Familial Partial Lipodystrophy, Metabolic Abnormalities
Conditions
Brief summary
Two cohorts are being studied based on leptin levels. Cohort A is composed of patients with baseline leptin \<8.0 ng/mL and Cohort B is composed of patients with baseline leptin 8.0 to ≤20.0 ng/mL The primary objectives will be evaluated for patients in Cohort A only: * To evaluate the effect of REGN4461 on fasting triglycerides (TG) in patients with elevated baseline fasting TG * To evaluate the effect of REGN4461 on hyperglycemia in patients with elevated baseline Hemoglobin A1c (HbA1c) The following secondary objectives of the study will be evaluated for Cohort B and for the combined set of Cohorts A plus B: * To evaluate the effect of REGN4461 on fasting TG levels in patients with hypertriglyceridemia * To evaluate the effect of REGN4461 on glycemic control in patients with hyperglycemia The following secondary objectives of the study will be evaluated for Cohorts A and B separately, and for the combined set of Cohorts A plus B: * To evaluate the effect of REGN4461 on liver fat in patients with hepatic steatosis * To evaluate the effect of REGN4461 on hunger * To evaluate safety and tolerability of REGN4461 * To characterize the concentration profile of REGN4461 over time * To assess immunogenicity to REGN4461
Interventions
DRUGREGN4461
Intravenous (IV) infusion loading dose followed by subcutaneous (SC) injection weekly (QW).
DRUGMatching Placebo
Intravenous (IV) infusion loading dose followed by subcutaneous (SC) injection weekly (QW).
Sponsors
Regeneron Pharmaceuticals
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 No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Clinical diagnosis of familial partial lipodystrophy as defined in the protocol * Fasting leptin level ≤20.0 ng/ml, as determined during the screening period * Presence of significant metabolic abnormalities related to glucose and triglycerides (TGs) as defined in the protocol * Stable body weight within the 3 months prior to screening (no gain or loss of \>5% current weight) * Stable diet during the past 3 months defined as no major change in macronutrient composition (eg, starting or stopping diets such as Atkins, Paleo, Vegetarianism, Veganism) * No clinically meaningful change in medication regimen in the 3 months prior to screening as defined in the protocol Key
Exclusion criteria
* Treatment with metreleptin within 3 months of the screening visit * Patients with a diagnosis of generalized lipodystrophy * Patients with a diagnosis of acquired lipodystrophy * Pregnant or breastfeeding women NOTE: Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline to Week 12 in Fasting Serum Triglyceride (TG) (Cohort A) | Baseline to week 12 | Percentage change in fasting serum TG was reported for participants with elevated baseline fasting TG (\> 200 mg/dL) and with baseline leptin \< 8.0 ng/mL (Cohort A). |
| Change From Baseline to Week 12 in Hemoglobin A1c (HbA1c) (Cohort A) | Baseline to week 12 | Change in HbA1c was reported for participants with elevated baseline HbA1c (\> 7.0%) and with baseline leptin \< 8.0 ng/mL (Cohort A). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline to Week 12 in Fasting Serum TG (Cohorts B and A + B) | Baseline to week 12 | Percent change in fasting serum TG was reported for participants with elevated baseline fasting TG (\>200 mg/dL) in Cohort B and Cohorts A + B. |
| Change From Baseline to Week 12 in HbA1c (Cohorts B and A + B) | Baseline to week 12 | Change in HbA1c was reported for participants with elevated baseline HbA1c (\>7.0%) in Cohort B and Cohorts A + B. |
| Percent Change From Baseline to Weeks 12 and 24 in Fasting Serum TG (Study Arm 1) | Baseline, Week 12, Week 24 | Percent change in fasting serum TG was reported for participants in Study Arm 1. |
| Percent Change From Baseline to Weeks 12 and 24 in Fasting Serum TG (Study Arm 2) | Baseline, Week 12, Week 24 | Percent change in fasting serum TG was reported for participants in Study Arm 2. |
| Change From Baseline to Weeks 12 and 24 in HbA1c (Study Arm 1) | Baseline, Week 12, Week 24 | Change from baseline in HbA1c was reported for participants in Study Arm 1. |
| Change From Baseline to Weeks 12 and 24 in HbA1c (Study Arm 2) | Baseline, Week 12, Week 24 | Change from baseline in HbA1c was reported for participants in Study Arm 2. |
| Change From Baseline to Weeks 12 and 24 in Fasting Glucose (Study Arm 1) | Baseline, Week 12, Week 24 | Change from baseline in fasting glucose was reported for participants in Study Arm 1. |
