Trial Outcomes & Findings for Recent-Onset Type 1 Diabetes Trial Evaluating Efficacy and Safety of Teplizumab (NCT NCT03875729)
NCT ID: NCT03875729
Last Updated: 2024-04-24
Results Overview
The area under the concentration-time curve (AUC) of C-peptide was measured after a 4-hour mixed meal tolerance test (MMTT) and is a measure of endogenous insulin production and β cell function. The AUC was computed using the trapezoidal rule and standardized by the duration of the MMTT test, i.e., AUC was divided by the last blood sample collection time (240 minutes or the last collection time for 4h MMTT).
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
328 participants
Primary outcome timeframe
Baseline to Week 78
Results posted on
2024-04-24
Participant Flow
The first participant was enrolled on April 5, 2019, and the last participant was enrolled on November 4, 2021.
Of 422 assessed for eligibility, 328 met inclusion criteria and were randomized to treatment.
Participant milestones
| Measure |
Placebo
Placebo: Control
Placebo was administered via intravenous infusion in two courses, with the first course starting on Day 1 (Week 1) and the second course approximately 6 months later at Day 182 (Week 26). Participants who were unable to receive the second 12-day course due to COronaVIrus Disease of 2019 (COVID-19) pandemic restrictions were given the second course at approximately 12 months (Week 52) in a modified dosing schedule. Each course of treatment included daily infusions for 12 days.
The placebo solution consisted of the same formulation as the study drug but without teplizumab.
Placebo was administered in the same dose volume and by the same treatment schedule as the active drug.
|
Teplizumab
Teplizumab: Treatment
Teplizumab was administered via intravenous infusion in two courses, with the first course starting on Day 1 (Week 1) and the second course approximately 6 months later at Day 182 (Week 26). Participants who were unable to receive the second 12-day course due to COronaVIrus Disease of 2019 (COVID-19) pandemic restrictions were given the second course at approximately 12 months (Week 52) in a modified dosing schedule. Each course of treatment included daily infusions for 12 days.
Each course included:
* Day 1: 106 μg/m\^2
* Day 2: 425 μg/m\^2
* Days 3-12: 850 μg/m\^2 Total per course: 9.0 mg/m\^2 The doses of study drug were calculated based on the participant's body surface area (BSA) measured on the first day of each treatment course.
|
|---|---|---|
|
Overall Study
STARTED
|
111
|
217
|
|
Overall Study
COMPLETED
|
101
|
195
|
|
Overall Study
NOT COMPLETED
|
10
|
22
|
Reasons for withdrawal
| Measure |
Placebo
Placebo: Control
Placebo was administered via intravenous infusion in two courses, with the first course starting on Day 1 (Week 1) and the second course approximately 6 months later at Day 182 (Week 26). Participants who were unable to receive the second 12-day course due to COronaVIrus Disease of 2019 (COVID-19) pandemic restrictions were given the second course at approximately 12 months (Week 52) in a modified dosing schedule. Each course of treatment included daily infusions for 12 days.
The placebo solution consisted of the same formulation as the study drug but without teplizumab.
Placebo was administered in the same dose volume and by the same treatment schedule as the active drug.
|
Teplizumab
Teplizumab: Treatment
Teplizumab was administered via intravenous infusion in two courses, with the first course starting on Day 1 (Week 1) and the second course approximately 6 months later at Day 182 (Week 26). Participants who were unable to receive the second 12-day course due to COronaVIrus Disease of 2019 (COVID-19) pandemic restrictions were given the second course at approximately 12 months (Week 52) in a modified dosing schedule. Each course of treatment included daily infusions for 12 days.
Each course included:
* Day 1: 106 μg/m\^2
* Day 2: 425 μg/m\^2
* Days 3-12: 850 μg/m\^2 Total per course: 9.0 mg/m\^2 The doses of study drug were calculated based on the participant's body surface area (BSA) measured on the first day of each treatment course.
|
|---|---|---|
|
Overall Study
Adverse Event
|
0
|
5
|
|
Overall Study
Withdrawal by Subject
|
8
|
11
|
|
Overall Study
Pregnancy
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
0
|
5
|
|
Overall Study
Personal reasons
|
2
|
0
|
Baseline Characteristics
Populations differs due to missing values.
