Diabetes Mellitus, Type 2
Conditions
Keywords
Diabetes, Diabetes Type 2, Type 2, Basal, Insulin, Glargine, T2DM, Diabetes Mellitus
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 (AIA) at baseline who develop confirmed positive AIA up to Week 26, the percentage of subjects with at least a 4-fold increase in titers compared to baseline value, mean change from 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 the percentage of subjects in each treatment group with confirmed positive AIA up to visit Week 26 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.
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 2 diabetes mellitus who meet one of the following: 1. If insulin-naïve, subjects should have been on at least 2 approved OAMs for at least 12 weeks before screening, and the clinician has decided to add insulin therapy. 2. If already being treated with a basal and/or bolus insulin, subjects should have been treated with insulin for at least 6 months in addition to at least 1 approved OAM, and must not have changed the type or brand of insulin within 6 months prior to screening. 5. HbA1c values as follows: 1. If insulin-naïve, HbA1c ≤ 11.0%. 2. If previously on a basal insulin regimen, HbA1c ≥ 7.0% and ≤ 11.0%. 6. Body mass index (BMI) ≤ 45 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) is the Primary Endpoint | Baseline to Week 26 | Subjects were classified as experiencing a TI-AIA or not. A TI-AIA is defined as a subject experiencing a newly confirmed positive AIA status, if they were negative at baseline or a 4-fold increase in their titer values if they were positive. The primary outcome measure is summarized as the percent of subjects experiencing a TI-AIA in the group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity - Percentage of Subjects in Each Treatment Group With Negative AIA at Baseline Who Develop Confirmed Positive AIA After Baseline | Baseline to Week 26 | The percentage of subjects in each treatment group with negative AIA at baseline who develop confirmed positive AIA after baseline and up to visit Week 26. |
| Immunogenicity - Percentage of Subjects in Each Treatment Group With Confirmed Positive AIA at Baseline Who Developed at Least a 4-fold Increase in Titers After Baseline | Baseline to Week 26 | The percentage of subjects in each treatment group with confirmed positive AIA at baseline (n=6) who developed an important increase (at least a 4-fold increase in titers after baseline) up to visit Week 26. |
| Immunogenicity - Mean Change From Baseline in Each Treatment Group in AIA Titers After Baseline | Baseline to Week 26 | The mean change from baseline in each treatment group in AIA titers after baseline and up to visit Week 26. |
| CFB in HbA1c to Week 26 | Baseline to Week 26 | Change is HbA1c value at week 26 minus the value at baseline. |
| Immunogenicity - Percentage of Subjects With Confirmed Positive AIA After Baseline | Baseline to Week 26 | The percentage of subjects in each treatment group with confirmed positive AIA after baseline and up to visit Week 26. |
| Efficacy - Postbaseline FBG Control | Baseline to Week 26 | The number and percentage of subjects who achieve an FBG test result of ≤ 8.0 mmol/L (≤ 144.0 mg/dL) at visit Week 26. |
| Efficacy - HbA1c Control | At Week 26 | The number and percentage of subjects who achieve a HbA1c of \< 7.0% at visit Week 26. |
| Immunogenicity - Percentage of Subjects With Confirmed Positive AIA After Baseline Who Develop Any Anti-insulin Neutralizing Antibodies After Baseline | Baseline to Week 26 | The percentage 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
United States
Participant flow
Recruitment details
Reviewed and approved by each IRB.
Pre-assignment details
Inclusion and Exclusion Criteria.
Participants by arm
| Arm | Count |
|---|---|
| Gan & Lee Insulin Glargine Injection Gan & Lee Insulin Glargine Injection solution for subcutaneous injection, 100 U/mL, in the integrated, disposable 3.0 mL prefilled 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 | 284 |
| Lantus® Lantus® solution for subcutaneous injection, 100 U/mL, in the SoloStar® 3.0 mL prefilled insulin pen. Subjects randomized to the Lantus® group will participate for 26 weeks.