| Change From Baseline to Weeks 12 and 24 in Fasting Glucose (Study Arm 2) | Baseline, Week 12, Week 24 | Change from baseline in fasting glucose was reported for participants in Study Arm 2. |
| Percent Change From Baseline to Weeks 12 and 24 in Liver Fat Magnetic Resonance Imaging-derived Proton Density Fat Fraction (MRI-PDFF) (Study Arm 1) | Baseline, Week 12, Week 24 | Percent change from baseline in MRI-PDFF was reported for participants with baseline MRI-PDFF ≥8.5% in Study Arm 1. |
| Percent Change From Baseline to Weeks 12 and 24 in Liver Fat MRI-PDFF (Study Arm 2) | Baseline, Week 12, Week 24 | Percent change from baseline in MRI-PDFF was reported for participants with baseline liver fat MRI-PDFF ≥8.5% in Study Arm 2. |
| Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Highest Hunger Score | Baseline, Week 12, Week 24 | The daily lipodystrophy hunger questionnaire was developed to assess hunger related behaviors among patients with lipodystrophy. The highest hunger score asked participants to rate their highest hunger that day on a scale from 0 to 4, with higher scores representing the higher perceived hunger. A negative change from baseline indicated a reduction in perceived hunger. |
| Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Lowest Hunger Score | Baseline, Week 12, Week 24 | The daily lipodystrophy hunger questionnaire was developed to assess hunger related behaviors among patients with lipodystrophy. The lowest hunger score asked participants to rate their lowest hunger that day on a scale from 0 to 4, with higher scores indicating higher perceived hunger. A negative change from baseline score indicated a reduction in perceived lowest hunger. |
| Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Felt Hungry Score | Baseline, Week 12, Week 24 | The daily lipodystrophy hunger questionnaire was developed to assess hunger related behaviors among participants with lipodystrophy. The felt hungry score asked how much time participants felt hunger that day on a scale from 0 to 4, with higher scores indicating more time feeling hungry. A negative change from baseline score indicated a reduction in time spent feeling hungry. |
| Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Fullness Score | Baseline, Week 12, Week 24 | The daily lipodystrophy hunger questionnaire was developed to assess hunger related behaviors among patients with lipodystrophy. The fullness score asked participants to rate how often they felt full after eating that day on a scale from 0 to 4, with higher scores indicating higher feeling of fullness. A negative change from baseline indicated a reduced feeling of fullness. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Up to Day 169 | — |
| Concentrations of REGN4461 in Serum | Weeks 0, 1, 2, 3, 4, 5, 6, 9, 12, 13, 14, 15, 16, 17, 18, 21, 28, 32 and 36. Weeks 0 and 12 collected pre- and post-dose. All other time points were only pre-dose. | — |
| Number of Participants With Treatment-emergent Anti-drug Antibody (ADA) Response | Up to Day 281 | — |
Countries
France, Spain, Turkey (Türkiye), United States
Participant flow
Pre-assignment details
A total of 66 participants were screened, of whom 20 were randomized and received study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Arm 1 Cohort A: Placebo to REGN4461 Participants randomized to Arm 1 received placebo for 12 weeks during the DBTP followed by crossover to REGN4461 treatment for 12 weeks during the SBTP. | 6 |
| Arm 2 Cohort A: REGN4461 to REGN4461 Participants randomized to Arm 2 received REGN4461 treatment for 12 weeks during the DBTP followed by an additional 12 weeks of REGN4461 treatment during the SBTP. | 6 |
| Arm 1 Cohort B: Placebo to REGN4461 Participants randomized to Arm 1 received placebo for 12 weeks during the DBTP followed by crossover to REGN4461 treatment for 12 weeks during the SBTP. | 4 |
| Arm 2 Cohort B: REGN4461 to REGN4461 Participants randomized to Arm 2 received REGN4461 treatment for 12 weeks during the DBTP followed by an additional 12 weeks of REGN4461 treatment during the SBTP. | 4 |
| Total | 20 |
Baseline characteristics
| Characteristic | Arm 1 Cohort A: Placebo to REGN4461 | Total | Arm 2 Cohort B: REGN4461 to REGN4461 | Arm 1 Cohort B: Placebo to REGN4461 | Arm 2 Cohort A: REGN4461 to REGN4461 |
|---|---|---|---|---|---|