Baseline characteristics by cohort
| Measure |
Placebo
n=111 Participants
Placebo: Control
|
Teplizumab
n=217 Participants
Teplizumab: Treatment
|
Total
n=328 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
111 Participants
n=111 Participants
|
217 Participants
n=217 Participants
|
328 Participants
n=328 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=111 Participants
|
0 Participants
n=217 Participants
|
0 Participants
n=328 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=111 Participants
|
0 Participants
n=217 Participants
|
0 Participants
n=328 Participants
|
|
Age, Continuous
|
12.3 years
STANDARD_DEVIATION 2.55 • n=111 Participants
|
12.0 years
STANDARD_DEVIATION 2.53 • n=217 Participants
|
12.1 years
STANDARD_DEVIATION 2.54 • n=328 Participants
|
|
Sex: Female, Male
Female
|
42 Participants
n=111 Participants
|
98 Participants
n=217 Participants
|
140 Participants
n=328 Participants
|
|
Sex: Female, Male
Male
|
69 Participants
n=111 Participants
|
119 Participants
n=217 Participants
|
188 Participants
n=328 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
4 Participants
n=111 Participants
|
14 Participants
n=217 Participants
|
18 Participants
n=328 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
101 Participants
n=111 Participants
|
193 Participants
n=217 Participants
|
294 Participants
n=328 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
6 Participants
n=111 Participants
|
10 Participants
n=217 Participants
|
16 Participants
n=328 Participants
|
|
Race/Ethnicity, Customized
White
|
94 Participants
n=111 Participants
|
189 Participants
n=217 Participants
|
283 Participants
n=328 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
6 Participants
n=111 Participants
|
5 Participants
n=217 Participants
|
11 Participants
n=328 Participants
|
|
Race/Ethnicity, Customized
Asian
|
3 Participants
n=111 Participants
|
4 Participants
n=217 Participants
|
7 Participants
n=328 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaskan Native
|
0 Participants
n=111 Participants
|
1 Participants
n=217 Participants
|
1 Participants
n=328 Participants
|
|
Race/Ethnicity, Customized
Native Hawiian or Other Pacific Islander
|
1 Participants
n=111 Participants
|
0 Participants
n=217 Participants
|
1 Participants
n=328 Participants
|
|
Race/Ethnicity, Customized
Multiple
|
0 Participants
n=111 Participants
|
6 Participants
n=217 Participants
|
6 Participants
n=328 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 Participants
n=111 Participants
|
4 Participants
n=217 Participants
|
5 Participants
n=328 Participants
|
|
Race/Ethnicity, Customized
Not reported
|
6 Participants
n=111 Participants
|
8 Participants
n=217 Participants
|
14 Participants
n=328 Participants
|
|
Region of Enrollment
Canada
|
7 participants
n=111 Participants
|
13 participants
n=217 Participants
|
20 participants
n=328 Participants
|
|
Region of Enrollment
Belgium
|
4 participants
n=111 Participants
|
1 participants
n=217 Participants
|
5 participants
n=328 Participants
|
|
Region of Enrollment
United States
|
56 participants
n=111 Participants
|
126 participants
n=217 Participants
|
182 participants
n=328 Participants
|
|
Region of Enrollment
Czechia
|
10 participants
n=111 Participants
|
17 participants
n=217 Participants
|
27 participants
n=328 Participants
|
|
Region of Enrollment
Poland
|
15 participants
n=111 Participants
|
33 participants
n=217 Participants
|
48 participants
n=328 Participants
|
|
Region of Enrollment
United Kingdom
|
6 participants
n=111 Participants
|
6 participants
n=217 Participants
|
12 participants
n=328 Participants
|
|
Region of Enrollment
France
|
5 participants
n=111 Participants
|
9 participants
n=217 Participants
|
14 participants
n=328 Participants
|
|
Region of Enrollment
Germany
|
8 participants
n=111 Participants
|
12 participants
n=217 Participants
|
20 participants
n=328 Participants
|
|
Peak C-peptide at screening
0.2 - 0.7 pmol/mL
|
47 Participants
n=111 Participants
|
91 Participants
n=217 Participants
|
138 Participants
n=328 Participants
|
|
Peak C-peptide at screening
>0.7 pmol/mL
|
64 Participants
n=111 Participants
|
126 Participants
n=217 Participants
|
190 Participants
n=328 Participants
|
|
Age group at randomization
8 - 12 years
|
62 Participants
n=111 Participants
|
120 Participants
n=217 Participants
|
182 Participants
n=328 Participants
|
|
Age group at randomization
>12 - 17 years
|
49 Participants
n=111 Participants
|
97 Participants
n=217 Participants
|
146 Participants
n=328 Participants
|
|
Number of positive type 1 diabetes (T1D) autoantibodies
None
|
0 Participants
n=111 Participants
|
1 Participants
n=217 Participants
|
1 Participants
n=328 Participants
|
|
Number of positive type 1 diabetes (T1D) autoantibodies
One
|
3 Participants
n=111 Participants
|
10 Participants
n=217 Participants
|
13 Participants
n=328 Participants
|
|
Number of positive type 1 diabetes (T1D) autoantibodies
Two
|
13 Participants
n=111 Participants
|
38 Participants
n=217 Participants
|
51 Participants
n=328 Participants
|
|
Number of positive type 1 diabetes (T1D) autoantibodies
Three
|
30 Participants
n=111 Participants
|
47 Participants
n=217 Participants
|
77 Participants
n=328 Participants
|
|
Number of positive type 1 diabetes (T1D) autoantibodies
Four
|
39 Participants
n=111 Participants
|
66 Participants
n=217 Participants
|
105 Participants
n=328 Participants
|
|
Number of positive type 1 diabetes (T1D) autoantibodies
Five
|
26 Participants
n=111 Participants
|
55 Participants
n=217 Participants
|
81 Participants
n=328 Participants
|
|
History of diabetic ketoacidosis (DKA)
Yes
|
4 Participants
n=111 Participants
|
0 Participants
n=217 Participants
|
4 Participants
n=328 Participants
|
|
History of diabetic ketoacidosis (DKA)
No
|
107 Participants
n=111 Participants
|
217 Participants
n=217 Participants
|
324 Participants
n=328 Participants
|
|
Human leukocyte antigen (HLA) genotyping - DR3
Positive
|
56 Participants
n=109 Participants • Populations differs due to missing values.
