Diabetes Mellitus, Type 2
Conditions
Brief summary
The study compares two semaglutide medicines and looks at how well they control blood sugar levels, in participants with type 2 diabetes (T2D). Participants will either get the currently available semaglutide or the semaglutide which is produced through a new manufacturing process. Participants need to take one injection of semaglutide once a week, on the same day of every week. Participants will have a total of 11 clinic visits and the study will last for about 35 weeks (approximately 8 months).
Interventions
DRUGSemaglutide J
Participants will initially receive 0.25 mg subcutaneous injections of semaglutide J OW and the dose will be then escalated once in 4 weeks for 8 weeks until the target maintenance dose of 1.0 mg is reached which will be maintained for a period of 20 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 28).
DRUGSemaglutide B
Participants will initially receive 0.25 mg subcutaneous injections of semaglutide B OW and the dose will be then escalated once in 4 weeks for 8 weeks until the target maintenance dose of 1.0 mg is reached which will be maintained for a period of 20 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 28).
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosed with type 2 diabetes (T2D) mellitus greater than equal to (≥) 180 days before screening. * Stable daily dose(s) ≥ 90 days prior to the day of screening of metformin ≥ 1500 milligrams (mg) or maximum tolerated or effective dose. * HbA1c of 7.0-10.5 percentage (%) \[53-91.3 millimoles per mole (mmol/mol)\] (both inclusive).
Exclusion criteria
* Known or suspected hypersensitivity to study intervention(s) or related products. * Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within 90 days before screening. However, short term insulin treatment for a maximum of 14 days and prior insulin treatment for gestational diabetes are allowed. * Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within 90 days before screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for nondilated examination.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Glycosylated Haemoglobin (HbA1c) | From baseline (week 0) to end of treatment (week 28) | Change in HbA1c from baseline (week 0) to end of treatment (week 28) is presented. The endpoint was evaluated based on the data from in-study period. The in-study period is defined as the uninterrupted time interval from date of randomisation to date of least contact with trial site. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Treatment-Emergent Adverse Events (TEAEs) | From the time of first dosing (week 0) to end of study (week 33) | An AE is any untoward medical occurrence in a clinical study participant that is temporally associated with the use of IMP, whether or not considered related to the IMP. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom or disease (new or exacerbated) temporally associated with the use of an IMP. All presented adverse events are TEAE. A TEAE is defined as an adverse event with an onset date (or increase in severity) during the on-treatment observation period. On-treatment observation period is defined as from first drug date until the end of study. |
| Occurrence of Anti-semaglutide Antibodies (Yes/no) | From baseline (week 0) to end of study (week 33) | Occurrence of anti-semaglutide antibodies for in-study observation period is presented. The in-study period is defined as the uninterrupted time interval from date of randomisation to date of last contact with trial site. In the reported data 'yes' infers who tested positive for anti-semaglutide antibodies, whereas 'No' infers who tested negative for anti semaglutide antibodies. |
| Occurrence of Anti-semaglutide Antibodies With In-vitro Neutralising Effect (Yes/no) | From baseline (week 0) to end of study (week 33) | Occurrence of anti-semaglutide antibodies with in-vitro neutralizing effect was to be performed based on positive cross -reactivity to GLP-1. Since there was no sample with positive cross -reactivity to GLP-1, no further analysis was performed for invitro neutralizing effect towards native-GLP1. Therefore, no data is available for this end point. In the reported data 'yes' infers who tested positive for anti-semaglutide antibodies whereas 'No' infers who tested negative for anti-semaglutide antibodies. |
| Change in Body Weight | From baseline (week 0) to end of treatment (week 28) | Change in body weight from baseline (week 0) to end of treatment (week 28) is presented. The endpoint was evaluated based on the data from in-study period. The in-study period is defined as the uninterrupted time interval from date of randomisation to date of least contact with trial site. |
| Occurrence of In-vitro Neutralising Cross-reacting Antibodies to Endogenous GLP-1 (Yes/no) | At week 33 | Occurrence of in-vitro neutralising cross-reacting antibodies to endogenous GLP-1 at week 33 is presented. In the reported data 'yes' infers who tested positive for in-vitro neutralising cross-reacting antibodies to endogenous GLP-1 whereas 'No' infers who tested negative for in-vitro neutralising cross-reacting antibodies to endogenous GLP-1. |
| Anti-semaglutide Antibodies Level Measured as Percentage (%) Bound/Total | At week 33 | Anti-semaglutide antibodies level measured as %Bound/Total at week 33 is presented. |
| Anti-semaglutide Antibodies Level (Measured as Titre) | At week 33 | Anti-semaglutide antibodies level measured as titre at week 33 is presented. |
| Occurrence of Anti-semaglutide Binding Antibodies Cross-reacting With Endogenous Glucagon Like Peptide-1 (GLP-1) (Yes/no) | From baseline (week 0) to end of study (week 33) | Occurrence of anti-semaglutide binding antibodies cross-reacting with endogenous glucagon like peptide-1 (GLP-1) for in-study observation period is presented. The in-study period is defined as the uninterrupted time interval from date of randomisation to date of last contact with trial site. In the reported data 'yes' infers who tested positive for anti-semaglutide binding antibodies cross-reacting with endogenous glucagon like peptide-1 (GLP-1) whereas 'No' infers who tested negative for anti-semaglutide binding antibodies cross-reacting with endogenous glucagon like peptide-1 (GLP-1). |
Countries
Canada, Poland, Slovakia, South Africa, United States
Participant flow
Recruitment details
The trial was conducted at 73 sites in Slovakia, Poland, South Africa, the United States and Canada.
