Type1 Diabetes Mellitus
Conditions
Brief summary
This is a randomized, placebo-controlled, double-blind study to evaluate the efficacy, safety, and pharmacodynamics (PD) of multiple doses of REMD-477 in subjects who have Type 1 diabetes and are currently receiving insulin treatment. This study will determine whether REMD-477 can decrease daily insulin requirements and improve glycemic control after 12 weeks of treatment in subjects diagnosed with Type 1 diabetes with fasting C-peptide \< 0.7 ng/mL at Screening. The study will be conducted at multiple sites in the United States. Approximately 150 subjects with type 1 diabetes on stable doses of insulin will be randomized in a 1:1:1 fashion into one of three treatment groups.
Interventions
BIOLOGICALREMD-477
Administered as repeated SC doses in subjects with Type 1 Diabetes
BIOLOGICALPlacebo Comparator
Administered as a repeated SC doses in subjects with Type 1 Diabetes
Sponsors
REMD Biotherapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Men and women between the ages of 18 and 65 years old, inclusive, at the time of screening; * Females of non-child bearing potential must be ≥1 year post-menopausal (confirmed by a serum follicle-stimulating hormone (FSH) levels ≥ 40 IU/mL) or documented as being surgically sterile. Females of child bearing potential must agree to use two methods of contraception; * Male subjects must be willing to use clinically acceptable method of contraception during the entire study; * Body mass index between 18.5 and 32 kg/m2, inclusive, at screening; * Diagnosed with Type 1 diabetes, based on clinical history or as defined by the current American Diabetes Association (ADA) criteria; * HbA1c \> 7% and \< 10 % at screening; * Fasting C-peptide \< 0.7 ng/mL; * Treatment with a stable insulin regimen for at least 8 weeks before screening with multiple daily insulin (MDI) injections or continue subcutaneous insulin infusion (CSII) * Willing to use continuous CGM system (e.g. DexCom) throughout the study; * Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤ 1.5x upper limit of normal (ULN) at screening; * Able to provide written informed consent approved by an Institutional Review Board (IRB).
Exclusion criteria
* History or evidence of clinically-significant disorder or condition that, in the opinion of the Investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion; * Significant organ system dysfunction (e.g., clinically significant pulmonary or cardiovascular disease, anemia \[Hemoglobin \< 10.0 g/dL\], known hemoglobinopathies, and renal dysfunction \[eGFR \< 60 ml/min\]); * Any severe symptomatic hypoglycemic event associated with a seizure or requiring help from other people or medical facility in the past 6 months; * Myocardial infarction, unstable angina, revascularization procedure, or cerebrovascular accident ≤12 weeks before screening; * History of New York Heart Association Functional Classification III-IV cardiac disease; * Current or recent (within 1 month of screening) use of diabetes medications other than insulin - subjects on an SGLT2 inhibitor should be discontinue the SGLT2 inhibitor during the Screening Period, at least 2 weeks prior to the start of the Lead-in Period; * Use of steroids and/or other prescribed or over-the-counter medications that are known to affect the outcome measures in this study or known to influence glucose metabolism; * Smokes \> 10 cigarettes/day, and/or is unwilling to abstain from smoking during admission periods; * Known sensitivity to mammalian-derived drug preparations, recombinant protein-based drugs or to humanized or human antibodies; * History of illicit drug use or alcohol abuse within the last 6 months or a positive drug urine test result at screening; * History of pancreatitis, pancreatic neuroendocrine tumors or multiple endocrine neoplasia (MEN) or family history of MEN; * History of pheochromocytoma, or family history of familial pheochromocytoma; * Known or suspected susceptibility to infectious disease (e.g. taking immunosuppressive agents or has a documented inherited or acquired immunodeficiency); * Known history of positive for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HbsAg), or hepatitis C antibodies (HepC Ab); * Participation in an investigational drug or device trial within 30 days of screening or within 5 times the half-life of the investigational agent in the other clinical study, if known, whichever period is longer; * Blood donor or blood loss \> 500 mL within 30 days of Day 1; * Women who are pregnant or lactating/breastfeeding; * Unable or unwilling to follow the study protocol or who are non-compliant with screening appointments or study visits; * Any other condition(s) that might reduce the chance of obtaining study data, or that might cause safety concerns, or that might compromise the ability to give truly informed consent Other inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Average Daily Total Insulin Use | Baseline and 12 weeks | Change from Baseline in average daily total insulin use at Week 12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline Difference in AUC Glucose Concentrations Following Mixed Meal Tolerance Test (MMTT) - Part A Only | Baseline and 13 weeks; AUC glucose timepoints: 10 minutes prior and just before (time ) initiating the mixed-meal ingestion and at 30, 60 and 120 minutes after the mixed meal ingestion. | Difference from baseline at Week 13 in AUC glucose concentration following the Mixed Meal Tolerance Test (MMTT) after repeated doses of REMD-477. |