|
96 Participants
n=215 Participants • Populations differs due to missing values.
|
152 Participants
n=324 Participants • Populations differs due to missing values.
|
|
Human leukocyte antigen (HLA) genotyping - DR3
Negative
|
53 Participants
n=109 Participants • Populations differs due to missing values.
|
119 Participants
n=215 Participants • Populations differs due to missing values.
|
172 Participants
n=324 Participants • Populations differs due to missing values.
|
|
Human leukocyte antigen (HLA) genotyping - DR4
Positive
|
75 Participants
n=109 Participants • Populations differs due to missing values.
|
137 Participants
n=215 Participants • Populations differs due to missing values.
|
212 Participants
n=324 Participants • Populations differs due to missing values.
|
|
Human leukocyte antigen (HLA) genotyping - DR4
Negative
|
34 Participants
n=109 Participants • Populations differs due to missing values.
|
78 Participants
n=215 Participants • Populations differs due to missing values.
|
112 Participants
n=324 Participants • Populations differs due to missing values.
|
|
Anti-glutamic acid decarboxylase 65 (GAD65) autoantibody
Positive
|
96 Participants
n=111 Participants
|
183 Participants
n=217 Participants
|
279 Participants
n=328 Participants
|
|
Anti-glutamic acid decarboxylase 65 (GAD65) autoantibody
Negative
|
15 Participants
n=111 Participants
|
34 Participants
n=217 Participants
|
49 Participants
n=328 Participants
|
|
Anti-islet antigen 2 (IA-2) autoantibody
Positive
|
87 Participants
n=111 Participants
|
165 Participants
n=217 Participants
|
252 Participants
n=328 Participants
|
|
Anti-islet antigen 2 (IA-2) autoantibody
Negative
|
24 Participants
n=111 Participants
|
52 Participants
n=217 Participants
|
76 Participants
n=328 Participants
|
|
Anti-zinc transporter 8 (ZnT8) autoantibody
Positive
|
83 Participants
n=111 Participants
|
162 Participants
n=217 Participants
|
245 Participants
n=328 Participants
|
|
Anti-zinc transporter 8 (ZnT8) autoantibody
Negative
|
28 Participants
n=111 Participants
|
55 Participants
n=217 Participants
|
83 Participants
n=328 Participants
|
|
Anti-insulin autoantibody
Positive
|
85 Participants
n=111 Participants
|
144 Participants
n=217 Participants
|
229 Participants
n=328 Participants
|
|
Anti-insulin autoantibody
Negative
|
26 Participants
n=111 Participants
|
73 Participants
n=217 Participants
|
99 Participants
n=328 Participants
|
|
Anti-islet cell cytoplasmic antibody (ICA)
Positive
|
54 Participants
n=111 Participants
|
112 Participants
n=217 Participants
|
166 Participants
n=328 Participants
|
|
Anti-islet cell cytoplasmic antibody (ICA)
Negative
|
57 Participants
n=111 Participants
|
105 Participants
n=217 Participants
|
162 Participants
n=328 Participants
|
|
Height
|
158.48 cm
STANDARD_DEVIATION 14.977 • n=111 Participants
|
155.35 cm
STANDARD_DEVIATION 15.358 • n=217 Participants
|
156.41 cm
STANDARD_DEVIATION 15.279 • n=328 Participants
|
|
Weight
|
49.19 kg
STANDARD_DEVIATION 15.889 • n=111 Participants
|
46.68 kg
STANDARD_DEVIATION 14.992 • n=217 Participants
|
47.53 kg
STANDARD_DEVIATION 15.323 • n=328 Participants
|
|
Body mass index (BMI)
|
19.063 kg/m^2
STANDARD_DEVIATION 3.6415 • n=111 Participants
|
18.868 kg/m^2
STANDARD_DEVIATION 3.4517 • n=217 Participants
|
18.934 kg/m^2
STANDARD_DEVIATION 3.5127 • n=328 Participants
|
|
Body mass index (BMI) z-score
|
0.0557 z-score
STANDARD_DEVIATION 1.0957 • n=111 Participants
|
0.0627 z-score
STANDARD_DEVIATION 1.0723 • n=217 Participants
|
0.0603 z-score
STANDARD_DEVIATION 1.0786 • n=328 Participants
|
|
C-peptide area under concentration-time curve standardized by mixed meal tolerance test duration
|
0.7237 pmol/mL
STANDARD_DEVIATION 0.3190 • n=111 Participants
|
0.7445 pmol/mL
STANDARD_DEVIATION 0.3653 • n=217 Participants
|
0.7375 pmol/mL
STANDARD_DEVIATION 0.3499 • n=328 Participants
|
|
Insulin use
|
0.383 U/kg/day
STANDARD_DEVIATION 0.2535 • n=63 Participants • Insulin use at baseline was not calculated for participants who did not have at least 3 days of data recorded on the insulin diary before the start of the study.
|
0.447 U/kg/day
STANDARD_DEVIATION 0.3093 • n=126 Participants • Insulin use at baseline was not calculated for participants who did not have at least 3 days of data recorded on the insulin diary before the start of the study.