| Age, Continuous | 40.5 years STANDARD_DEVIATION 16.79 | 43.0 years STANDARD_DEVIATION 13.4 | 40.3 years STANDARD_DEVIATION 12.82 | 48.0 years STANDARD_DEVIATION 11.97 | 43.8 years STANDARD_DEVIATION 13.47 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 20 Participants | 4 Participants | 4 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Fasting Triglycerides Serum Concentration | 1100.9 milligrams per deciliter (mg/dL) | 698.3 milligrams per deciliter (mg/dL) | 336.2 milligrams per deciliter (mg/dL) | 675.0 milligrams per deciliter (mg/dL) | 737.8 milligrams per deciliter (mg/dL) |
| Hemoglobin A1c (HbA1c) | 8.8 percentage of glycated hemoglobin STANDARD_DEVIATION 1.62 | 8.2 percentage of glycated hemoglobin STANDARD_DEVIATION 1.68 | 8.6 percentage of glycated hemoglobin STANDARD_DEVIATION 2.06 | 6.9 percentage of glycated hemoglobin STANDARD_DEVIATION 0.91 | 8.2 percentage of glycated hemoglobin STANDARD_DEVIATION 1.76 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 18 Participants | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Female | 5 Participants | 18 Participants | 4 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants |
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 | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 4 | 0 / 4 | 0 / 5 | 0 / 6 | 0 / 3 | 0 / 4 |
| other Total, other adverse events | 6 / 6 | 6 / 6 | 4 / 4 | 4 / 4 | 3 / 5 | 5 / 6 | 3 / 3 | 4 / 4 |
| serious Total, serious adverse events | 1 / 6 | 1 / 6 | 1 / 4 | 0 / 4 | 1 / 5 | 1 / 6 | 0 / 3 | 0 / 4 |
Outcome results
Primary
Change From Baseline to Week 12 in Hemoglobin A1c (HbA1c) (Cohort A)
Change in HbA1c was reported for participants with elevated baseline HbA1c (\> 7.0%) and with baseline leptin \< 8.0 ng/mL (Cohort A).
Time frame: Baseline to week 12
Population: The FAS included all randomized participants who received any study drug in the DBTP and had at least 1 post-baseline assessment. Here, Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 Cohort A: Placebo to REGN4461 | Change From Baseline to Week 12 in Hemoglobin A1c (HbA1c) (Cohort A) | -0.05 percentage of glycated hemoglobin | Standard Deviation 0.451 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Change From Baseline to Week 12 in Hemoglobin A1c (HbA1c) (Cohort A) | -1.08 percentage of glycated hemoglobin | Standard Deviation 1.108 |
Primary
Percent Change From Baseline to Week 12 in Fasting Serum Triglyceride (TG) (Cohort A)
Percentage change in fasting serum TG was reported for participants with elevated baseline fasting TG (\> 200 mg/dL) and with baseline leptin \< 8.0 ng/mL (Cohort A).
Time frame: Baseline to week 12
Population: The Full Analysis Set (FAS) included all randomized participants who received any study drug in the double-blind treatment period (DBTP) and had at least 1 post-baseline assessment. Here, Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 Cohort A: Placebo to REGN4461 | Percent Change From Baseline to Week 12 in Fasting Serum Triglyceride (TG) (Cohort A) | -11.30 percent change | Standard Deviation 46.306 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Percent Change From Baseline to Week 12 in Fasting Serum Triglyceride (TG) (Cohort A) | -38.97 percent change | Standard Deviation 16.998 |
Secondary
Change From Baseline to Week 12 in HbA1c (Cohorts B and A + B)
Change in HbA1c was reported for participants with elevated baseline HbA1c (\>7.0%) in Cohort B and Cohorts A + B.
Time frame: Baseline to week 12
Population: The FAS included all randomized participants who received any study drug in the DBTP and had at least 1 post-baseline assessment. Here, Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 Cohort A: Placebo to REGN4461 | Change From Baseline to Week 12 in HbA1c (Cohorts B and A + B) | -0.20 percentage of glycated hemoglobin | Standard Deviation 0.283 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Change From Baseline to Week 12 in HbA1c (Cohorts B and A + B) | -0.90 percentage of glycated hemoglobin | Standard Deviation 0.964 |
| Arm 1 Combined Cohort A + B: Placebo to REGN4461 | Change From Baseline to Week 12 in HbA1c (Cohorts B and A + B) | -0.10 percentage of glycated hemoglobin | Standard Deviation 0.379 |
| Arm 2 Combined Cohort A + B: REGN4461 to REGN4461 | Change From Baseline to Week 12 in HbA1c (Cohorts B and A + B) | -1.01 percentage of glycated hemoglobin | Standard Deviation 0.988 |
Secondary
Change From Baseline to Weeks 12 and 24 in Fasting Glucose (Study Arm 1)
Change from baseline in fasting glucose was reported for participants in Study Arm 1.