Lantus®: Route of administration: subcutaneous injection | 283 |
| Total | 567 |
Baseline characteristics
| Characteristic | Gan & Lee Insulin Glargine Injection | Total | Lantus® |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 121 Participants | 226 Participants | 105 Participants |
| Age, Categorical Between 18 and 65 years | 163 Participants | 341 Participants | 178 Participants |
| AIA result Negative | 252 Participants | 515 Participants | 263 Participants |
| AIA result Nonreportable | 27 Participants | 46 Participants | 19 Participants |
| AIA result Positive | 5 Participants | 6 Participants | 1 Participants |
| Body Mass Index (BMI) ≤45 kg/m^2 | 33.49 kg/m2 STANDARD_DEVIATION 5.589 | 33.54 kg/m2 STANDARD_DEVIATION 5.806 | 33.59 kg/m2 STANDARD_DEVIATION 6.025 |
| Duration of Diabetes (Years) | 15.2 Years STANDARD_DEVIATION 7.96 | 15.3 Years STANDARD_DEVIATION 7.93 | 15.3 Years STANDARD_DEVIATION 7.92 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 59 Participants | 128 Participants | 69 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 223 Participants | 436 Participants | 213 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 1 Participants |
| HbA1c (%) | 8.49 HbA1c (%) STANDARD_DEVIATION 1.027 | 8.50 HbA1c (%) STANDARD_DEVIATION 1.027 | 8.51 HbA1c (%) STANDARD_DEVIATION 1.029 |
| NAb result Negative | 5 Participants | 6 Participants | 1 Participants |
| NAb result Not Tested | 279 Participants | 561 Participants | 282 Participants |
| NAb result Positive | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 15 Participants | 27 Participants | 12 Participants |
| Race (NIH/OMB) Black or African American | 35 Participants | 71 Participants | 36 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 6 Participants | 5 Participants |
| Race (NIH/OMB) White | 227 Participants | 452 Participants | 225 Participants |
| Region of Enrollment United States | 284 Participants | 567 Participants | 283 Participants |
| Sex: Female, Male Female | 104 Participants | 226 Participants | 122 Participants |
| Sex: Female, Male Male | 180 Participants | 341 Participants | 161 Participants |
| Thyroid Disease Absence | 243 Participants | 472 Participants | 229 Participants |
| Thyroid Disease Hyperthyroidism | 2 Participants | 2 Participants | 0 Participants |
| Thyroid Disease Hypothyroidism | 34 Participants | 79 Participants | 45 Participants |
| Thyroid Disease Other | 4 Participants | 12 Participants | 8 Participants |
| Thyroid Disease Presence | 41 Participants | 95 Participants | 54 Participants |
| Thyroid Disease Structural abnormality | 1 Participants | 2 Participants | 1 Participants |
| Thyroid Disease Thyroid Cancer | 0 Participants | 0 Participants | 0 Participants |
| Weight (kg) | 98.011 Weight (kg) STANDARD_DEVIATION 20.0532 | 98.076 Weight (kg) STANDARD_DEVIATION 20.2732 | 98.141 Weight (kg) STANDARD_DEVIATION 20.5269 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 281 | 0 / 282 |
| other Total, other adverse events | 125 / 281 | 122 / 282 |
| serious Total, serious adverse events | 15 / 281 | 16 / 282 |
Outcome results
Primary
Treatment-induced Anti-Insulin Antibody (TI-AIA) is the Primary Endpoint
Subjects were classified as experiencing a TI-AIA or not. A TI-AIA is defined as a subject experiencing a newly confirmed positive AIA status, if they were negative at baseline or a 4-fold increase in their titer values if they were positive. The primary outcome measure is summarized as the percent of subjects experiencing a TI-AIA in the group.
Time frame: Baseline 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 (NUMBER) |
|---|---|---|
| Gan & Lee Insulin Glargine Injection | Treatment-induced Anti-Insulin Antibody (TI-AIA) is the Primary Endpoint | 54 Percentage of subjects with TI-AIA |
| Lantus® | Treatment-induced Anti-Insulin Antibody (TI-AIA) is the Primary Endpoint | 60 Percentage of subjects with TI-AIA |
Comparison: This is a two-arm study.90% CI: [-7.6, 3.5]
Secondary
CFB in HbA1c to Week 26
Change is HbA1c value at week 26 minus the value at baseline.
Time frame: Baseline 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 | CFB in HbA1c to Week 26 | -0.39 Percentage of glycosylated hemoglobin | Standard Error 0.079 |
| Lantus® | CFB in HbA1c to Week 26 | -0.45 Percentage of glycosylated hemoglobin | Standard Error 0.079 |
Secondary
Efficacy - HbA1c Control
The number and percentage of subjects who achieve a HbA1c of \< 7.0% at visit Week 26.