|
0.426 U/kg/day
STANDARD_DEVIATION 0.2928 • n=189 Participants • Insulin use at baseline was not calculated for participants who did not have at least 3 days of data recorded on the insulin diary before the start of the study.
|
|
Glycated hemoglobin (HbA1c)
|
9.18 Percentage of glycated hemoglobin
STANDARD_DEVIATION 1.918 • n=110 Participants • Population differs due to missing value for one participant.
|
8.90 Percentage of glycated hemoglobin
STANDARD_DEVIATION 1.729 • n=217 Participants • Population differs due to missing value for one participant.
|
9.00 Percentage of glycated hemoglobin
STANDARD_DEVIATION 1.797 • n=327 Participants • Population differs due to missing value for one participant.
|
|
Time from type 1 diabetes (T1D) diagnosis to randomization
|
5.20 weeks
STANDARD_DEVIATION 0.812 • n=111 Participants
|
5.37 weeks
STANDARD_DEVIATION 0.730 • n=217 Participants
|
5.31 weeks
STANDARD_DEVIATION 0.762 • n=328 Participants
|
PRIMARY outcome
Timeframe: Baseline to Week 78Population: Intent-to-treat (ITT) and Per Protocol (PP). The main reason participants were excluded from the PP population was for treatment compliance \<80% (15 of 16 excluded participants in the placebo group and 32 of 37 in the teplizumab group). Other reasons included took prohibited medication (1 in placebo group, 3 in teplizumab group), received incorrect treatment (2 in teplizumab group), and pregnancy (1 in teplizumab group).
The area under the concentration-time curve (AUC) of C-peptide was measured after a 4-hour mixed meal tolerance test (MMTT) and is a measure of endogenous insulin production and β cell function. The AUC was computed using the trapezoidal rule and standardized by the duration of the MMTT test, i.e., AUC was divided by the last blood sample collection time (240 minutes or the last collection time for 4h MMTT).
Outcome measures
| Measure |
Placebo
n=111 Participants
Placebo: Control
|
Teplizumab
n=217 Participants
Teplizumab: Treatment
|
|---|---|---|
|
Change in C-peptide ln(AUC+1) Standardized by Duration of the Mixed Meal Tolerance Test (MMTT)
Intent-to-treat
|
-0.2112 pmol/mL
Interval -0.2437 to -0.1786
|
-0.0859 pmol/mL
Interval -0.109 to -0.0628
|
|
Change in C-peptide ln(AUC+1) Standardized by Duration of the Mixed Meal Tolerance Test (MMTT)
Per Protocol
|
-0.2185 pmol/mL
Interval -0.2501 to -0.1869
|
-0.0800 pmol/mL
Interval -0.103 to -0.057
|
SECONDARY outcome
Timeframe: Week 78Population: Intent-to-treat and Per Protocol
The average daily insulin use was calculated based on participants who have at least 3 days of insulin use recorded in the dairy for the Week 78 visit.
Outcome measures
| Measure |
Placebo
n=111 Participants
Placebo: Control
|
Teplizumab
n=217 Participants
Teplizumab: Treatment
|
|---|---|---|
|
Average Daily Exogenous Insulin Use
Intent-to-treat
|
0.593 Units/kg/day
Interval 0.47 to 0.716
|
0.463 Units/kg/day
Interval 0.363 to 0.562
|
|
Average Daily Exogenous Insulin Use
Per Protocol
|
0.613 Units/kg/day
Interval 0.538 to 0.687
|
0.446 Units/kg/day
Interval 0.39 to 0.502
|
SECONDARY outcome
Timeframe: Baseline to Week 78Population: Intent-to-treat and Per Protocol
Change in percentage (%) glycated hemoglobin (HbA1c)
Outcome measures
| Measure |
Placebo
n=111 Participants
Placebo: Control
|
Teplizumab
n=217 Participants
Teplizumab: Treatment
|
|---|---|---|
|
Change in Glycated Hemoglobin (HbA1c) Levels (%)
Intent-to-treat
|
-1.89 Percentage of glycated hemoglobin
Interval -2.16 to -1.62
|
-1.98 Percentage of glycated hemoglobin
Interval -2.17 to -1.78
|
|
Change in Glycated Hemoglobin (HbA1c) Levels (%)
Per Protocol
|
-1.94 Percentage of glycated hemoglobin
Interval -2.21 to -1.67
|
-2.07 Percentage of glycated hemoglobin
Interval -2.27 to -1.87
|
SECONDARY outcome
Timeframe: Week 78Population: Intent-to-treat and Per Protocol
Time in range (%) for glycemia control was assessed using Continuous Glucose Monitoring (CGM). Time in range was defined as daily average percentage of time a participant's glucose is \>= 70 mg/dL and \<=180 mg/dL. Time in range was calculated based on participants who had at least 3 days of CGM data recorded for Week 78 visit with a range of at least 8 hours on a given day.