Participants by arm
| Arm | Count |
|---|---|
| Semaglutide J Participants initially received 0.25 mg subcutaneous injections of semaglutide J once weekly and the dose was then escalated (0.25 mg in week 0 to week 4 and 0.5 mg in week 4 to week 8) once in 4 weeks until the target maintenance dose of 1.0 mg was reached which was maintained for a period of 20 weeks. Total treatment period was 28 weeks. | 291 |
| Semaglutide B Participants initially received 0.25 mg subcutaneous injections of semaglutide B once weekly and the dose was then escalated (0.25 mg in week 0 to week 4 and 0.5 mg in week 4 to week 8) once in 4 weeks until the target maintenance dose of 1.0 mg was reached which was maintained for a period of 20 weeks. Total treatment period was 28 weeks. | 97 |
| Total | 388 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
| Overall Study | Lost to Follow-up | 4 | 2 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 3 |
Baseline characteristics
| Characteristic | Semaglutide B | Total | Semaglutide J |
|---|---|---|---|
| Age, Continuous | 54.8 Years STANDARD_DEVIATION 7.1 | 54.0 Years STANDARD_DEVIATION 7.6 | 53.7 Years STANDARD_DEVIATION 7.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 25 Participants | 81 Participants | 56 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 72 Participants | 307 Participants | 235 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 12 Participants | 39 Participants | 27 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 60 Participants | 48 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 72 Participants | 286 Participants | 214 Participants |
| Sex: Female, Male Female | 47 Participants | 175 Participants | 128 Participants |
| Sex: Female, Male Male | 50 Participants | 213 Participants | 163 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 291 | 0 / 97 |
| other Total, other adverse events | 64 / 291 | 24 / 97 |
| serious Total, serious adverse events | 8 / 291 | 5 / 97 |
Outcome results
Primary
Change in Glycosylated Haemoglobin (HbA1c)
Change in HbA1c from baseline (week 0) to end of treatment (week 28) is presented. The endpoint was evaluated based on the data from in-study period. The in-study period is defined as the uninterrupted time interval from date of randomisation to date of least contact with trial site.
Time frame: From baseline (week 0) to end of treatment (week 28)
Population: Full analysis set included all randomised participants. Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide J | Change in Glycosylated Haemoglobin (HbA1c) | -1.7 Percentage of glycosylated haemoglobin | Standard Deviation 1 |
| Semaglutide B | Change in Glycosylated Haemoglobin (HbA1c) | -1.6 Percentage of glycosylated haemoglobin | Standard Deviation 1 |
p-value: <0.000195% CI: [-0.3, 0.08]ANCOVA
Secondary
Anti-semaglutide Antibodies Level Measured as Percentage (%) Bound/Total
Anti-semaglutide antibodies level measured as %Bound/Total at week 33 is presented.
Time frame: At week 33
Population: Safety analysis set included all participants who are exposed to study intervention. Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide J | Anti-semaglutide Antibodies Level Measured as Percentage (%) Bound/Total | 3.47 Percentage of Antisemaglutide Antibodies | Standard Deviation 0 |
Secondary
Anti-semaglutide Antibodies Level (Measured as Titre)
Anti-semaglutide antibodies level measured as titre at week 33 is presented.
Time frame: At week 33
Population: Safety analysis set included all participants who are exposed to study intervention. Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide J | Anti-semaglutide Antibodies Level (Measured as Titre) | 15.00 Titre | Standard Deviation 0 |
Secondary
Change in Body Weight
Change in body weight from baseline (week 0) to end of treatment (week 28) is presented. The endpoint was evaluated based on the data from in-study period. The in-study period is defined as the uninterrupted time interval from date of randomisation to date of least contact with trial site.
Time frame: From baseline (week 0) to end of treatment (week 28)
Population: Full analysis set included all randomised participants. Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide J | Change in Body Weight | -5.0 Kilogram (kg) | Standard Deviation 5 |
| Semaglutide B | Change in Body Weight | -4.6 Kilogram (kg) | Standard Deviation 4.4 |
Secondary
Number of Treatment-Emergent Adverse Events (TEAEs)
An AE is any untoward medical occurrence in a clinical study participant that is temporally associated with the use of IMP, whether or not considered related to the IMP. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom or disease (new or exacerbated) temporally associated with the use of an IMP. All presented adverse events are TEAE. A TEAE is defined as an adverse event with an onset date (or increase in severity) during the on-treatment observation period. On-treatment observation period is defined as from first drug date until the end of study.