Time frame: Baseline, Week 12, Week 24
Population: The FAS included all randomized participants who received any study drug in the DBTP and had at least 1 post-baseline assessment. Here, Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure, and Number analyzed is the number of participants evaluated at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 Cohort A: Placebo to REGN4461 | Change From Baseline to Weeks 12 and 24 in Fasting Glucose (Study Arm 1) | Week 24 | 7.2 milligrams per deciliter (mg/dL) | Standard Deviation 29.65 |
| Arm 1 Cohort A: Placebo to REGN4461 | Change From Baseline to Weeks 12 and 24 in Fasting Glucose (Study Arm 1) | Week 12 | 4.8 milligrams per deciliter (mg/dL) | Standard Deviation 29.55 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Change From Baseline to Weeks 12 and 24 in Fasting Glucose (Study Arm 1) | Week 24 | -15.5 milligrams per deciliter (mg/dL) | Standard Deviation 6.36 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Change From Baseline to Weeks 12 and 24 in Fasting Glucose (Study Arm 1) | Week 12 | 0.0 milligrams per deciliter (mg/dL) | Standard Deviation 60.37 |
| Arm 1 Combined Cohort A + B: Placebo to REGN4461 | Change From Baseline to Weeks 12 and 24 in Fasting Glucose (Study Arm 1) | Week 12 | 2.7 milligrams per deciliter (mg/dL) | Standard Deviation 42.54 |
| Arm 1 Combined Cohort A + B: Placebo to REGN4461 | Change From Baseline to Weeks 12 and 24 in Fasting Glucose (Study Arm 1) | Week 24 | 0.7 milligrams per deciliter (mg/dL) | Standard Deviation 26.75 |
Secondary
Change From Baseline to Weeks 12 and 24 in Fasting Glucose (Study Arm 2)
Change from baseline in fasting glucose was reported for participants in Study Arm 2.
Time frame: Baseline, Week 12, Week 24
Population: The FAS included all randomized participants who received any study drug in the DBTP and had at least 1 post-baseline assessment. Here, Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure, and Number analyzed is the number of participants evaluated at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 Cohort A: Placebo to REGN4461 | Change From Baseline to Weeks 12 and 24 in Fasting Glucose (Study Arm 2) | Week 12 | -5.2 mg/dL | Standard Deviation 36.55 |
| Arm 1 Cohort A: Placebo to REGN4461 | Change From Baseline to Weeks 12 and 24 in Fasting Glucose (Study Arm 2) | Week 24 | 1.8 mg/dL | Standard Deviation 26.35 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Change From Baseline to Weeks 12 and 24 in Fasting Glucose (Study Arm 2) | Week 12 | -19.5 mg/dL | Standard Deviation 22.87 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Change From Baseline to Weeks 12 and 24 in Fasting Glucose (Study Arm 2) | Week 24 | -12.3 mg/dL | Standard Deviation 58.59 |
| Arm 1 Combined Cohort A + B: Placebo to REGN4461 | Change From Baseline to Weeks 12 and 24 in Fasting Glucose (Study Arm 2) | Week 12 | -10.9 mg/dL | Standard Deviation 31.17 |
| Arm 1 Combined Cohort A + B: Placebo to REGN4461 | Change From Baseline to Weeks 12 and 24 in Fasting Glucose (Study Arm 2) | Week 24 | -5.3 mg/dL | Standard Deviation 42.71 |
Secondary
Change From Baseline to Weeks 12 and 24 in HbA1c (Study Arm 1)
Change from baseline in HbA1c was reported for participants in Study Arm 1.
Time frame: Baseline, Week 12, Week 24
Population: The FAS included all randomized participants who received any study drug in the DBTP and had at least 1 post-baseline assessment. Here, Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure, and Number analyzed is the number of participants evaluated at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 Cohort A: Placebo to REGN4461 | Change From Baseline to Weeks 12 and 24 in HbA1c (Study Arm 1) | Week 24 | -0.78 percentage of glycated hemoglobin | Standard Deviation 0.694 |
| Arm 1 Cohort A: Placebo to REGN4461 | Change From Baseline to Weeks 12 and 24 in HbA1c (Study Arm 1) | Week 12 | -0.10 percentage of glycated hemoglobin | Standard Deviation 0.406 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Change From Baseline to Weeks 12 and 24 in HbA1c (Study Arm 1) | Week 24 | 0.13 percentage of glycated hemoglobin | Standard Deviation 0.802 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Change From Baseline to Weeks 12 and 24 in HbA1c (Study Arm 1) | Week 12 | 0.13 percentage of glycated hemoglobin | Standard Deviation 0.427 |
| Arm 1 Combined Cohort A + B: Placebo to REGN4461 | Change From Baseline to Weeks 12 and 24 in HbA1c (Study Arm 1) | Week 12 | 0.00 percentage of glycated hemoglobin | Standard Deviation 0.406 |
| Arm 1 Combined Cohort A + B: Placebo to REGN4461 | Change From Baseline to Weeks 12 and 24 in HbA1c (Study Arm 1) | Week 24 | -0.44 percentage of glycated hemoglobin | Standard Deviation 0.826 |
Secondary
Change From Baseline to Weeks 12 and 24 in HbA1c (Study Arm 2)
Change from baseline in HbA1c was reported for participants in Study Arm 2.