Outcome measures
| Measure |
Placebo
n=111 Participants
Placebo: Control
|
Teplizumab
n=217 Participants
Teplizumab: Treatment
|
|---|---|---|
|
Time in Range for Glycemia Control
Intent-to-treat
|
62.65 Percentage of time in range
Interval 57.38 to 67.92
|
67.36 Percentage of time in range
Interval 63.7 to 71.03
|
|
Time in Range for Glycemia Control
Per Protocol
|
61.44 Percentage of time in range
Interval 56.5 to 66.38
|
67.61 Percentage of time in range
Interval 64.09 to 71.14
|
SECONDARY outcome
Timeframe: During the entire study (from the first dose to the last study contact, up to 78 Weeks)Population: Intent-to-treat and Per Protocol
Rate = clinically important hypoglycemic events/patient-year. A clinically important episode was defined as a blood glucose value of \<54 mg/dL (3.0 mmol/L) (i.e., Level 2 Hypoglycemia, International Hypoglycemia Study Group, 2017) or a hypoglycemia event of severe cognitive impairment requiring external assistance (such as seizure, syncope, severe confusion with or without a confirmatory low blood glucose reading) (i.e., Level 3 Hypoglycemia, International Hypoglycemia Study Group 2017). Event rate was calculated for each participant as number of events / total study follow-up time. Total study follow-up time was calculated as (the date of last study contact - the first dose date + 1)/365.25. The summary is based on the data reported post-baseline in the Hypoglycemic Events Electronic Diary (eDiary).
Outcome measures
| Measure |
Placebo
n=111 Participants
Placebo: Control
|
Teplizumab
n=217 Participants
Teplizumab: Treatment
|
|---|---|---|
|
Rate of Clinically Important Hypoglycemic Events
Intent-to-treat
|
4.24 Events/patient-year
Interval 3.06 to 5.89
|
4.68 Events/patient-year
Interval 3.7 to 5.91
|
|
Rate of Clinically Important Hypoglycemic Events
Per protocol
|
4.63 Events/patient-year
Interval 3.31 to 6.49
|
5.04 Events/patient-year
Interval 3.94 to 6.44
|
SECONDARY outcome
Timeframe: During the entire study (from the first dose to the last study contact, up to 78 Weeks)Population: Safety population = all randomized study participants receiving any exposure to study drug.
AESIs are defined in the protocol and categories in the statistical analysis plan. Participants with multiple events are counted only once for each preferred term and category.
Outcome measures
| Measure |
Placebo
n=111 Participants
Placebo: Control
|
Teplizumab
n=217 Participants
Teplizumab: Treatment
|
|---|---|---|
|
Number of Participants With Adverse Events of Special Interest (AESIs)
Treatment-emergent AESI
|
24 Participants
|
63 Participants
|
|
Number of Participants With Adverse Events of Special Interest (AESIs)
Participants with at least one >= grade 3 neutropenia
|
0 Participants
|
7 Participants
|
|
Number of Participants With Adverse Events of Special Interest (AESIs)
Participants with at least one >= grade 3 infection
|
2 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events of Special Interest (AESIs)
Participants with at least one acute mononucleosis-like illness
|
3 Participants
|
17 Participants
|
|
Number of Participants With Adverse Events of Special Interest (AESIs)
Participants with at least one lymphoma or other malignancy, including benign tumors
|
1 Participants
|
2 Participants
|
|
Number of Participants With Adverse Events of Special Interest (AESIs)
Participants with at least one instance of severe hypoglycemic event
|
18 Participants
|
29 Participants
|
|
Number of Participants With Adverse Events of Special Interest (AESIs)
Participants with at least one >=grade 3 liver function abnormality
|
0 Participants
|
8 Participants
|
|
Number of Participants With Adverse Events of Special Interest (AESIs)
Participants with at least one >= grade 3 thrombocytopenia
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events of Special Interest (AESIs)
Participants with at least one >= grade 4 allergic/hypersensitivity reaction
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events of Special Interest (AESIs)
Participants with at least one >= grade 3 rash
|
0 Participants
|
4 Participants
|
SECONDARY outcome
Timeframe: Pre-dose samples collected on Days 1, 4, 9, 12 and 28 for each of the two treatment courses, and one post-dose sample collected on Day 9 during the first treatment course.Population: The Pharmacokinetic (PK) population includes all randomized participants who received at least one dose of teplizumab with at least one valid pharmacokinetic sample.
PK samples were collected prior to dosing except for Day 9 in Course 1. An additional PK sample was collected 45 minutes after infusion on Day 9 in Course 1. Concentration values below Lower Limit of Quantification (2.50 ng/mL) were set to zero for summary statistics. Course 2 day numbers were set relative to the first day of dosing, regardless of normal or modified dosing schedule.