Time frame: At Week 26
Population: HbA1c control (HbA1c \< 7.0%)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Gan & Lee Insulin Glargine Injection | Efficacy - HbA1c Control | Lack of Postbaseline HbA1c Control | 249 Participants |
| Gan & Lee Insulin Glargine Injection | Efficacy - HbA1c Control | Sufficient Postbaseline HbA1c Control | 35 Participants |
| Lantus® | Efficacy - HbA1c Control | Lack of Postbaseline HbA1c Control | 246 Participants |
| Lantus® | Efficacy - HbA1c Control | Sufficient Postbaseline HbA1c Control | 37 Participants |
Secondary
Efficacy - Postbaseline FBG Control
The number and percentage of subjects who achieve an FBG test result of ≤ 8.0 mmol/L (≤ 144.0 mg/dL) at visit Week 26.
Time frame: Baseline to Week 26
Population: FBG control (FBG ≤ 8.0 mmol/L)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Gan & Lee Insulin Glargine Injection | Efficacy - Postbaseline FBG Control | Lack of Postbaseline FBG control | 151 Participants |
| Gan & Lee Insulin Glargine Injection | Efficacy - Postbaseline FBG Control | Sufficient Postbaseline FBG control | 133 Participants |
| Lantus® | Efficacy - Postbaseline FBG Control | Lack of Postbaseline FBG control | 145 Participants |
| Lantus® | Efficacy - Postbaseline FBG Control | Sufficient Postbaseline FBG control | 138 Participants |
Secondary
Immunogenicity - 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: Baseline to Week 26
Population: Subjects with Confirmed Positive Anti-Insulin Antibodies at Baseline with non-missing post-baseline AIA titer values (n=3).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gan & Lee Insulin Glargine Injection | Immunogenicity - Mean Change From Baseline in Each Treatment Group in AIA Titers After Baseline | 23.5 Titers | Standard Deviation 19.09 |
| Lantus® | Immunogenicity - Mean Change From Baseline in Each Treatment Group in AIA Titers After Baseline | -3.0 Titers | — |
Secondary
Immunogenicity - Percentage of Subjects in Each Treatment Group With Confirmed Positive AIA at Baseline Who Developed at Least a 4-fold Increase in Titers After Baseline
The percentage of subjects in each treatment group with confirmed positive AIA at baseline (n=6) who developed an important increase (at least a 4-fold increase in titers after baseline) up to visit Week 26.
Time frame: Baseline to Week 26
Population: Subset of subjects in each treatment group with confirmed positive AIA at baseline (n=6).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Gan & Lee Insulin Glargine Injection | Immunogenicity - Percentage of Subjects in Each Treatment Group With Confirmed Positive AIA at Baseline Who Developed at Least a 4-fold Increase in Titers After Baseline | 0 Participants |
| Lantus® | Immunogenicity - Percentage of Subjects in Each Treatment Group With Confirmed Positive AIA at Baseline Who Developed at Least a 4-fold Increase in Titers After Baseline | 0 Participants |
Secondary
Immunogenicity - Percentage of Subjects in Each Treatment Group With Negative AIA at Baseline Who Develop Confirmed Positive AIA After Baseline
The percentage 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: Baseline to Week 26
Population: Subset of subjects whose baseline AIA was negative (n=511).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Gan & Lee Insulin Glargine Injection | Immunogenicity - Percentage of Subjects in Each Treatment Group With Negative AIA at Baseline Who Develop Confirmed Positive AIA After Baseline | 42 Participants |
| Lantus® | Immunogenicity - Percentage of Subjects in Each Treatment Group With Negative AIA at Baseline Who Develop Confirmed Positive AIA After Baseline | 53 Participants |
Secondary
Immunogenicity - Percentage of Subjects With Confirmed Positive AIA After Baseline
The percentage of subjects in each treatment group with confirmed positive AIA after baseline and up to visit Week 26.
Time frame: Baseline to Week 26
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Gan & Lee Insulin Glargine Injection | Immunogenicity - Percentage of Subjects With Confirmed Positive AIA After Baseline | 58 Participants |
| Lantus® | Immunogenicity - Percentage of Subjects With Confirmed Positive AIA After Baseline | 61 Participants |
Secondary
Immunogenicity - Percentage of Subjects With Confirmed Positive AIA After Baseline Who Develop Any Anti-insulin Neutralizing Antibodies After Baseline
The percentage 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: Baseline to Week 26
Population: Percentage of subjects in each treatment group with confirmed positive AIA after baseline and up to visit Week 26.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Gan & Lee Insulin Glargine Injection | Immunogenicity - Percentage of Subjects With Confirmed Positive AIA After Baseline Who Develop Any Anti-insulin Neutralizing Antibodies After Baseline | 1 Participants |
| Lantus® | Immunogenicity - Percentage of Subjects With Confirmed Positive AIA After Baseline Who Develop Any Anti-insulin Neutralizing Antibodies After Baseline | 3 Participants |