Time frame: Baseline, Week 12, Week 24
Population: The FAS included all randomized participants who received any study drug in the DBTP and had at least 1 post-baseline assessment. Here, Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure, and Number analyzed is the number of participants evaluated at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 Cohort A: Placebo to REGN4461 | Change From Baseline to Weeks 12 and 24 in HbA1c (Study Arm 2) | Week 12 | -0.92 percentage of glycated hemoglobin | Standard Deviation 1.068 |
| Arm 1 Cohort A: Placebo to REGN4461 | Change From Baseline to Weeks 12 and 24 in HbA1c (Study Arm 2) | Week 24 | -0.98 percentage of glycated hemoglobin | Standard Deviation 1.357 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Change From Baseline to Weeks 12 and 24 in HbA1c (Study Arm 2) | Week 12 | -0.78 percentage of glycated hemoglobin | Standard Deviation 0.826 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Change From Baseline to Weeks 12 and 24 in HbA1c (Study Arm 2) | Week 24 | -0.50 percentage of glycated hemoglobin | Standard Deviation 1.068 |
| Arm 1 Combined Cohort A + B: Placebo to REGN4461 | Change From Baseline to Weeks 12 and 24 in HbA1c (Study Arm 2) | Week 12 | -0.86 percentage of glycated hemoglobin | Standard Deviation 0.931 |
| Arm 1 Combined Cohort A + B: Placebo to REGN4461 | Change From Baseline to Weeks 12 and 24 in HbA1c (Study Arm 2) | Week 24 | -0.77 percentage of glycated hemoglobin | Standard Deviation 1.188 |
Secondary
Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Felt Hungry Score
The daily lipodystrophy hunger questionnaire was developed to assess hunger related behaviors among participants with lipodystrophy. The felt hungry score asked how much time participants felt hunger that day on a scale from 0 to 4, with higher scores indicating more time feeling hungry. A negative change from baseline score indicated a reduction in time spent feeling hungry.
Time frame: Baseline, Week 12, Week 24
Population: The FAS included all randomized participants who received any study drug in the DBTP and had at least 1 post-baseline assessment. Here, Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure, and Number analyzed is the number of participants evaluated at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 Cohort A: Placebo to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Felt Hungry Score | Week 12 | 0.248 score on a scale | Standard Deviation 0.8642 |
| Arm 1 Cohort A: Placebo to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Felt Hungry Score | Week 24 | 0.016 score on a scale | Standard Deviation 0.3932 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Felt Hungry Score | Week 24 | 0.120 score on a scale | Standard Deviation 0.4374 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Felt Hungry Score | Week 12 | -0.550 score on a scale | Standard Deviation 0.5334 |
| Arm 1 Combined Cohort A + B: Placebo to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Felt Hungry Score | Week 12 | -0.168 score on a scale | Standard Deviation 0.29 |
| Arm 1 Combined Cohort A + B: Placebo to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Felt Hungry Score | Week 24 | -0.183 score on a scale | Standard Deviation 0.0603 |
| Arm 2 Combined Cohort A + B: REGN4461 to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Felt Hungry Score | Week 12 | 0.008 score on a scale | Standard Deviation 0.9139 |
| Arm 2 Combined Cohort A + B: REGN4461 to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Felt Hungry Score | Week 24 | -0.138 score on a scale | Standard Deviation 0.6595 |
| Arm 1 Combined Cohort A + B: Placebo to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Felt Hungry Score | Week 12 | 0.082 score on a scale | Standard Deviation 0.6993 |
| Arm 1 Combined Cohort A + B: Placebo to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Felt Hungry Score | Week 24 | -0.059 score on a scale | Standard Deviation 0.3163 |
| Arm 2 Combined Cohort A + B: REGN4461 to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Felt Hungry Score | Week 24 | 0.006 score on a scale | Standard Deviation 0.5265 |
| Arm 2 Combined Cohort A + B: REGN4461 to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Felt Hungry Score | Week 12 | -0.327 score on a scale | Standard Deviation 0.7206 |
Secondary
Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Fullness Score
The daily lipodystrophy hunger questionnaire was developed to assess hunger related behaviors among patients with lipodystrophy. The fullness score asked participants to rate how often they felt full after eating that day on a scale from 0 to 4, with higher scores indicating higher feeling of fullness. A negative change from baseline indicated a reduced feeling of fullness.
