Diabetes Mellitus, Type 1
Conditions
Keywords
Diabetes, Diabetes Type 1, Type 1, Basal, Insulin, Glargine, T1DM, Diabetes Mellitus, Insulin Dependent Diabetes
Brief summary
Primary Objective: •To evaluate equivalence of Gan & Lee Insulin Glargine Injection and Lantus® in terms of immunogenicity Secondary Objective: Immunogenicity: • To evaluate the percentage of subjects with negative anti-insulin antibodies (AIAs) at baseline who develop confirmed positive AIA up to Week 26, the percentage of baseline in AIA titers between treatment groups, the percentage of subjects with confirmed positive AIA who develop any anti-insulin neutralizing antibodies up to visit Week 26, and percentage of subjects who develop confirmed positive AIA up to visit Week 26 of Gan & Lee Insulin Glargine Injection in comparison with that of Lantus®. Safety: •To evaluate the safety of Gan & Lee Insulin Glargine Injection in comparison with that of Lantus®. Efficacy: •To evaluate the efficacy of Gan & Lee Insulin Glargine Injection in comparison with that of Lantus®.
Interventions
BIOLOGICALGan & Lee Insulin Glargine Injection
Route of administration: subcutaneous injection
BIOLOGICALLantus®
Route of administration: subcutaneous injection
Sponsors
Gan and Lee Pharmaceuticals, USA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Subjects who meet the study eligibility criteria will be centrally randomized 1:1 in an open-label fashion to receive either Gan & Lee Insulin Glargine Injection or Lantus® for 26 weeks. Randomization will be stratified by country.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Male or nonpregnant, nonlactating female subjects between the ages of 18 and 75 years, inclusive. 2. Ability to provide written, personally signed, and dated informed consent to participate in the study, in accordance with the ICH GCP Guideline E6 and all applicable regulations, before initiating any study-related procedures. 3. Ability to understand and fully comply with all study procedures and restrictions. 4. Subjects with a confirmed diagnosis of type 1 diabetes mellitus who have been on an approved basal and bolus insulin regimen for at least 6 months (the type or brand of insulin should not have changed in the 6 months before screening). 5. HbA1c ≤ 11.0%. 6. BMI ≥ 19 kg/m2 and ≤ 35 kg/m2. 7. Adherence to a prudent diet and exercise regimen recommended by the medical provider, and willingness to maintain these consistently for the duration of the study. 8. Concomitant medications are allowed, provided that no significant dosing changes are anticipated during the study (see the
Exclusion criteria
below for specific prohibited concomitant medications); for concomitant thyroid medications, subjects must have been on a stable dosage for 90 days before screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment-induced Anti-Insulin Antibody (TI-AIA) | Assessed up to Week 26 | TI-AIA is the Composite of Newly Confirmed Positive AIA or Important-Increase in AIA titer |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects in Each Treatment Group With Negative AIA at Baseline Who Develop Confirmed Positive AIA After Baseline | Assessed up to Week 26 | The number of subjects in each treatment group with negative AIA at baseline who develop confirmed positive AIA after baseline and up to visit Week 26. |
| Number of Subjects in Each Treatment Group With Confirmed Positive AIA at Baseline and at Least a 4-fold Increase in Titers After Baseline. | Up to Week 26 | The number of subjects in each treatment group with confirmed positive AIA at baseline and at least a 4-fold increase in titers after baseline and up to 26 weeks. |
| Mean Change From Baseline in Each Treatment Group in AIA Titers After Baseline | Assessed up to Week 26 | The mean change from baseline in each treatment group in AIA titers after baseline and up to visit Week 26. |
| Glycosylated Hemoglobin HbA1c | Assessed up to Week 26 | The change between baseline (CFB) in HbA1c and at 26 weeks |
| Number of Subjects With Confirmed Positive AIA After Baseline. | Up to Week 26 | The number of subjects in each treatment group with confirmed positive AIA after baseline and up to visit Week 26. |
| Postbaseline FBG Control | Up to Week 26 | The number of subjects who achieve an FBG test result of ≤ 6.0 mmol/L at visit Week 26. |
| HbA1c Control. | Up to Week 26 | The number of subjects who achieve a HbA1c of \< 7.0% at visit Week 26. |
| Number of Subjects With Confirmed Positive AIA After Baseline Who Develop Any Anti-insulin Neutralizing Antibodies After Baseline. | Up to Week 26 | The number of subjects in each treatment group with confirmed positive AIA after baseline and up to visit Week 26 who develop any anti-insulin neutralizing antibodies after baseline and up to visit Week 26. |
Countries
Czechia, Germany, Hungary, Poland, Spain, United States
Participant flow
Recruitment details
Reviewed and approved by each IRB.