| Seven-Point Glucose Profile - Change in Average 24-h Glucose Concentrations | Baseline and 12 weeks | Change from baseline at Week 12 in the average daily 24-h blood glucose concentration as assessed by seven-point glucose profile after repeated doses of REMD-477. The 7-point blood glucose profiles includes measuring glucose via finger stick, at the following times of the day: before each meal, 2 hours after each meal, and at bedtime. The 7-point glucose profiles were obtained for 3 consecutive days before (Day 1) and for 3 consecutive days during week 12. |
| Summary of the Product of Average Daily 24-h Glucose Ratio and Daily Insulin Use Ratio (Day 78 [Week 12]/Baseline) | Baseline and week 12 | The product of the ratio of average glucose (Week 12/Baseline) and ratio of average insulin use (Week 12/Baseline). |
| Change in Hemoglobin A1c From Baseline at Week 13 | Baseline and 13 weeks | Change in Hemoglobin A1c from baseline at Week 13, after repeated doses of REMD-477. |
| Percentage of Subjects With HbA1c Reduction of ≥ 0.4% at Week 13 | Baseline and 13 weeks | Proportion (percentage) of subjects who achieve HbA1c reduction of ≥ 0.4%, after repeated doses of REMD-477 |
| Change in C-peptide Adjusted AUC Following Mixed Meal Tolerance Test (MMTT) | Baseline and 13 weeks; AUC C-peptide timepoints: 10 minutes prior and just before (time 0) initiating the mixed-meal ingestion and at 30, 60 and 120 minutes after the mixed meal ingestion. | Change from baseline at Week 13 in the C-peptide adjusted AUC following MMTT after repeated doses of REMD-477. |
| Change in Baseline Difference in Glucagon Adjusted AUC Following Mixed Meal Tolerance Test (MMTT) - Part A Only | Baseline and 13 weeks; AUC glucagon timepoints: 10 minutes prior and just before (time ) initiating the mixed-meal ingestion and at 30, 60 and 120 minutes after the mixed meal ingestion. | Change from baseline at Week 13 in glucagon adjusted AUC after MMTT challenge, after repeated doses of REMD-477. |
| Continuous Glucose Monitoring (CGM) - Change in Average Daily 24-hour Glucose Concentration at Week 12 | Baseline and 12 weeks | Change from baseline at Week 12 in average daily 24-h blood glucose as assessed by CGM after repeated doses of REMD-477. |
| Summary of REMD-477 Plasma Concentrations | Baseline (Day 1 pre-dose) and Weeks 2, 5, 9, 13 and 16. | REMD-477 serum-concentration after repeated doses of REMD-477. |
| Change in Hemoglobin A1c at Week 13 in Subjects With Baseline HbA1c ≥7.5% | Baseline and 13 weeks | Change in Hemoglobin A1c from baseline at Week 13, after repeated doses of REMD-477. |
| Proportion of Subjects With Targeted Hemoglobin A1C (HbA1c) of ≤ 7.0% at Week 13 | Baseline and 13 weeks | Proportion (percentage) of subjects who achieve target HbA1c reduction of ≤ 7.0% at Week 13, after repeated doses of REMD-477 |
| Continuous Glucose Monitoring (CGM) - Change in Percent Time Spent in Target Blood Glucose Range (70-180 mg/dL) at Week 12 | Baseline and 12 weeks | Change from baseline at Week 12 in percent time spent in target blood glucose range (70-180 mg/dL) after repeated doses of REMD-477. |
| Continuous Glucose Monitoring (CGM) - Change in Percent Time Spent in Hyperglycemia (Blood Glucose Range >180 mg/dL) at Week 12 | Baseline and 12 weeks | Change from baseline at Week 12 in percent time spent in Hyperglycemia (Blood Glucose Range \>180 mg/dL) after repeated doses of REMD-477. |
| Continuous Glucose Monitoring (CGM) - Change in Percent Time Spent in Hypoglycemia (Blood Glucose Range <70 mg/dL) at Week 12 | Baseline and 12 weeks | Change from baseline at Week 12 in percent time spent in Hypoglycemia (Blood Glucose Range \<70 mg/dL) after repeated doses of REMD-477. |
| Continuous Glucose Monitoring (CGM) - Change in Percent Time Spent in Hypoglycemia (Blood Glucose Range <55 mg/dL) at Week 12 | Baseline and 12 weeks | Change from baseline at Week 12 in percent time spent in Hypoglycemia (Blood Glucose Range \<55 mg/dL) after repeated doses of REMD-477. |
| Proportion of Subjects With Positive Anti-REMD-477 Antibodies | Day 1 (pre-dose), Day 85 (Week 13) and Day 162 (Week 24) | Proportion of subjects positive for anti-REMD-477 antibody formation. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part A - 35 mg REMD-477 Administered as a repeated subcutaneous (SC) doses in subjects with Type 1 Diabetes
35 mg REMD-477: Administered as repeated SC doses in subjects with Type 1 Diabetes | 25 |
| Part A - 70 mg REMD-477 Administered as a repeated SC doses in subjects with Type 1 Diabetes
70 mg REMD-477: Administered as repeated SC doses in subjects with Type 1 Diabetes | 25 |
| Part A - Matching Placebo Administered as a repeated SC doses in subjects with Type 1 Diabetes