Time frame: Baseline, Week 12, Week 24
Population: The FAS included all randomized participants who received any study drug in the DBTP and had at least 1 post-baseline assessment. Here, Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure, and Number analyzed is the number of participants evaluated at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 Cohort A: Placebo to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Fullness Score | Week 12 | 0.063 score on a scale | Standard Deviation 1.1988 |
| Arm 1 Cohort A: Placebo to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Fullness Score | Week 24 | -0.182 score on a scale | Standard Deviation 0.6474 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Fullness Score | Week 24 | 0.012 score on a scale | Standard Deviation 0.6474 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Fullness Score | Week 12 | -0.267 score on a scale | Standard Deviation 0.5381 |
| Arm 1 Combined Cohort A + B: Placebo to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Fullness Score | Week 24 | -1.193 score on a scale | Standard Deviation 0.663 |
| Arm 1 Combined Cohort A + B: Placebo to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Fullness Score | Week 12 | -1.180 score on a scale | Standard Deviation 0.3764 |
| Arm 2 Combined Cohort A + B: REGN4461 to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Fullness Score | Week 24 | -0.178 score on a scale | Standard Deviation 0.8032 |
| Arm 2 Combined Cohort A + B: REGN4461 to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Fullness Score | Week 12 | -0.535 score on a scale | Standard Deviation 0.5736 |
| Arm 1 Combined Cohort A + B: Placebo to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Fullness Score | Week 24 | -0.561 score on a scale | Standard Deviation 0.7994 |
| Arm 1 Combined Cohort A + B: Placebo to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Fullness Score | Week 12 | -0.434 score on a scale | Standard Deviation 1.1216 |
| Arm 2 Combined Cohort A + B: REGN4461 to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Fullness Score | Week 12 | -0.374 score on a scale | Standard Deviation 0.5383 |
| Arm 2 Combined Cohort A + B: REGN4461 to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Fullness Score | Week 24 | -0.072 score on a scale | Standard Deviation 0.6793 |
Secondary
Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Highest Hunger Score
The daily lipodystrophy hunger questionnaire was developed to assess hunger related behaviors among patients with lipodystrophy. The highest hunger score asked participants to rate their highest hunger that day on a scale from 0 to 4, with higher scores representing the higher perceived hunger. A negative change from baseline indicated a reduction in perceived hunger.
Time frame: Baseline, Week 12, Week 24
Population: The FAS included all randomized participants who received any study drug in the DBTP and had at least 1 post-baseline assessment. Here, Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure, and Number analyzed is the number of participants evaluated at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 Cohort A: Placebo to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Highest Hunger Score | Week 24 | -0.330 score on a scale | Standard Deviation 0.3684 |
| Arm 1 Cohort A: Placebo to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Highest Hunger Score | Week 12 | -0.060 score on a scale | Standard Deviation 0.9009 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Highest Hunger Score | Week 24 | -0.018 score on a scale | Standard Deviation 0.6228 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Highest Hunger Score | Week 12 | -0.538 score on a scale | Standard Deviation 0.4679 |
| Arm 1 Combined Cohort A + B: Placebo to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Highest Hunger Score | Week 12 | -0.240 score on a scale | Standard Deviation 0.2483 |
| Arm 1 Combined Cohort A + B: Placebo to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Highest Hunger Score | Week 24 | -0.383 score on a scale | Standard Deviation 0.155 |
| Arm 2 Combined Cohort A + B: REGN4461 to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Highest Hunger Score | Week 24 | -0.285 score on a scale | Standard Deviation 0.618 |
| Arm 2 Combined Cohort A + B: REGN4461 to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Highest Hunger Score | Week 12 | -0.415 score on a scale | Standard Deviation 0.7539 |
| Arm 1 Combined Cohort A + B: Placebo to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Highest Hunger Score | Week 12 | -0.132 score on a scale | Standard Deviation 0.6929 |
| Arm 1 Combined Cohort A + B: Placebo to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Highest Hunger Score | Week 24 | -0.350 score on a scale | Standard Deviation 0.2919 |
| Arm 2 Combined Cohort A + B: REGN4461 to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Highest Hunger Score | Week 12 | -0.489 score on a scale | Standard Deviation 0.5614 |
| Arm 2 Combined Cohort A + B: REGN4461 to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Highest Hunger Score | Week 24 | -0.137 score on a scale | Standard Deviation 0.5975 |
Secondary
Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Lowest Hunger Score
The daily lipodystrophy hunger questionnaire was developed to assess hunger related behaviors among patients with lipodystrophy. The lowest hunger score asked participants to rate their lowest hunger that day on a scale from 0 to 4, with higher scores indicating higher perceived hunger. A negative change from baseline score indicated a reduction in perceived lowest hunger.