Participants by arm
| Arm | Count |
|---|---|
| Gan & Lee Insulin Glargine Injection Gan & Lee Insulin Glargine Injection for subcutaneous injection, 100 U/mL, in the integrated, disposable 3.0-mL pre-filled Gan & Lee injector pen. Subjects randomized to the Gan & Lee Insulin Glargine Injection group will participate in the study for 26 weeks.
Gan & Lee Insulin Glargine Injection: Route of administration: subcutaneous injection | 287 |
| Lantus® Lantus® (insulin glargine injection) solution for subcutaneous injection, 100 U/mL, in the SoloStar® 3.0 mL pre-filled insulin pen. Subjects randomized to the Lantus® group will participate for 26 weeks.
Lantus®: Route of administration: subcutaneous injection | 289 |
| Total | 576 |
Baseline characteristics
| Characteristic | Gan & Lee Insulin Glargine Injection | Total | Lantus® |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 31 Participants | 68 Participants | 37 Participants |
| Age, Categorical Between 18 and 65 years | 256 Participants | 508 Participants | 252 Participants |
| Age, Continuous | 45.7 Years STANDARD_DEVIATION 13.96 | 46.2 Years STANDARD_DEVIATION 14.21 | 46.7 Years STANDARD_DEVIATION 14.46 |
| Anti-Insulin Antibodies (AIA) Missing | 2 Participants | 2 Participants | 0 Participants |
| Anti-Insulin Antibodies (AIA) Negative | 236 Participants | 475 Participants | 239 Participants |
| Anti-Insulin Antibodies (AIA) Nonreportable | 0 Participants | 2 Participants | 2 Participants |
| Anti-Insulin Antibodies (AIA) Positive | 49 Participants | 97 Participants | 48 Participants |
| Anti-Insulin Neutralizing Antibodies (NAbs) Missing | 1 Participants | 2 Participants | 1 Participants |
| Anti-Insulin Neutralizing Antibodies (NAbs) Negative | 44 Participants | 82 Participants | 38 Participants |
| Anti-Insulin Neutralizing Antibodies (NAbs) Not Tested | 236 Participants | 477 Participants | 241 Participants |
| Anti-Insulin Neutralizing Antibodies (NAbs) Positive | 6 Participants | 15 Participants | 9 Participants |
| Body Mass Index (BMI) | 27.01 kg/m2 STANDARD_DEVIATION 3.875 | 27.06 kg/m2 STANDARD_DEVIATION 4.058 | 27.11 kg/m2 STANDARD_DEVIATION 4.237 |
| Duration of Diabetes | 20.2 Years STANDARD_DEVIATION 13.88 | 21.0 Years STANDARD_DEVIATION 13.92 | 21.7 Years STANDARD_DEVIATION 13.95 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 23 Participants | 39 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 259 Participants | 531 Participants | 272 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 6 Participants | 1 Participants |
| Glycosylated Hemoglobin (HbA1c) | 8.11 HbA1c (%) STANDARD_DEVIATION 1.229 | 8.10 HbA1c (%) STANDARD_DEVIATION 1.247 | 8.08 HbA1c (%) STANDARD_DEVIATION 1.267 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 13 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants | 27 Participants | 14 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) White | 262 Participants | 527 Participants | 265 Participants |
| Region of Enrollment Czechia | 24 participants | 49 participants | 25 participants |
| Region of Enrollment Germany | 29 participants | 57 participants | 28 participants |
| Region of Enrollment Hungary | 20 participants | 41 participants | 21 participants |
| Region of Enrollment Poland | 37 participants | 74 participants | 37 participants |
| Region of Enrollment Spain | 26 participants | 54 participants | 28 participants |
