Comparison of the Safety and Efficacy of HOE901-U300 With... | NCT02735044

NCT02735044

ID	Type	Description	Link
2015-002084-42	EudraCT Number
U1111-1168-4546	Other Identifier	UTN

Status Module

Oversight Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
HOE901-U300	Experimental	HOE901-U300 (Insulin glargine 300 Units/milliliter [U/mL]) Subcutaneous(SC) injection once daily for 12 months.	Drug: Insulin glargine,300 U/mL Drug: Background therapy
Lantus	Active Comparator	Lantus (Insulin glargine 100 U/mL) SC injection once daily for 12 months.	Drug: Insulin glargine (100 units /mL) Drug: Background therapy

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Insulin glargine,300 U/mL	Drug	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])

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in HbA1c 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.	Baseline to Month 6

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in Fasting Plasma Glucose (FPG) 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.	Baseline to Month 6

Eligibility Module

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.

Name	Affiliation	Role
Clinical Sciences & Operations	Sanofi	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Investigational Site Number 8400008		Tucson	Arizona	85724	United States
Investigational Site Number 8400037

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
32430458	Derived	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.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	HOE901-U300	Insulin glargine 300 Units/milliliter (U/mL) subcutaneous (SC) injection once daily in the morning or evening for 12 months.
FG001	Lantus	Insulin glargine 100 U/mL SC injection once daily in the morning or evening for 12 months.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Aug 23, 2016	May 29, 2019

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	OG000-0.399± 0.063 OG001-0.402± 0.064

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Analysis was performed using ANCOVA models which included the treatment group, the randomization stratum of age group at screening visit (<12 years and >=12 years), and the continuous fixed covariates of the baseline HbA1c value.					LS Mean difference	0.004	Standard Error of the Mean	0.090	2-Sided	95	-0.172	0.179					Non-Inferiority	Non-inferiority of HOE901-U300 versus Lantus was demonstrated if the upper bound of the two-sided 95% confidence interval (CI) for the difference in the mean change in HbA1c from baseline to month 6 was <0.3%.

Secondary

Change From Baseline in Fasting Plasma Glucose (FPG) 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.

Analysis was performed on ITT population. Here, 'Overall number of participants analyzed' signified number of participants with available data for the outcome measure.

Posted

Least Squares Mean

Standard Error

millimole per liter (mmol/L)

Baseline to Month 6

ID	Title	Description
OG000	HOE901-U300	Insulin glargine 300 U/mL SC injection once daily in the morning or evening for 12 months.
OG001	Lantus	Insulin glargine 100 U/mL SC injection once daily in the morning or evening for 12 months.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants With HbA1c Values of <7.5% at 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).

Analysis was performed on ITT population.

Posted

Number

percentage of participants

Month 6

ID	Title	Description
OG000	HOE901-U300	Insulin glargine 300 U/mL SC injection once daily in the morning or evening for 12 months.
OG001	Lantus	Insulin glargine 100 U/mL SC injection once daily in the morning or evening for 12 months.

Units	Counts
Participants	OG000

Secondary

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

Analysis was performed on ITT population.

Posted

Number

percentage of participants

upto Month 6

ID	Title	Description
OG000	HOE901-U300	Insulin glargine 300 U/mL SC injection once daily in the morning or evening for 12 months.
OG001	Lantus	Insulin glargine 100 U/mL SC injection once daily in the morning or evening for 12 months.

Units	Counts
Participants

Secondary

Percentage of Participants With FPG of <=130 mg/dL (7.2 mmol/L) at 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).

Analysis was performed on ITT population.

Posted

Number

percentage of participants

Month 6

ID	Title	Description
OG000	HOE901-U300	Insulin glargine 300 U/mL SC injection once daily in the morning or evening for 12 months.
OG001	Lantus	Insulin glargine 100 U/mL SC injection once daily in the morning or evening for 12 months.

Units	Counts
Participants	OG000

Secondary

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

Analysis was performed on ITT population.

Posted

Number

percentage of participants

upto Month 6

ID	Title	Description
OG000	HOE901-U300	Insulin glargine 300 U/mL SC injection once daily in the morning or evening for 12 months.
OG001	Lantus	Insulin glargine 100 U/mL SC injection once daily in the morning or evening for 12 months.

Units	Counts
Participants

Secondary

Change From Baseline in 24-Hour Mean Plasma Glucose Based on 8-point SMPG Profiles 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.

Analysis was performed on ITT population. Here, 'Overall number of participants analyzed' signified number of participants with available data for the outcome measure.

Posted

Least Squares Mean

Standard Error

mmol/L

Baseline to Month 6

ID	Title	Description
OG000	HOE901-U300	Insulin glargine 300 U/mL SC injection once daily in the morning or evening for 12 months.
OG001	Lantus	Insulin glargine 100 U/mL SC injection once daily in the morning or evening for 12 months.

Units	Counts
Participants

Secondary

Change From Baseline in Variability of 24-Hour Mean Plasma Glucose Based on 8-point SMPG Profiles at 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).