Placebo Comparator: Administered as a repeated SC doses in subjects with Type 1 Diabetes | 25 |
| Part B - 35 mg REMD-477 Administered as a repeated subcutaneous (SC) doses in subjects with Type 1 Diabetes
35 mg REMD-477: Administered as repeated SC doses in subjects with Type 1 Diabetes | 26 |
| Part B - 70 mg REMD-477 Administered as a repeated subcutaneous (SC) doses in subjects with Type 1 Diabetes
70 mg REMD-477: Administered as repeated SC doses in subjects with Type 1 Diabetes | 26 |
| Part B - Matching Placebo Administered as a repeated subcutaneous (SC) doses in subjects with Type 1 Diabetes
Placebo Comparator: Administered as a repeated SC doses in subjects with Type 1 Diabetes | 27 |
| Total | 154 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 | 4 | 0 |
| Overall Study | Physician Decision | 0 | 1 | 1 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Subject noncompliance | 0 | 0 | 1 | 0 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 2 | 3 | 3 | 0 |
Baseline characteristics
| Characteristic | Part A - 70 mg REMD-477 | Total | Part B - Matching Placebo | Part B - 70 mg REMD-477 | Part A - 35 mg REMD-477 | Part B - 35 mg REMD-477 | Part A - Matching Placebo |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 43 years STANDARD_DEVIATION 13.7 | 42 years STANDARD_DEVIATION 14.08 | 42 years STANDARD_DEVIATION 14.8 | 38 years STANDARD_DEVIATION 14.1 | 41 years STANDARD_DEVIATION 13.1 | 42 years STANDARD_DEVIATION 13.8 | 45 years STANDARD_DEVIATION 14.8 |
| Baseline Average Daily Total Insulin Use Values | 44.21 Units/day STANDARD_DEVIATION 3.194 | 46.23 Units/day STANDARD_DEVIATION 3.247 | 50.03 Units/day STANDARD_DEVIATION 3.238 | 47.06 Units/day STANDARD_DEVIATION 3.365 | 45.99 Units/day STANDARD_DEVIATION 3.194 | 42.60 Units/day STANDARD_DEVIATION 3.299 | 47.51 Units/day STANDARD_DEVIATION 3.194 |
| Baseline Average HbA1c Values | 7.42 Percentage STANDARD_DEVIATION 0.159 | 7.71 Percentage STANDARD_DEVIATION 0.19 | 7.74 Percentage STANDARD_DEVIATION 0.15 | 7.94 Percentage STANDARD_DEVIATION 0.358 | 7.54 Percentage STANDARD_DEVIATION 0.159 | 8.05 Percentage STANDARD_DEVIATION 0.153 | 7.58 Percentage STANDARD_DEVIATION 0.159 |
| Body Mass Index | 27.2 kg/m^2 STANDARD_DEVIATION 4.01 | 26.5 kg/m^2 STANDARD_DEVIATION 3.42 | 25.9 kg/m^2 STANDARD_DEVIATION 3.34 | 26.8 kg/m^2 STANDARD_DEVIATION 3.39 | 25.8 kg/m^2 STANDARD_DEVIATION 2.88 | 25.9 kg/m^2 STANDARD_DEVIATION 3.38 | 27.2 kg/m^2 STANDARD_DEVIATION 3.55 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 18 Participants | 5 Participants | 6 Participants | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants | 136 Participants | 22 Participants | 20 Participants | 25 Participants | 25 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 9 Participants | 0 Participants | 2 Participants | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 4 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 23 Participants | 138 Participants | 27 Participants | 23 Participants | 22 Participants | 21 Participants | 22 Participants |
| Sex: Female, Male Female | 14 Participants | 92 Participants | 12 Participants | 17 Participants | 19 Participants | 15 Participants | 15 Participants |
| Sex: Female, Male Male | 11 Participants | 62 Participants | 15 Participants | 9 Participants | 6 Participants | 11 Participants | 10 Participants |
| Time Since Type 1 Diabetes Diagnosis | 25.1 years STANDARD_DEVIATION 12.7 | 24.25 years STANDARD_DEVIATION 12.3 | 25.4 years STANDARD_DEVIATION 14.4 | 19.6 years STANDARD_DEVIATION 11.7 | 23.7 years STANDARD_DEVIATION 10 | 21.7 years STANDARD_DEVIATION 11.8 | 30 years STANDARD_DEVIATION 13.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 25 | 0 / 25 | 0 / 26 | 0 / 26 | 0 / 27 |
| other Total, other adverse events | 20 / 25 | 18 / 25 | 20 / 25 | 14 / 26 | 18 / 26 | 9 / 27 |
| serious Total, serious adverse events | 0 / 25 | 0 / 25 | 2 / 25 | 1 / 26 | 1 / 26 | 2 / 27 |
Outcome results
Primary
Change in Average Daily Total Insulin Use
Change from Baseline in average daily total insulin use at Week 12
Time frame: Baseline and 12 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A - 35 mg REMD-477 | Change in Average Daily Total Insulin Use | -6.72 Units/day | Standard Error 1.649 |
| Part A - 70 mg REMD-477 | Change in Average Daily Total Insulin Use | -5.25 Units/day | Standard Error 1.634 |
| Part A - Matching Placebo | Change in Average Daily Total Insulin Use | -1.37 Units/day | Standard Error 1.881 |
| Part B - 35 mg REMD-477 | Change in Average Daily Total Insulin Use | -7.59 Units/day | Standard Error 2.142 |
| Part B - 70 mg REMD-477 | Change in Average Daily Total Insulin Use | -6.64 Units/day | Standard Error 2.22 |
| Part B - Matching Placebo | Change in Average Daily Total Insulin Use | -1.27 Units/day | Standard Error 2.103 |
Secondary
Change From Baseline Difference in AUC Glucose Concentrations Following Mixed Meal Tolerance Test (MMTT) - Part A Only
Difference from baseline at Week 13 in AUC glucose concentration following the Mixed Meal Tolerance Test (MMTT) after repeated doses of REMD-477.