Outcome measures
| Measure |
Placebo
n=217 Participants
Placebo: Control
|
Teplizumab
Teplizumab: Treatment
|
|---|---|---|
|
Teplizumab Serum Concentrations
Course 1, Day 1
|
7.4271 ng/mL
Geometric Coefficient of Variation 628.114
|
—
|
|
Teplizumab Serum Concentrations
Course 1, Day 4
|
70.4769 ng/mL
Geometric Coefficient of Variation 50.767
|
—
|
|
Teplizumab Serum Concentrations
Course 1, Day 9
|
250.3928 ng/mL
Geometric Coefficient of Variation 44.677
|
—
|
|
Teplizumab Serum Concentrations
Course 1, Day 9 post-dose
|
636.4390 ng/mL
Geometric Coefficient of Variation 33.171
|
—
|
|
Teplizumab Serum Concentrations
Course 1, Day 12
|
305.6569 ng/mL
Geometric Coefficient of Variation 47.048
|
—
|
|
Teplizumab Serum Concentrations
Course 1, Day 28
|
25.0317 ng/mL
Geometric Coefficient of Variation 79.953
|
—
|
|
Teplizumab Serum Concentrations
Course 2, Day 1
|
5.5433 ng/mL
Geometric Coefficient of Variation 522.457
|
—
|
|
Teplizumab Serum Concentrations
Course 2, Day 4
|
82.0166 ng/mL
Geometric Coefficient of Variation 50.333
|
—
|
|
Teplizumab Serum Concentrations
Course 2, Day 9
|
145.9498 ng/mL
Geometric Coefficient of Variation 75.737
|
—
|
|
Teplizumab Serum Concentrations
Course 2, Day 12
|
108.2988 ng/mL
Geometric Coefficient of Variation 107.776
|
—
|
|
Teplizumab Serum Concentrations
Course 2, Day 28
|
13.2159 ng/mL
Geometric Coefficient of Variation 181.421
|
—
|
SECONDARY outcome
Timeframe: Baseline through 78 WeekPopulation: The Immunogenicity population includes all randomized participants who received at least one dose of teplizumab with at least one valid serum Anti-teplizumab Antibody (ADA) sample.
Baseline was defined as the most recent value collected prior to the first dose of study drug. Week 26 Day 187 and Weeks 27 and 34 are planned for subjects under the normal dosing schedule. Week 52 Day 369 and Weeks 53, 56, and 60 are planned for subjects under the modified dosing schedule.
Outcome measures
| Measure |
Placebo
n=217 Participants
Placebo: Control
|
Teplizumab
Teplizumab: Treatment
|
|---|---|---|
|
Anti-teplizumab Antibody (ADA) Titers After Treatment Courses
Baseline
|
65.81 Titer
Geometric Coefficient of Variation 182.3
|
—
|
|
Anti-teplizumab Antibody (ADA) Titers After Treatment Courses
Week 2
|
177.22 Titer
Geometric Coefficient of Variation 278.2
|
—
|
|
Anti-teplizumab Antibody (ADA) Titers After Treatment Courses
Week 4
|
817.08 Titer
Geometric Coefficient of Variation 275.0
|
—
|
|
Anti-teplizumab Antibody (ADA) Titers After Treatment Courses
Week 8
|
1040.58 Titer
Geometric Coefficient of Variation 239.1
|
—
|
|
Anti-teplizumab Antibody (ADA) Titers After Treatment Courses
Week 26 Day 182
|
834.86 Titer
Geometric Coefficient of Variation 226.1
|
—
|
|
Anti-teplizumab Antibody (ADA) Titers After Treatment Courses
Week 26 Day 187
|
807.26 Titer
Geometric Coefficient of Variation 681.6
|
—
|
|
Anti-teplizumab Antibody (ADA) Titers After Treatment Courses
Week 27
|
9257.15 Titer
Geometric Coefficient of Variation 222.3
|
—
|
|
Anti-teplizumab Antibody (ADA) Titers After Treatment Courses
Week 30
|
9985.29 Titer
Geometric Coefficient of Variation 218.7
|
—
|
|
Anti-teplizumab Antibody (ADA) Titers After Treatment Courses
Week 34
|
7326.91 Titer
Geometric Coefficient of Variation 237.0
|
—
|
|
Anti-teplizumab Antibody (ADA) Titers After Treatment Courses
Week 39
|
3701.64 Titer
Geometric Coefficient of Variation 202.8
|
—
|
|
Anti-teplizumab Antibody (ADA) Titers After Treatment Courses
Week 52 Day 364
|
1398.22 Titer
Geometric Coefficient of Variation 240.1
|
—
|
|
Anti-teplizumab Antibody (ADA) Titers After Treatment Courses
Week 52 Day 369
|
308.80 Titer
Geometric Coefficient of Variation 207.5
|
—
|
|
Anti-teplizumab Antibody (ADA) Titers After Treatment Courses
Week 53
|
8043.22 Titer
Geometric Coefficient of Variation 165.7
|
—
|
|
Anti-teplizumab Antibody (ADA) Titers After Treatment Courses
Week 56
|
14221.44 Titer
Geometric Coefficient of Variation 241.8
|
—
|
|
Anti-teplizumab Antibody (ADA) Titers After Treatment Courses
Week 60
|
9040.49 Titer
Geometric Coefficient of Variation 299.4
|
—
|
|
Anti-teplizumab Antibody (ADA) Titers After Treatment Courses
Week 65
|
996.15 Titer
Geometric Coefficient of Variation 484.4
|
—
|
|
Anti-teplizumab Antibody (ADA) Titers After Treatment Courses
Week 78
|
672.13 Titer
Geometric Coefficient of Variation 332.4
|
—
|
SECONDARY outcome
Timeframe: From baseline through Week 78Population: The Immunogenicity population includes all randomized participants who received at least one dose of teplizumab with at least one valid serum Anti-teplizumab Antibody (ADA) sample.