Time frame: Baseline, Week 12, Week 24
Population: The FAS included all randomized participants who received any study drug in the DBTP and had at least 1 post-baseline assessment. Here, Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure, and Number analyzed is the number of participants evaluated at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 Cohort A: Placebo to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Lowest Hunger Score | Week 24 | -0.128 score on a scale | Standard Deviation 0.0622 |
| Arm 1 Cohort A: Placebo to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Lowest Hunger Score | Week 12 | 0.185 score on a scale | Standard Deviation 0.8013 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Lowest Hunger Score | Week 24 | 0.046 score on a scale | Standard Deviation 0.6776 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Lowest Hunger Score | Week 12 | -0.475 score on a scale | Standard Deviation 0.463 |
| Arm 1 Combined Cohort A + B: Placebo to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Lowest Hunger Score | Week 12 | -0.338 score on a scale | Standard Deviation 0.4287 |
| Arm 1 Combined Cohort A + B: Placebo to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Lowest Hunger Score | Week 24 | -0.103 score on a scale | Standard Deviation 0.223 |
| Arm 2 Combined Cohort A + B: REGN4461 to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Lowest Hunger Score | Week 24 | 0.308 score on a scale | Standard Deviation 0.9603 |
| Arm 2 Combined Cohort A + B: REGN4461 to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Lowest Hunger Score | Week 12 | -0.173 score on a scale | Standard Deviation 0.3625 |
| Arm 1 Combined Cohort A + B: Placebo to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Lowest Hunger Score | Week 12 | -0.024 score on a scale | Standard Deviation 0.7006 |
| Arm 1 Combined Cohort A + B: Placebo to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Lowest Hunger Score | Week 24 | -0.119 score on a scale | Standard Deviation 0.1288 |
| Arm 2 Combined Cohort A + B: REGN4461 to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Lowest Hunger Score | Week 12 | -0.354 score on a scale | Standard Deviation 0.4328 |
| Arm 2 Combined Cohort A + B: REGN4461 to REGN4461 | Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Lowest Hunger Score | Week 24 | 0.162 score on a scale | Standard Deviation 0.771 |
Secondary
Concentrations of REGN4461 in Serum
Time frame: Weeks 0, 1, 2, 3, 4, 5, 6, 9, 12, 13, 14, 15, 16, 17, 18, 21, 28, 32 and 36. Weeks 0 and 12 collected pre- and post-dose. All other time points were only pre-dose.
