site Number 6430003
city: Belgrade
country: Serbia
facility: Investigational Site Number 6880002
city: Belgrade
country: Serbia
facility: Investigational Site Number 6880003
city: Nis
country: Serbia
facility: Investigational Site Number 6880004
city: Barcelona
country: Spain
facility: Investigational Site Number 7240005
city: Barcelona
country: Spain
facility: Investigational Site Number 7240002
city: Esplugues De Llobregat
country: Spain
facility: Investigational Site Number 7240003
city: Sabadell
country: Spain
facility: Investigational Site Number 7240004
city: Santa Cruz De Tenerife
country: Spain
facility: Investigational Site Number 7240006
city: Vitoria
country: Spain
facility: Investigational Site Number 7240001
city: Stockholm
country: Sweden
facility: Investigational Site Number 7520002
city: Doncaster
country: United Kingdom
facility: Investigational Site Number 8260005
city: Ipswich
country: United Kingdom
facility: Investigational Site Number 8260001
city: Kettering
country: United Kingdom
facility: Investigational Site Number 8260004
city: Salisbury
country: United Kingdom
facility: Investigational Site Number 8260002
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Danne T, Tamborlane WV, Malievsky OA, Franco DR, Kawamura T, Demissie M, Niemoeller E, Goyeau H, Wardecki M, Battelino T. Efficacy and Safety of Insulin Glargine 300 Units/mL (Gla-300) Versus Insulin Glargine 100 Units/mL (Gla-100) in Children and Adolescents (6-17 years) With Type 1 Diabetes: Results of the EDITION JUNIOR Randomized Controlled Trial. Diabetes Care. 2020 Jul;43(7):1512-1519. doi: 10.2337/dc19-1926. Epub 2020 May 19.