Time frame: Baseline and 13 weeks; AUC glucose timepoints: 10 minutes prior and just before (time ) initiating the mixed-meal ingestion and at 30, 60 and 120 minutes after the mixed meal ingestion.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A - 35 mg REMD-477 | Change From Baseline Difference in AUC Glucose Concentrations Following Mixed Meal Tolerance Test (MMTT) - Part A Only | -150.68 min*mg/dL | Standard Error 40.472 |
| Part A - 70 mg REMD-477 | Change From Baseline Difference in AUC Glucose Concentrations Following Mixed Meal Tolerance Test (MMTT) - Part A Only | -115.05 min*mg/dL | Standard Error 40.441 |
| Part A - Matching Placebo | Change From Baseline Difference in AUC Glucose Concentrations Following Mixed Meal Tolerance Test (MMTT) - Part A Only | -66.00 min*mg/dL | Standard Error 43.02 |
Secondary
Change in Baseline Difference in Glucagon Adjusted AUC Following Mixed Meal Tolerance Test (MMTT) - Part A Only
Change from baseline at Week 13 in glucagon adjusted AUC after MMTT challenge, after repeated doses of REMD-477.
Time frame: Baseline and 13 weeks; AUC glucagon timepoints: 10 minutes prior and just before (time ) initiating the mixed-meal ingestion and at 30, 60 and 120 minutes after the mixed meal ingestion.
Population: MMTT was completed in Part A subjects only. Part B subjects did not complete the MMTT.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A - 35 mg REMD-477 | Change in Baseline Difference in Glucagon Adjusted AUC Following Mixed Meal Tolerance Test (MMTT) - Part A Only | 2398.76 min*pmol/L | Standard Error 1172.219 |
| Part A - 70 mg REMD-477 | Change in Baseline Difference in Glucagon Adjusted AUC Following Mixed Meal Tolerance Test (MMTT) - Part A Only | 345.14 min*pmol/L | Standard Error 1001.903 |
| Part A - Matching Placebo | Change in Baseline Difference in Glucagon Adjusted AUC Following Mixed Meal Tolerance Test (MMTT) - Part A Only | 13.40 min*pmol/L | Standard Error 1135.048 |
Secondary
Change in C-peptide Adjusted AUC Following Mixed Meal Tolerance Test (MMTT)
Change from baseline at Week 13 in the C-peptide adjusted AUC following MMTT after repeated doses of REMD-477.
Time frame: Baseline and 13 weeks; AUC C-peptide timepoints: 10 minutes prior and just before (time 0) initiating the mixed-meal ingestion and at 30, 60 and 120 minutes after the mixed meal ingestion.
Population: MMTT was completed in Part A subjects only. MMTT was removed from Part B as part of a protocol amendment, and Part B subjects did not complete the MMTT.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A - 35 mg REMD-477 | Change in C-peptide Adjusted AUC Following Mixed Meal Tolerance Test (MMTT) | 27.33 min*pmol/L | Standard Error 107.029 |
| Part A - 70 mg REMD-477 | Change in C-peptide Adjusted AUC Following Mixed Meal Tolerance Test (MMTT) | 289.93 min*pmol/L | Standard Error 87.212 |
| Part A - Matching Placebo | Change in C-peptide Adjusted AUC Following Mixed Meal Tolerance Test (MMTT) | 166.99 min*pmol/L | Standard Error 96.052 |
Secondary
Change in Hemoglobin A1c at Week 13 in Subjects With Baseline HbA1c ≥7.5%
Change in Hemoglobin A1c from baseline at Week 13, after repeated doses of REMD-477.
Time frame: Baseline and 13 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A - 35 mg REMD-477 | Change in Hemoglobin A1c at Week 13 in Subjects With Baseline HbA1c ≥7.5% | -1.02 Percentage | Standard Error 0.139 |
| Part A - 70 mg REMD-477 | Change in Hemoglobin A1c at Week 13 in Subjects With Baseline HbA1c ≥7.5% | -0.94 Percentage | Standard Error 0.167 |
| Part A - Matching Placebo | Change in Hemoglobin A1c at Week 13 in Subjects With Baseline HbA1c ≥7.5% | -0.70 Percentage | Standard Error 0.141 |
| Part B - 35 mg REMD-477 | Change in Hemoglobin A1c at Week 13 in Subjects With Baseline HbA1c ≥7.5% | -0.93 Percentage | Standard Error 0.173 |
| Part B - 70 mg REMD-477 | Change in Hemoglobin A1c at Week 13 in Subjects With Baseline HbA1c ≥7.5% | -0.54 Percentage | Standard Error 0.168 |
| Part B - Matching Placebo | Change in Hemoglobin A1c at Week 13 in Subjects With Baseline HbA1c ≥7.5% | -0.12 Percentage | Standard Error 0.182 |
Secondary
Change in Hemoglobin A1c From Baseline at Week 13
Change in Hemoglobin A1c from baseline at Week 13, after repeated doses of REMD-477.
Time frame: Baseline and 13 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A - 35 mg REMD-477 | Change in Hemoglobin A1c From Baseline at Week 13 | -0.67 Percentage | Standard Error 0.104 |
| Part A - 70 mg REMD-477 | Change in Hemoglobin A1c From Baseline at Week 13 | -0.66 Percentage | Standard Error 0.105 |
| Part A - Matching Placebo | Change in Hemoglobin A1c From Baseline at Week 13 | -0.43 Percentage | Standard Error 0.109 |
| Part B - 35 mg REMD-477 | Change in Hemoglobin A1c From Baseline at Week 13 | -0.64 Percentage | Standard Error 0.13 |
| Part B - 70 mg REMD-477 | Change in Hemoglobin A1c From Baseline at Week 13 | -0.60 Percentage | Standard Error 0.134 |
| Part B - Matching Placebo | Change in Hemoglobin A1c From Baseline at Week 13 | -0.11 Percentage | Standard Error 0.125 |
Secondary
Continuous Glucose Monitoring (CGM) - Change in Average Daily 24-hour Glucose Concentration at Week 12
Change from baseline at Week 12 in average daily 24-h blood glucose as assessed by CGM after repeated doses of REMD-477.