Analysis was performed on ITT population. Here, 'Overall number of participants analyzed' signified number of participants with available data for the outcome measure.

Posted

Least Squares Mean

Standard Error

percentage of mean variability

Baseline, Month 6

ID	Title	Description
OG000	HOE901-U300	Insulin glargine 300 U/mL SC injection once daily in the morning or evening for 12 months.
OG001	Lantus	Insulin glargine 100 U/mL SC injection once daily in the morning or evening for 12 months.

Units

Secondary

Change From Baseline to Month 6 in 8-Point SMPG Profile Per Time Point

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.

Analysis was performed on ITT population. Here, 'number analyzed' = participants with available data for each specified category.

Posted

Mean

Standard Deviation

mmol/L

Baseline to Month 6

ID	Title	Description
OG000	HOE901-U300	Insulin glargine 300 U/mL SC injection once daily in the morning or evening for 12 months.
OG001	Lantus	Insulin glargine 100 U/mL SC injection once daily in the morning or evening for 12 months.

Units	Counts
Participants	OG000

Secondary

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

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.

Analysis was performed on the safety population which included all randomized participants who actually received who received at least 1 dose or part of a dose of IMP, and was analyzed according to treatment received.

Posted

Number

percentage of participants

Month 12

ID	Title	Description
OG000	HOE901-U300	Insulin glargine 300 U/mL SC injection once daily in the morning or evening for 12 months.
OG001

Secondary

Percentage of Participants With Any Hyperglycemia With Ketosis at 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.

Analysis was performed on the safety population.

Posted

Number

percentage of participants

Month 12

ID	Title	Description
OG000	HOE901-U300	Insulin glargine 300 U/mL SC injection once daily in the morning or evening for 12 months.
OG001	Lantus	Insulin glargine 100 U/mL SC injection once daily in the morning or evening for 12 months.