Baseline is defined as the most recent value collected prior to the first dose of study drug. Week 26 Day 187 and Weeks 27 and 34 are planned for subjects under the normal dosing schedule. Week 52 Day 369 and Weeks 53, 56, and 60 are planned for subjects under the modified dosing schedule.
Outcome measures
| Measure |
Placebo
n=217 Participants
Placebo: Control
|
Teplizumab
Teplizumab: Treatment
|
|---|---|---|
|
Incidence of Anti-drug Antibodies (ADA) After Treatment Courses
Week 2 · Positive
|
182 Participants
|
—
|
|
Incidence of Anti-drug Antibodies (ADA) After Treatment Courses
Week 2 · Negative
|
25 Participants
|
—
|
|
Incidence of Anti-drug Antibodies (ADA) After Treatment Courses
Week 4 · Positive
|
178 Participants
|
—
|
|
Incidence of Anti-drug Antibodies (ADA) After Treatment Courses
Week 4 · Negative
|
26 Participants
|
—
|
|
Incidence of Anti-drug Antibodies (ADA) After Treatment Courses
Week 52 Day 364 · Positive
|
155 Participants
|
—
|
|
Incidence of Anti-drug Antibodies (ADA) After Treatment Courses
Week 60 · Positive
|
17 Participants
|
—
|
|
Incidence of Anti-drug Antibodies (ADA) After Treatment Courses
Week 60 · Negative
|
1 Participants
|
—
|
|
Incidence of Anti-drug Antibodies (ADA) After Treatment Courses
Baseline · Positive
|
15 Participants
|
—
|
|
Incidence of Anti-drug Antibodies (ADA) After Treatment Courses
Baseline · Negative
|
200 Participants
|
—
|
|
Incidence of Anti-drug Antibodies (ADA) After Treatment Courses
Week 8 · Positive
|
175 Participants
|
—
|
|
Incidence of Anti-drug Antibodies (ADA) After Treatment Courses
Week 8 · Negative
|
31 Participants
|
—
|
|
Incidence of Anti-drug Antibodies (ADA) After Treatment Courses
Week 26 Day 182 · Positive
|
139 Participants
|
—
|
|
Incidence of Anti-drug Antibodies (ADA) After Treatment Courses
Week 26 Day 182 · Negative
|
53 Participants
|
—
|
|
Incidence of Anti-drug Antibodies (ADA) After Treatment Courses
Week 26 Day 187 · Positive
|
130 Participants
|
—
|
|
Incidence of Anti-drug Antibodies (ADA) After Treatment Courses
Week 26 Day 187 · Negative
|
40 Participants
|
—
|
|
Incidence of Anti-drug Antibodies (ADA) After Treatment Courses
Week 27 · Positive
|
167 Participants
|
—
|
|
Incidence of Anti-drug Antibodies (ADA) After Treatment Courses
Week 27 · Negative
|
8 Participants
|
—
|
|
Incidence of Anti-drug Antibodies (ADA) After Treatment Courses
Week 30 · Positive
|
169 Participants
|
—
|
|
Incidence of Anti-drug Antibodies (ADA) After Treatment Courses
Week 30 · Negative
|
7 Participants
|
—
|
|
Incidence of Anti-drug Antibodies (ADA) After Treatment Courses
Week 34 · Positive
|
163 Participants
|
—
|
|
Incidence of Anti-drug Antibodies (ADA) After Treatment Courses
Week 34 · Negative
|
13 Participants
|
—
|
|
Incidence of Anti-drug Antibodies (ADA) After Treatment Courses
Week 39 · Positive
|
170 Participants
|
—
|
|
Incidence of Anti-drug Antibodies (ADA) After Treatment Courses
Week 39 · Negative
|
22 Participants
|
—
|
|
Incidence of Anti-drug Antibodies (ADA) After Treatment Courses
Week 52 Day 364 · Negative
|
37 Participants
|
—
|
|
Incidence of Anti-drug Antibodies (ADA) After Treatment Courses
Week 52 Day 369 · Positive
|
11 Participants
|
—
|
|
Incidence of Anti-drug Antibodies (ADA) After Treatment Courses
Week 52 Day 369 · Negative
|
4 Participants
|
—
|
|
Incidence of Anti-drug Antibodies (ADA) After Treatment Courses
Week 53 · Positive
|
15 Participants
|
—
|
|
Incidence of Anti-drug Antibodies (ADA) After Treatment Courses
Week 53 · Negative
|
1 Participants
|
—
|
|
Incidence of Anti-drug Antibodies (ADA) After Treatment Courses
Week 56 · Positive
|
18 Participants
|
—
|
|
Incidence of Anti-drug Antibodies (ADA) After Treatment Courses
Week 56 · Negative
|
1 Participants
|
—
|
|
Incidence of Anti-drug Antibodies (ADA) After Treatment Courses
Week 65 · Positive
|
153 Participants
|
—
|
|
Incidence of Anti-drug Antibodies (ADA) After Treatment Courses
Week 65 · Negative
|
38 Participants
|
—
|
|
Incidence of Anti-drug Antibodies (ADA) After Treatment Courses
Week 78 · Positive
|
146 Participants
|
—
|
|
Incidence of Anti-drug Antibodies (ADA) After Treatment Courses
Week 78 · Negative
|
45 Participants
|
—
|
Adverse Events
Placebo
Serious events: 6 serious events
Other events: 88 other events
Deaths: 0 deaths
Teplizumab
Serious events: 12 serious events
Other events: 212 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=111 participants at risk
Safety population
|
Teplizumab
n=217 participants at risk
Safety population
|
|---|---|---|
|
Injury, poisoning and procedural complications
Concussion
|
0.00%
0/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
0.46%
1/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Cardiac disorders
Palpitation
|
0.00%
0/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
0.46%
1/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Nervous system disorders
Syncope
|
0.90%
1/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
0.00%
0/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Immune system disorders
Cytokine release syndrome
|
0.00%
0/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
1.4%
3/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
0.46%
1/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Gastrointestinal disorders
Constipation
|
0.90%
1/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
0.00%
0/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Skin and subcutaneous tissue disorders
Dermatitis atopic
|
0.00%
0/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
0.46%
1/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Psychiatric disorders
Suicidal ideation
|
0.00%
0/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
0.92%
2/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Psychiatric disorders
Suicide attempt
|
0.00%
0/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
0.46%
1/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Psychiatric disorders
Anxiety
|
0.90%
1/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
0.00%
0/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.00%
0/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
0.46%
1/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Infections and infestations
Device related bacteraemia
|
0.90%
1/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
0.00%
0/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Infections and infestations
Gastroenteritis
|
1.8%
2/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
0.00%
0/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.90%
1/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
0.46%
1/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
0.46%
1/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
Other adverse events
| Measure |
Placebo
n=111 participants at risk
Safety population
|
Teplizumab