Time frame: Baseline and 12 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A - 35 mg REMD-477 | Continuous Glucose Monitoring (CGM) - Change in Average Daily 24-hour Glucose Concentration at Week 12 | 0.46 mg/dL/day | Standard Error 2.561 |
| Part A - 70 mg REMD-477 | Continuous Glucose Monitoring (CGM) - Change in Average Daily 24-hour Glucose Concentration at Week 12 | -5.71 mg/dL/day | Standard Error 2.575 |
| Part A - Matching Placebo | Continuous Glucose Monitoring (CGM) - Change in Average Daily 24-hour Glucose Concentration at Week 12 | 0.57 mg/dL/day | Standard Error 2.736 |
| Part B - 35 mg REMD-477 | Continuous Glucose Monitoring (CGM) - Change in Average Daily 24-hour Glucose Concentration at Week 12 | 2.57 mg/dL/day | Standard Error 5.159 |
| Part B - 70 mg REMD-477 | Continuous Glucose Monitoring (CGM) - Change in Average Daily 24-hour Glucose Concentration at Week 12 | -6.05 mg/dL/day | Standard Error 5.435 |
| Part B - Matching Placebo | Continuous Glucose Monitoring (CGM) - Change in Average Daily 24-hour Glucose Concentration at Week 12 | 6.08 mg/dL/day | Standard Error 4.502 |
Secondary
Continuous Glucose Monitoring (CGM) - Change in Percent Time Spent in Hyperglycemia (Blood Glucose Range >180 mg/dL) at Week 12
Change from baseline at Week 12 in percent time spent in Hyperglycemia (Blood Glucose Range \>180 mg/dL) after repeated doses of REMD-477.
Time frame: Baseline and 12 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A - 35 mg REMD-477 | Continuous Glucose Monitoring (CGM) - Change in Percent Time Spent in Hyperglycemia (Blood Glucose Range >180 mg/dL) at Week 12 | 0.21 Percentage of time spent in range | Standard Error 2.766 |
| Part A - 70 mg REMD-477 | Continuous Glucose Monitoring (CGM) - Change in Percent Time Spent in Hyperglycemia (Blood Glucose Range >180 mg/dL) at Week 12 | -7.99 Percentage of time spent in range | Standard Error 2.84 |
| Part A - Matching Placebo | Continuous Glucose Monitoring (CGM) - Change in Percent Time Spent in Hyperglycemia (Blood Glucose Range >180 mg/dL) at Week 12 | -1.11 Percentage of time spent in range | Standard Error 3.015 |
| Part B - 35 mg REMD-477 | Continuous Glucose Monitoring (CGM) - Change in Percent Time Spent in Hyperglycemia (Blood Glucose Range >180 mg/dL) at Week 12 | 1.74 Percentage of time spent in range | Standard Error 3.788 |
| Part B - 70 mg REMD-477 | Continuous Glucose Monitoring (CGM) - Change in Percent Time Spent in Hyperglycemia (Blood Glucose Range >180 mg/dL) at Week 12 | -5.02 Percentage of time spent in range | Standard Error 4.242 |
| Part B - Matching Placebo | Continuous Glucose Monitoring (CGM) - Change in Percent Time Spent in Hyperglycemia (Blood Glucose Range >180 mg/dL) at Week 12 | -0.65 Percentage of time spent in range | Standard Error 3.731 |
Secondary
Continuous Glucose Monitoring (CGM) - Change in Percent Time Spent in Hypoglycemia (Blood Glucose Range <55 mg/dL) at Week 12
Change from baseline at Week 12 in percent time spent in Hypoglycemia (Blood Glucose Range \<55 mg/dL) after repeated doses of REMD-477.
Time frame: Baseline and 12 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A - 35 mg REMD-477 | Continuous Glucose Monitoring (CGM) - Change in Percent Time Spent in Hypoglycemia (Blood Glucose Range <55 mg/dL) at Week 12 | -0.15 Percentage of time spent in range | Standard Error 0.452 |
| Part A - 70 mg REMD-477 | Continuous Glucose Monitoring (CGM) - Change in Percent Time Spent in Hypoglycemia (Blood Glucose Range <55 mg/dL) at Week 12 | 0.27 Percentage of time spent in range | Standard Error 0.457 |
| Part A - Matching Placebo | Continuous Glucose Monitoring (CGM) - Change in Percent Time Spent in Hypoglycemia (Blood Glucose Range <55 mg/dL) at Week 12 | -0.03 Percentage of time spent in range | Standard Error 0.483 |
| Part B - 35 mg REMD-477 | Continuous Glucose Monitoring (CGM) - Change in Percent Time Spent in Hypoglycemia (Blood Glucose Range <55 mg/dL) at Week 12 | -1.31 Percentage of time spent in range | Standard Error 0.45 |
| Part B - 70 mg REMD-477 | Continuous Glucose Monitoring (CGM) - Change in Percent Time Spent in Hypoglycemia (Blood Glucose Range <55 mg/dL) at Week 12 | .25 Percentage of time spent in range | Standard Error 0.512 |
| Part B - Matching Placebo | Continuous Glucose Monitoring (CGM) - Change in Percent Time Spent in Hypoglycemia (Blood Glucose Range <55 mg/dL) at Week 12 | -0.67 Percentage of time spent in range | Standard Error 0.448 |
Secondary
Continuous Glucose Monitoring (CGM) - Change in Percent Time Spent in Hypoglycemia (Blood Glucose Range <70 mg/dL) at Week 12
Change from baseline at Week 12 in percent time spent in Hypoglycemia (Blood Glucose Range \<70 mg/dL) after repeated doses of REMD-477.