| Region of Enrollment United States | 151 participants | 301 participants | 150 participants |
| Sex: Female, Male Female | 103 Participants | 215 Participants | 112 Participants |
| Sex: Female, Male Male | 184 Participants | 361 Participants | 177 Participants |
| Thyroid Disease Absence | 243 Participants | 453 Participants | 210 Participants |
| Thyroid Disease Hyperthyroidism | 1 Participants | 6 Participants | 5 Participants |
| Thyroid Disease Hypothyroidism | 32 Participants | 84 Participants | 52 Participants |
| Thyroid Disease Other | 6 Participants | 24 Participants | 18 Participants |
| Thyroid Disease Presence | 44 Participants | 123 Participants | 79 Participants |
| Thyroid Disease Structural abnormality | 5 Participants | 9 Participants | 4 Participants |
| Thyroid Disease Thyroid Cancer | 0 Participants | 0 Participants | 0 Participants |
| Weight | 80.901 kg STANDARD_DEVIATION 13.4277 | 81.226 kg STANDARD_DEVIATION 14.9829 | 81.548 kg STANDARD_DEVIATION 16.3993 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 287 | 1 / 289 |
| other Total, other adverse events | 160 / 287 | 161 / 289 |
| serious Total, serious adverse events | 10 / 287 | 14 / 289 |
Outcome results
Primary
Treatment-induced Anti-Insulin Antibody (TI-AIA)
TI-AIA is the Composite of Newly Confirmed Positive AIA or Important-Increase in AIA titer
Time frame: Assessed up to Week 26
Population: The Safety Analysis Set (SS) was comprised of all subjects whose treatment assignment was randomly assigned who received any of the study treatment, even a partial dose, and had non-missing values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gan & Lee Insulin Glargine Injection | Treatment-induced Anti-Insulin Antibody (TI-AIA) | 4.8 Titers | Standard Deviation 88.88 |
| Lantus® | Treatment-induced Anti-Insulin Antibody (TI-AIA) | 42.5 Titers | Standard Deviation 332.9 |
Comparison: This is a two-arm study.90% CI: [-5.4, 6.5]
Secondary
Glycosylated Hemoglobin HbA1c
The change between baseline (CFB) in HbA1c and at 26 weeks
Time frame: Assessed up to Week 26
Population: The Full Analysis Set (FAS) was comprised of all subjects whose treatment assignment was randomly assigned with non-missing baseline values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Gan & Lee Insulin Glargine Injection | Glycosylated Hemoglobin HbA1c | -0.08 Percent of total hemoglobin | Standard Error 0.072 |
| Lantus® | Glycosylated Hemoglobin HbA1c | 0.00 Percent of total hemoglobin | Standard Error 0.061 |
Secondary
HbA1c Control.
The number of subjects who achieve a HbA1c of \< 7.0% at visit Week 26.
Time frame: Up to Week 26
Population: HbA1c control (HbA1c \< 7.0%).
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Gan & Lee Insulin Glargine Injection | HbA1c Control. | Lack of Postbaseline HbA1c Control | 241 Participants |
| Gan & Lee Insulin Glargine Injection | HbA1c Control. | Sufficient Postbaseline HbA1c Control | 46 Participants |
| Lantus® | HbA1c Control. | Lack of Postbaseline HbA1c Control | 245 Participants |
| Lantus® | HbA1c Control. | Sufficient Postbaseline HbA1c Control | 44 Participants |
Secondary
Mean Change From Baseline in Each Treatment Group in AIA Titers After Baseline
The mean change from baseline in each treatment group in AIA titers after baseline and up to visit Week 26.