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Adrenal Insufficiency	Endocrine disorders	MedDra 21.1	Systematic Assessment	EG0000 events0 affected233 at risk EG0011 events1 affected228 at risk
Appendicitis	Infections and infestations	MedDra 21.1	Systematic Assessment	EG0001 events1 affected233 at risk EG0012 events2 affected228 at risk
Gastroenteritis	Infections and infestations	MedDra 21.1	Systematic Assessment	EG0001 events1 affected233 at risk EG0011 events1 affected228 at risk
Gastroenteritis Viral	Infections and infestations	MedDra 21.1	Systematic Assessment	EG0001 events1 affected233 at risk EG0010 events0 affected228 at risk
Meningococcal Infection	Infections and infestations	MedDra 21.1	Systematic Assessment	EG0000 events0 affected233 at risk EG0011 events1 affected228 at risk
Septic Shock	Infections and infestations	MedDra 21.1	Systematic Assessment	EG0000 events0 affected233 at risk EG0011 events1 affected228 at risk
Tonsillitis	Infections and infestations	MedDra 21.1	Systematic Assessment	EG0000 events0 affected233 at risk EG0011 events1 affected228 at risk
Urinary Tract Infection	Infections and infestations	MedDra 21.1	Systematic Assessment	EG0001 events1 affected233 at risk EG0011 events1 affected228 at risk
Vulvitis	Infections and infestations	MedDra 21.1	Systematic Assessment	EG0000 events0 affected233 at risk EG0011 events1 affected228 at risk
Accidental Overdose	Injury, poisoning and procedural complications	MedDra 21.1	Systematic Assessment	EG0001 events1 affected233 at risk EG0011 events1 affected228 at risk
Electric Shock	Injury, poisoning and procedural complications	MedDra 21.1	Systematic Assessment	EG0000 events0 affected233 at risk EG0011 events1 affected228 at risk
Fall	Injury, poisoning and procedural complications	MedDra 21.1	Systematic Assessment	EG0001 events1 affected233 at risk EG0010 events0 affected228 at risk
Radius Fracture	Injury, poisoning and procedural complications	MedDra 21.1	Systematic Assessment	EG0001 events1 affected233 at risk EG0010 events0 affected228 at risk
Rib Fracture	Injury, poisoning and procedural complications	MedDra 21.1	Systematic Assessment	EG0001 events1 affected233 at risk EG0010 events0 affected228 at risk
Upper Limb Fracture	Injury, poisoning and procedural complications	MedDra 21.1	Systematic Assessment	EG0001 events1 affected233 at risk EG0010 events0 affected228 at risk
Alanine Aminotransferase Increased	Investigations	MedDra 21.1	Systematic Assessment	EG0003 events3 affected233 at risk EG0011 events1 affected228 at risk
Diabetes Mellitus Inadequate Control	Metabolism and nutrition disorders	MedDra 21.1	Systematic Assessment	EG0002 events2 affected233 at risk EG0012 events2 affected228 at risk
Diabetic Ketoacidosis	Metabolism and nutrition disorders	MedDra 21.1	Systematic Assessment	EG0005 events5 affected233 at risk EG0016 events6 affected228 at risk
Diabetic Metabolic Decompensation	Metabolism and nutrition disorders	MedDra 21.1	Systematic Assessment	EG0001 events1 affected233 at risk EG0010 events0 affected228 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDra 21.1	Systematic Assessment	EG0001 events1 affected233 at risk EG0010 events0 affected228 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDra 21.1	Systematic Assessment	EG0002 events2 affected233 at risk EG0010 events0 affected228 at risk
Ketosis	Metabolism and nutrition disorders	MedDra 21.1	Systematic Assessment	EG0001 events1 affected233 at risk EG0010 events0 affected228 at risk
Autonomic Nervous System Imbalance	Nervous system disorders	MedDra 21.1	Systematic Assessment	EG0001 events1 affected233 at risk EG0010 events0 affected228 at risk
Epilepsy	Nervous system disorders	MedDra 21.1	Systematic Assessment	EG0000 events0 affected233 at risk EG0011 events1 affected228 at risk
Hypoglycaemic Coma	Nervous system disorders	MedDra 21.1	Systematic Assessment	EG0001 events1 affected233 at risk EG0010 events0 affected228 at risk
Hypoglycaemic Seizure	Nervous system disorders	MedDra 21.1	Systematic Assessment	EG00011 events8 affected233 at risk EG00110 events10 affected228 at risk
Hypoglycaemic Unconsciousness	Nervous system disorders	MedDra 21.1	Systematic Assessment	EG00010 events6 affected233 at risk EG00111 events10 affected228 at risk
Seizure	Nervous system disorders	MedDra 21.1	Systematic Assessment	EG0001 events1 affected233 at risk EG0010 events0 affected228 at risk
Syncope	Nervous system disorders	MedDra 21.1	Systematic Assessment	EG0001 events1 affected233 at risk EG0010 events0 affected228 at risk
Anembryonic Gestation	Pregnancy, puerperium and perinatal conditions	MedDra 21.1	Systematic Assessment	EG0001 events1 affected233 at risk EG0010 events0 affected228 at risk
Completed Suicide	Psychiatric disorders	MedDra 21.1	Systematic Assessment	EG0001 events1 affected233 at risk EG0010 events0 affected228 at risk
Confusional State	Psychiatric disorders	MedDra 21.1	Systematic Assessment	EG0000 events0 affected233 at risk EG0011 events1 affected228 at risk
Testicular Torsion	Reproductive system and breast disorders	MedDra 21.1	Systematic Assessment	EG0000 events0 affected233 at risk EG0011 events1 affected228 at risk
Dermal Cyst	Skin and subcutaneous tissue disorders	MedDra 21.1	Systematic Assessment	EG0001 events1 affected233 at risk EG0010 events0 affected228 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Vomiting	Gastrointestinal disorders	MedDra 21.1	Systematic Assessment	EG00020 events14 affected233 at risk EG00110 events9 affected228 at risk
Gastroenteritis	Infections and infestations	MedDra 21.1	Systematic Assessment	EG00014 events12 affected233 at risk EG00114 events10 affected228 at risk
Influenza	Infections and infestations	MedDra 21.1	Systematic Assessment	EG00017 events14 affected233 at risk EG00125 events19 affected228 at risk
Nasopharyngitis	Infections and infestations	MedDra 21.1	Systematic Assessment	EG00057 events37 affected233 at risk EG00160 events39 affected228 at risk
Pharyngitis	Infections and infestations	MedDra 21.1	Systematic Assessment	EG00018 events14 affected233 at risk EG00129 events22 affected228 at risk
Upper Respiratory Tract Infection	Infections and infestations	MedDra 21.1	Systematic Assessment	EG00028 events20 affected233 at risk EG00121 events18 affected228 at risk
Ketosis	Metabolism and nutrition disorders	MedDra 21.1	Systematic Assessment	EG00050 events19 affected233 at risk EG00152 events30 affected228 at risk
Overweight	Metabolism and nutrition disorders	MedDra 21.1	Systematic Assessment	EG0002 events2 affected233 at risk EG00113 events13 affected228 at risk
Headache	Nervous system disorders	MedDra 21.1	Systematic Assessment	EG00038 events19 affected233 at risk EG00123 events15 affected228 at risk
Oropharyngeal Pain	Respiratory, thoracic and mediastinal disorders	MedDra 21.1	Systematic Assessment	EG00017 events15 affected233 at risk EG0017 events7 affected228 at risk

ID	Term
D003920	Diabetes Mellitus
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases
D001327	Autoimmune Diseases
D007154	Immune System Diseases

ID	Term
D049528	Insulin, Long-Acting
D061385	Insulins
D010187	Pancreatic Hormones
D036361	Peptide Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins

ID	Title	Description
BG000	HOE901-U300	Insulin glargine 300 U/mL SC injection once daily in the morning or evening for 12 months.
BG001	Lantus	Insulin glargine 100 U/mL SC injection once daily in the morning or evening for 12 months.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	HOE901-U300	Insulin glargine 300 U/mL SC injection once daily in the morning or evening for 12 months.	1	233	35	233	105	233
EG001	Lantus	Insulin glargine 100 U/mL SC injection once daily in the morning or evening for 12 months.	0	228	31	228	118	228