Time frame: Baseline and 12 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A - 35 mg REMD-477 | Continuous Glucose Monitoring (CGM) - Change in Percent Time Spent in Hypoglycemia (Blood Glucose Range <70 mg/dL) at Week 12 | -0.82 Percentage of time spent in range | Standard Error 0.773 |
| Part A - 70 mg REMD-477 | Continuous Glucose Monitoring (CGM) - Change in Percent Time Spent in Hypoglycemia (Blood Glucose Range <70 mg/dL) at Week 12 | 0.05 Percentage of time spent in range | Standard Error 0.792 |
| Part A - Matching Placebo | Continuous Glucose Monitoring (CGM) - Change in Percent Time Spent in Hypoglycemia (Blood Glucose Range <70 mg/dL) at Week 12 | -0.03 Percentage of time spent in range | Standard Error 0.483 |
| Part B - 35 mg REMD-477 | Continuous Glucose Monitoring (CGM) - Change in Percent Time Spent in Hypoglycemia (Blood Glucose Range <70 mg/dL) at Week 12 | -2.85 Percentage of time spent in range | Standard Error 1.022 |
| Part B - 70 mg REMD-477 | Continuous Glucose Monitoring (CGM) - Change in Percent Time Spent in Hypoglycemia (Blood Glucose Range <70 mg/dL) at Week 12 | 0.85 Percentage of time spent in range | Standard Error 1.15 |
| Part B - Matching Placebo | Continuous Glucose Monitoring (CGM) - Change in Percent Time Spent in Hypoglycemia (Blood Glucose Range <70 mg/dL) at Week 12 | -0.59 Percentage of time spent in range | Standard Error 1.01 |
Secondary
Continuous Glucose Monitoring (CGM) - Change in Percent Time Spent in Target Blood Glucose Range (70-180 mg/dL) at Week 12
Change from baseline at Week 12 in percent time spent in target blood glucose range (70-180 mg/dL) after repeated doses of REMD-477.
Time frame: Baseline and 12 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A - 35 mg REMD-477 | Continuous Glucose Monitoring (CGM) - Change in Percent Time Spent in Target Blood Glucose Range (70-180 mg/dL) at Week 12 | 0.55 Percentage of time spent in range | Standard Error 2.675 |
| Part A - 70 mg REMD-477 | Continuous Glucose Monitoring (CGM) - Change in Percent Time Spent in Target Blood Glucose Range (70-180 mg/dL) at Week 12 | 7.38 Percentage of time spent in range | Standard Error 2.73 |
| Part A - Matching Placebo | Continuous Glucose Monitoring (CGM) - Change in Percent Time Spent in Target Blood Glucose Range (70-180 mg/dL) at Week 12 | 1.54 Percentage of time spent in range | Standard Error 2.903 |
| Part B - 35 mg REMD-477 | Continuous Glucose Monitoring (CGM) - Change in Percent Time Spent in Target Blood Glucose Range (70-180 mg/dL) at Week 12 | 1.13 Percentage of time spent in range | Standard Error 3.463 |
| Part B - 70 mg REMD-477 | Continuous Glucose Monitoring (CGM) - Change in Percent Time Spent in Target Blood Glucose Range (70-180 mg/dL) at Week 12 | 4.20 Percentage of time spent in range | Standard Error 3.888 |
| Part B - Matching Placebo | Continuous Glucose Monitoring (CGM) - Change in Percent Time Spent in Target Blood Glucose Range (70-180 mg/dL) at Week 12 | 1.19 Percentage of time spent in range | Standard Error 3.409 |
Secondary
Percentage of Subjects With HbA1c Reduction of ≥ 0.4% at Week 13
Proportion (percentage) of subjects who achieve HbA1c reduction of ≥ 0.4%, after repeated doses of REMD-477
Time frame: Baseline and 13 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A - 35 mg REMD-477 | Percentage of Subjects With HbA1c Reduction of ≥ 0.4% at Week 13 | 16 Participants |
| Part A - 70 mg REMD-477 | Percentage of Subjects With HbA1c Reduction of ≥ 0.4% at Week 13 | 17 Participants |
| Part A - Matching Placebo | Percentage of Subjects With HbA1c Reduction of ≥ 0.4% at Week 13 | 9 Participants |
| Part B - 35 mg REMD-477 | Percentage of Subjects With HbA1c Reduction of ≥ 0.4% at Week 13 | 13 Participants |
| Part B - 70 mg REMD-477 | Percentage of Subjects With HbA1c Reduction of ≥ 0.4% at Week 13 | 12 Participants |
| Part B - Matching Placebo | Percentage of Subjects With HbA1c Reduction of ≥ 0.4% at Week 13 | 8 Participants |
Secondary
Proportion of Subjects With Positive Anti-REMD-477 Antibodies
Proportion of subjects positive for anti-REMD-477 antibody formation.