Time frame: Assessed up to Week 26
Population: Subjects with Confirmed Positive Anti-Insulin Antibodies at Baseline with non-missing AIA titer values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gan & Lee Insulin Glargine Injection | Mean Change From Baseline in Each Treatment Group in AIA Titers After Baseline | 4.8 Titers | Standard Deviation 88.88 |
| Lantus® | Mean Change From Baseline in Each Treatment Group in AIA Titers After Baseline | -42.5 Titers | Standard Deviation 332.9 |
Secondary
Number of Subjects in Each Treatment Group With Confirmed Positive AIA at Baseline and at Least a 4-fold Increase in Titers After Baseline.
The number of subjects in each treatment group with confirmed positive AIA at baseline and at least a 4-fold increase in titers after baseline and up to 26 weeks.
Time frame: Up to Week 26
Population: Subset of subjects whose baseline AIA was confirmed positive (n=97).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Gan & Lee Insulin Glargine Injection | Number of Subjects in Each Treatment Group With Confirmed Positive AIA at Baseline and at Least a 4-fold Increase in Titers After Baseline. | 11 Participants |
| Lantus® | Number of Subjects in Each Treatment Group With Confirmed Positive AIA at Baseline and at Least a 4-fold Increase in Titers After Baseline. | 14 Participants |
Secondary
Number of Subjects in Each Treatment Group With Negative AIA at Baseline Who Develop Confirmed Positive AIA After Baseline
The number of subjects in each treatment group with negative AIA at baseline who develop confirmed positive AIA after baseline and up to visit Week 26.
Time frame: Assessed up to Week 26
Population: Subset of subjects whose baseline AIA was negative (n=475).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Gan & Lee Insulin Glargine Injection | Number of Subjects in Each Treatment Group With Negative AIA at Baseline Who Develop Confirmed Positive AIA After Baseline | 63 Participants |
| Lantus® | Number of Subjects in Each Treatment Group With Negative AIA at Baseline Who Develop Confirmed Positive AIA After Baseline | 59 Participants |
Secondary
Number of Subjects With Confirmed Positive AIA After Baseline.
The number of subjects in each treatment group with confirmed positive AIA after baseline and up to visit Week 26.
Time frame: Up to Week 26
Population: Safety Analysis Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Gan & Lee Insulin Glargine Injection | Number of Subjects With Confirmed Positive AIA After Baseline. | 102 Participants |
| Lantus® | Number of Subjects With Confirmed Positive AIA After Baseline. | 103 Participants |
Secondary
Number of Subjects With Confirmed Positive AIA After Baseline Who Develop Any Anti-insulin Neutralizing Antibodies After Baseline.
The number of subjects in each treatment group with confirmed positive AIA after baseline and up to visit Week 26 who develop any anti-insulin neutralizing antibodies after baseline and up to visit Week 26.
Time frame: Up to Week 26
Population: Safety Analysis Set - Subjects with Confirmed Positive AIA after Baseline.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Gan & Lee Insulin Glargine Injection | Number of Subjects With Confirmed Positive AIA After Baseline Who Develop Any Anti-insulin Neutralizing Antibodies After Baseline. | 13 Participants |
| Lantus® | Number of Subjects With Confirmed Positive AIA After Baseline Who Develop Any Anti-insulin Neutralizing Antibodies After Baseline. | 16 Participants |
Secondary
Postbaseline FBG Control
The number of subjects who achieve an FBG test result of ≤ 6.0 mmol/L at visit Week 26.
Time frame: Up to Week 26
Population: FBG control (FBG ≤ 6.0 mmol/L).
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Gan & Lee Insulin Glargine Injection | Postbaseline FBG Control | Lack of Postbaseline FBG control | 248 Participants |
| Gan & Lee Insulin Glargine Injection | Postbaseline FBG Control | Sufficient Postbaseline FBG control | 39 Participants |
| Lantus® | Postbaseline FBG Control | Sufficient Postbaseline FBG control | 42 Participants |
| Lantus® | Postbaseline FBG Control | Lack of Postbaseline FBG control | 247 Participants |