Time frame: From the time of first dosing (week 0) to end of study (week 33)
Population: Safety analysis set included all participants who are exposed to study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Semaglutide J | Number of Treatment-Emergent Adverse Events (TEAEs) | 156 Events |
| Semaglutide B | Number of Treatment-Emergent Adverse Events (TEAEs) | 52 Events |
Secondary
Occurrence of Anti-semaglutide Antibodies With In-vitro Neutralising Effect (Yes/no)
Occurrence of anti-semaglutide antibodies with in-vitro neutralizing effect was to be performed based on positive cross -reactivity to GLP-1. Since there was no sample with positive cross -reactivity to GLP-1, no further analysis was performed for invitro neutralizing effect towards native-GLP1. Therefore, no data is available for this end point. In the reported data 'yes' infers who tested positive for anti-semaglutide antibodies whereas 'No' infers who tested negative for anti-semaglutide antibodies.
Time frame: From baseline (week 0) to end of study (week 33)
Population: Since there was no sample with positive cross -reactivity to GLP-1, no further analysis was performed for invitro neutralizing effect towards native-GLP1. Therefore, no data is available for this end point.
Secondary
Occurrence of Anti-semaglutide Antibodies (Yes/no)
Occurrence of anti-semaglutide antibodies for in-study observation period is presented. The in-study period is defined as the uninterrupted time interval from date of randomisation to date of last contact with trial site. In the reported data 'yes' infers who tested positive for anti-semaglutide antibodies, whereas 'No' infers who tested negative for anti semaglutide antibodies.
Time frame: From baseline (week 0) to end of study (week 33)
Population: Safety analysis set included all participants who are exposed to study intervention. Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Semaglutide J | Occurrence of Anti-semaglutide Antibodies (Yes/no) | Yes | 1 Participants |
| Semaglutide J | Occurrence of Anti-semaglutide Antibodies (Yes/no) | No | 281 Participants |
| Semaglutide B | Occurrence of Anti-semaglutide Antibodies (Yes/no) | Yes | 0 Participants |
| Semaglutide B | Occurrence of Anti-semaglutide Antibodies (Yes/no) | No | 90 Participants |
Secondary
Occurrence of Anti-semaglutide Binding Antibodies Cross-reacting With Endogenous Glucagon Like Peptide-1 (GLP-1) (Yes/no)
Occurrence of anti-semaglutide binding antibodies cross-reacting with endogenous glucagon like peptide-1 (GLP-1) for in-study observation period is presented. The in-study period is defined as the uninterrupted time interval from date of randomisation to date of last contact with trial site. In the reported data 'yes' infers who tested positive for anti-semaglutide binding antibodies cross-reacting with endogenous glucagon like peptide-1 (GLP-1) whereas 'No' infers who tested negative for anti-semaglutide binding antibodies cross-reacting with endogenous glucagon like peptide-1 (GLP-1).
Time frame: From baseline (week 0) to end of study (week 33)
Population: Safety analysis set included all participants who are exposed to study intervention. Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Semaglutide J | Occurrence of Anti-semaglutide Binding Antibodies Cross-reacting With Endogenous Glucagon Like Peptide-1 (GLP-1) (Yes/no) | Yes | 0 Participants |
| Semaglutide J | Occurrence of Anti-semaglutide Binding Antibodies Cross-reacting With Endogenous Glucagon Like Peptide-1 (GLP-1) (Yes/no) | No | 1 Participants |
| Semaglutide B | Occurrence of Anti-semaglutide Binding Antibodies Cross-reacting With Endogenous Glucagon Like Peptide-1 (GLP-1) (Yes/no) | Yes | 0 Participants |
| Semaglutide B | Occurrence of Anti-semaglutide Binding Antibodies Cross-reacting With Endogenous Glucagon Like Peptide-1 (GLP-1) (Yes/no) | No | 0 Participants |
Secondary
Occurrence of In-vitro Neutralising Cross-reacting Antibodies to Endogenous GLP-1 (Yes/no)
Occurrence of in-vitro neutralising cross-reacting antibodies to endogenous GLP-1 at week 33 is presented. In the reported data 'yes' infers who tested positive for in-vitro neutralising cross-reacting antibodies to endogenous GLP-1 whereas 'No' infers who tested negative for in-vitro neutralising cross-reacting antibodies to endogenous GLP-1.
Time frame: At week 33
Population: Safety analysis set included all participants who are exposed to study intervention. Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Semaglutide J | Occurrence of In-vitro Neutralising Cross-reacting Antibodies to Endogenous GLP-1 (Yes/no) | Yes | 0 Participants |
| Semaglutide J | Occurrence of In-vitro Neutralising Cross-reacting Antibodies to Endogenous GLP-1 (Yes/no) | No | 1 Participants |
| Semaglutide B | Occurrence of In-vitro Neutralising Cross-reacting Antibodies to Endogenous GLP-1 (Yes/no) | Yes | 0 Participants |
| Semaglutide B | Occurrence of In-vitro Neutralising Cross-reacting Antibodies to Endogenous GLP-1 (Yes/no) | No | 0 Participants |