Time frame: Day 1 (pre-dose), Day 85 (Week 13) and Day 162 (Week 24)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A - 35 mg REMD-477 | Proportion of Subjects With Positive Anti-REMD-477 Antibodies | Day 85 (Week 13) | 1 participants |
| Part A - 35 mg REMD-477 | Proportion of Subjects With Positive Anti-REMD-477 Antibodies | Day 1 (Pre-dose) | 2 participants |
| Part A - 35 mg REMD-477 | Proportion of Subjects With Positive Anti-REMD-477 Antibodies | Day 162 (Week 24) | 2 participants |
| Part A - 70 mg REMD-477 | Proportion of Subjects With Positive Anti-REMD-477 Antibodies | Day 85 (Week 13) | 1 participants |
| Part A - 70 mg REMD-477 | Proportion of Subjects With Positive Anti-REMD-477 Antibodies | Day 1 (Pre-dose) | 4 participants |
| Part A - 70 mg REMD-477 | Proportion of Subjects With Positive Anti-REMD-477 Antibodies | Day 162 (Week 24) | 5 participants |
| Part A - Matching Placebo | Proportion of Subjects With Positive Anti-REMD-477 Antibodies | Day 1 (Pre-dose) | 5 participants |
| Part A - Matching Placebo | Proportion of Subjects With Positive Anti-REMD-477 Antibodies | Day 162 (Week 24) | 4 participants |
| Part A - Matching Placebo | Proportion of Subjects With Positive Anti-REMD-477 Antibodies | Day 85 (Week 13) | 4 participants |
Secondary
Proportion of Subjects With Targeted Hemoglobin A1C (HbA1c) of ≤ 7.0% at Week 13
Proportion (percentage) of subjects who achieve target HbA1c reduction of ≤ 7.0% at Week 13, after repeated doses of REMD-477
Time frame: Baseline and 13 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A - 35 mg REMD-477 | Proportion of Subjects With Targeted Hemoglobin A1C (HbA1c) of ≤ 7.0% at Week 13 | 16 Participants |
| Part A - 70 mg REMD-477 | Proportion of Subjects With Targeted Hemoglobin A1C (HbA1c) of ≤ 7.0% at Week 13 | 19 Participants |
| Part A - Matching Placebo | Proportion of Subjects With Targeted Hemoglobin A1C (HbA1c) of ≤ 7.0% at Week 13 | 9 Participants |
| Part B - 35 mg REMD-477 | Proportion of Subjects With Targeted Hemoglobin A1C (HbA1c) of ≤ 7.0% at Week 13 | 12 Participants |
| Part B - 70 mg REMD-477 | Proportion of Subjects With Targeted Hemoglobin A1C (HbA1c) of ≤ 7.0% at Week 13 | 8 Participants |
| Part B - Matching Placebo | Proportion of Subjects With Targeted Hemoglobin A1C (HbA1c) of ≤ 7.0% at Week 13 | 4 Participants |
Secondary
Seven-Point Glucose Profile - Change in Average 24-h Glucose Concentrations
Change from baseline at Week 12 in the average daily 24-h blood glucose concentration as assessed by seven-point glucose profile after repeated doses of REMD-477. The 7-point blood glucose profiles includes measuring glucose via finger stick, at the following times of the day: before each meal, 2 hours after each meal, and at bedtime. The 7-point glucose profiles were obtained for 3 consecutive days before (Day 1) and for 3 consecutive days during week 12.
Time frame: Baseline and 12 weeks
Population: Part A patients' compliance with the recordings of glucose values on paper diary were low, and greater than 50% of the data was missing.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A - 35 mg REMD-477 | Seven-Point Glucose Profile - Change in Average 24-h Glucose Concentrations | 11.02 mg/dL/day | Standard Error 6.697 |
| Part A - 70 mg REMD-477 | Seven-Point Glucose Profile - Change in Average 24-h Glucose Concentrations | -9.43 mg/dL/day | Standard Error 6.83 |
| Part A - Matching Placebo | Seven-Point Glucose Profile - Change in Average 24-h Glucose Concentrations | -4.09 mg/dL/day | Standard Error 9.336 |
| Part B - 35 mg REMD-477 | Seven-Point Glucose Profile - Change in Average 24-h Glucose Concentrations | -4.52 mg/dL/day | Standard Error 9.027 |
| Part B - 70 mg REMD-477 | Seven-Point Glucose Profile - Change in Average 24-h Glucose Concentrations | -3.71 mg/dL/day | Standard Error 9.458 |
| Part B - Matching Placebo | Seven-Point Glucose Profile - Change in Average 24-h Glucose Concentrations | 5.07 mg/dL/day | Standard Error 9.091 |
Secondary
Summary of REMD-477 Plasma Concentrations
REMD-477 serum-concentration after repeated doses of REMD-477.