n=217 participants at risk
Safety population
|
|---|---|---|
|
Vascular disorders
Hypotension
|
9.0%
10/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
8.3%
18/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
General disorders
Pyrexia
|
9.9%
11/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
24.4%
53/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
General disorders
Fatigue
|
13.5%
15/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
10.1%
22/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
General disorders
Chills
|
0.00%
0/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
8.8%
19/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Immune system disorders
Cytokine release syndrome
|
0.90%
1/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
7.4%
16/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
10.8%
12/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
9.2%
20/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
5.4%
6/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
8.8%
19/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
14.4%
16/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
8.8%
19/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
3.6%
4/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
5.1%
11/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Investigations
Lymphocyte count decreased
|
4.5%
5/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
33.6%
73/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Investigations
White blood cell count decreased
|
5.4%
6/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
24.4%
53/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Investigations
Neutrophil count decreased
|
9.9%
11/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
15.2%
33/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
12.9%
28/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Investigations
Aspartate Aminotransferase increased
|
0.90%
1/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
9.2%
20/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Cardiac disorders
Tachycardia
|
0.90%
1/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
5.5%
12/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Nervous system disorders
Headache
|
18.9%
21/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
43.3%
94/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Nervous system disorders
Dizziness
|
4.5%
5/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
5.1%
11/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Blood and lymphatic system disorders
Lymphopenia
|
0.00%
0/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
23.0%
50/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.90%
1/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
12.9%
28/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.90%
1/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
12.0%
26/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Blood and lymphatic system disorders
Anaemia
|
4.5%
5/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
6.0%
13/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Gastrointestinal disorders
Nausea
|
18.9%
21/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
42.4%
92/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Gastrointestinal disorders
Vomiting
|
13.5%
15/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
31.3%
68/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Gastrointestinal disorders
Abdominal pain
|
8.1%
9/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
17.1%
37/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Gastrointestinal disorders
Abdominal pain upper
|
10.8%
12/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
14.3%
31/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Gastrointestinal disorders
Diarrhoea
|
10.8%
12/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
14.3%
31/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Skin and subcutaneous tissue disorders
Rash
|
4.5%
5/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
39.6%
86/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
3.6%
4/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
13.4%
29/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
8.1%
9/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
7.8%
17/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Skin and subcutaneous tissue disorders
Rash macular
|
0.00%
0/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
5.1%
11/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
5.4%
6/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
4.1%
9/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Skin and subcutaneous tissue disorders
Erythema
|
5.4%
6/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
3.2%
7/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Renal and urinary disorders
Proteinuria
|
2.7%
3/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
6.5%
14/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
5.4%
6/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
6.9%
15/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Infections and infestations
COVID-19
|
23.4%
26/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
22.6%
49/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Infections and infestations
Upper respiratory tract infection
|
20.7%
23/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
20.3%
44/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Infections and infestations
Nasopharyngitis
|
12.6%
14/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
8.8%
19/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Infections and infestations
Gastroenteritis
|
9.0%
10/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
4.1%
9/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
73.0%
81/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
69.6%
151/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Metabolism and nutrition disorders
Decreased appetite
|
2.7%
3/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
5.1%
11/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
4.5%
5/111 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
6.5%
14/217 • Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Sponsor has right to publish multi-center study results first, then PI may publish/present study results after Sponsor had at least 60 days and up to 105 days to review/comment/obtain intellectual property protection, PI has deleted all sponsor-requested references to confidential information, and PI has considered the Sponsor's proposed revisions in good faith and meets with the Sponsor to discuss/ resolve any disagreements regarding accuracy, data analyses or confidential information.
- Publication restrictions are in place
Restriction type: OTHER