Time frame: Baseline (Day 1 pre-dose) and Weeks 2, 5, 9, 13 and 16.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A - 35 mg REMD-477 | Summary of REMD-477 Plasma Concentrations | Baseline (Day 1 Pre-dose) | 0 ng/mL | Geometric Coefficient of Variation 0 |
| Part A - 35 mg REMD-477 | Summary of REMD-477 Plasma Concentrations | Week 2 | 1070 ng/mL | Geometric Coefficient of Variation 51 |
| Part A - 35 mg REMD-477 | Summary of REMD-477 Plasma Concentrations | Week 5 | 4650 ng/mL | Geometric Coefficient of Variation 33.9 |
| Part A - 35 mg REMD-477 | Summary of REMD-477 Plasma Concentrations | Week 9 | 6290 ng/mL | Geometric Coefficient of Variation 41.8 |
| Part A - 35 mg REMD-477 | Summary of REMD-477 Plasma Concentrations | Week 13 | 6390 ng/mL | Geometric Coefficient of Variation 45.9 |
| Part A - 35 mg REMD-477 | Summary of REMD-477 Plasma Concentrations | Week 16 | 1430 ng/mL | Geometric Coefficient of Variation 110.4 |
| Part A - 70 mg REMD-477 | Summary of REMD-477 Plasma Concentrations | Week 16 | 7020 ng/mL | Geometric Coefficient of Variation 55.4 |
| Part A - 70 mg REMD-477 | Summary of REMD-477 Plasma Concentrations | Week 9 | 18200 ng/mL | Geometric Coefficient of Variation 34 |
| Part A - 70 mg REMD-477 | Summary of REMD-477 Plasma Concentrations | Baseline (Day 1 Pre-dose) | 0 ng/mL | Geometric Coefficient of Variation 0 |
| Part A - 70 mg REMD-477 | Summary of REMD-477 Plasma Concentrations | Week 5 | 12600 ng/mL | Geometric Coefficient of Variation 68.7 |
| Part A - 70 mg REMD-477 | Summary of REMD-477 Plasma Concentrations | Week 2 | 3600 ng/mL | Geometric Coefficient of Variation 47.9 |
| Part A - 70 mg REMD-477 | Summary of REMD-477 Plasma Concentrations | Week 13 | 19300 ng/mL | Geometric Coefficient of Variation 33 |
| Part A - Matching Placebo | Summary of REMD-477 Plasma Concentrations | Week 2 | 1390 ng/mL | Geometric Coefficient of Variation 47.3 |
| Part A - Matching Placebo | Summary of REMD-477 Plasma Concentrations | Week 5 | 4460 ng/mL | Geometric Coefficient of Variation 54.7 |
| Part A - Matching Placebo | Summary of REMD-477 Plasma Concentrations | Week 9 | 6550 ng/mL | Geometric Coefficient of Variation 37.5 |
| Part A - Matching Placebo | Summary of REMD-477 Plasma Concentrations | Week 16 | 1370 ng/mL | Geometric Coefficient of Variation 84 |
| Part A - Matching Placebo | Summary of REMD-477 Plasma Concentrations | Week 13 | 7040 ng/mL | Geometric Coefficient of Variation 40.6 |
| Part A - Matching Placebo | Summary of REMD-477 Plasma Concentrations | Baseline (Day 1 Pre-dose) | 0 ng/mL | Geometric Coefficient of Variation 0 |
| Part B - 35 mg REMD-477 | Summary of REMD-477 Plasma Concentrations | Week 13 | 15700 ng/mL | Geometric Coefficient of Variation 27.8 |
| Part B - 35 mg REMD-477 | Summary of REMD-477 Plasma Concentrations | Week 16 | 5070 ng/mL | Geometric Coefficient of Variation 51.1 |
| Part B - 35 mg REMD-477 | Summary of REMD-477 Plasma Concentrations | Week 2 | 2780 ng/mL | Geometric Coefficient of Variation 65 |
| Part B - 35 mg REMD-477 | Summary of REMD-477 Plasma Concentrations | Week 9 | 14600 ng/mL | Geometric Coefficient of Variation 26.7 |
| Part B - 35 mg REMD-477 | Summary of REMD-477 Plasma Concentrations | Baseline (Day 1 Pre-dose) | 0 ng/mL | Geometric Coefficient of Variation 0 |
| Part B - 35 mg REMD-477 | Summary of REMD-477 Plasma Concentrations | Week 5 | 11000 ng/mL | Geometric Coefficient of Variation 33.3 |
Secondary
Summary of the Product of Average Daily 24-h Glucose Ratio and Daily Insulin Use Ratio (Day 78 [Week 12]/Baseline)
The product of the ratio of average glucose (Week 12/Baseline) and ratio of average insulin use (Week 12/Baseline).
Time frame: Baseline and week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A - 35 mg REMD-477 | Summary of the Product of Average Daily 24-h Glucose Ratio and Daily Insulin Use Ratio (Day 78 [Week 12]/Baseline) | 0.86 Ratio | Standard Error 0.41 |
| Part A - 70 mg REMD-477 | Summary of the Product of Average Daily 24-h Glucose Ratio and Daily Insulin Use Ratio (Day 78 [Week 12]/Baseline) | 0.81 Ratio | Standard Error 0.041 |
| Part A - Matching Placebo | Summary of the Product of Average Daily 24-h Glucose Ratio and Daily Insulin Use Ratio (Day 78 [Week 12]/Baseline) | 0.98 Ratio | Standard Error 0.049 |
| Part B - 35 mg REMD-477 | Summary of the Product of Average Daily 24-h Glucose Ratio and Daily Insulin Use Ratio (Day 78 [Week 12]/Baseline) | 0.88 Ratio | Standard Error 0.082 |
| Part B - 70 mg REMD-477 | Summary of the Product of Average Daily 24-h Glucose Ratio and Daily Insulin Use Ratio (Day 78 [Week 12]/Baseline) | 0.89 Ratio | Standard Error 0.086 |
| Part B - Matching Placebo | Summary of the Product of Average Daily 24-h Glucose Ratio and Daily Insulin Use Ratio (Day 78 [Week 12]/Baseline) | 0.95 Ratio | Standard Error 0.077 |