Population: The PK analysis set was defined as all randomized participants who received any study drug and have at least 1 non-missing measurement of REGN4461 concentration following the first dose of study drug. Here, Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure, and Number analyzed is the number of participants evaluated at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 Cohort A: Placebo to REGN4461 | Concentrations of REGN4461 in Serum | Week 0 (pre-dose) | 0 milligrams per liter (mg/L) | Standard Deviation 0 |
| Arm 1 Cohort A: Placebo to REGN4461 | Concentrations of REGN4461 in Serum | Week 0 (post-dose) | 0 milligrams per liter (mg/L) | Standard Deviation 0 |
| Arm 1 Cohort A: Placebo to REGN4461 | Concentrations of REGN4461 in Serum | Week 1 (pre-dose) | 0 milligrams per liter (mg/L) | Standard Deviation 0 |
| Arm 1 Cohort A: Placebo to REGN4461 | Concentrations of REGN4461 in Serum | Week 2 (pre-dose) | 0 milligrams per liter (mg/L) | Standard Deviation 0 |
| Arm 1 Cohort A: Placebo to REGN4461 | Concentrations of REGN4461 in Serum | Week 3 (pre-dose) | 0 milligrams per liter (mg/L) | Standard Deviation 0 |
| Arm 1 Cohort A: Placebo to REGN4461 | Concentrations of REGN4461 in Serum | Week 4 (pre-dose) | 0 milligrams per liter (mg/L) | Standard Deviation 0 |
| Arm 1 Cohort A: Placebo to REGN4461 | Concentrations of REGN4461 in Serum | Week 5 (pre-dose) | 0 milligrams per liter (mg/L) | Standard Deviation 0 |
| Arm 1 Cohort A: Placebo to REGN4461 | Concentrations of REGN4461 in Serum | Week 6 (pre-dose) | 0 milligrams per liter (mg/L) | Standard Deviation 0 |
| Arm 1 Cohort A: Placebo to REGN4461 | Concentrations of REGN4461 in Serum | Week 9 (pre-dose) | 0 milligrams per liter (mg/L) | Standard Deviation 0 |
| Arm 1 Cohort A: Placebo to REGN4461 | Concentrations of REGN4461 in Serum | Week 12 (pre-dose) | 0 milligrams per liter (mg/L) | Standard Deviation 0 |
| Arm 1 Cohort A: Placebo to REGN4461 | Concentrations of REGN4461 in Serum | Week 12 (post-dose) | 252 milligrams per liter (mg/L) | Standard Deviation 50.7 |
| Arm 1 Cohort A: Placebo to REGN4461 | Concentrations of REGN4461 in Serum | Week 13 (pre-dose) | 62.4 milligrams per liter (mg/L) | Standard Deviation 17.5 |
| Arm 1 Cohort A: Placebo to REGN4461 | Concentrations of REGN4461 in Serum | Week 14 (pre-dose) | 56.6 milligrams per liter (mg/L) | Standard Deviation 17.6 |
| Arm 1 Cohort A: Placebo to REGN4461 | Concentrations of REGN4461 in Serum | Week 15 (pre-dose) | 64.2 milligrams per liter (mg/L) | Standard Deviation 29.6 |
| Arm 1 Cohort A: Placebo to REGN4461 | Concentrations of REGN4461 in Serum | Week 16 (pre-dose) | 68.8 milligrams per liter (mg/L) | Standard Deviation 24.3 |
| Arm 1 Cohort A: Placebo to REGN4461 | Concentrations of REGN4461 in Serum | Week 17 (pre-dose) | 73.4 milligrams per liter (mg/L) | Standard Deviation 30.8 |
| Arm 1 Cohort A: Placebo to REGN4461 | Concentrations of REGN4461 in Serum | Week 18 (pre-dose) | 75.1 milligrams per liter (mg/L) | Standard Deviation 27.1 |
| Arm 1 Cohort A: Placebo to REGN4461 | Concentrations of REGN4461 in Serum | Week 21 (pre-dose) | 89.3 milligrams per liter (mg/L) | Standard Deviation 40 |
| Arm 1 Cohort A: Placebo to REGN4461 | Concentrations of REGN4461 in Serum | Week 28 (pre-dose) | 10.9 milligrams per liter (mg/L) | Standard Deviation 12 |
| Arm 1 Cohort A: Placebo to REGN4461 | Concentrations of REGN4461 in Serum | Week 32 (pre-dose) | 0.0663 milligrams per liter (mg/L) | Standard Deviation 0.0705 |
| Arm 1 Cohort A: Placebo to REGN4461 | Concentrations of REGN4461 in Serum | Week 36 (pre-dose) | 0.0110 milligrams per liter (mg/L) | Standard Deviation 0.033 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Concentrations of REGN4461 in Serum | Week 12 (post-dose) | 87.6 milligrams per liter (mg/L) | Standard Deviation 49.7 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Concentrations of REGN4461 in Serum | Week 0 (pre-dose) | 0 milligrams per liter (mg/L) | Standard Deviation 0 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Concentrations of REGN4461 in Serum | Week 28 (pre-dose) | 16.0 milligrams per liter (mg/L) | Standard Deviation 23.4 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Concentrations of REGN4461 in Serum | Week 0 (post-dose) | 232 milligrams per liter (mg/L) | Standard Deviation 83.8 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Concentrations of REGN4461 in Serum | Week 13 (pre-dose) | 97.6 milligrams per liter (mg/L) | Standard Deviation 68.6 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Concentrations of REGN4461 in Serum | Week 1 (pre-dose) | 64.3 milligrams per liter (mg/L) | Standard Deviation 24.9 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Concentrations of REGN4461 in Serum | Week 18 (pre-dose) | 95.0 milligrams per liter (mg/L) | Standard Deviation 79.3 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Concentrations of REGN4461 in Serum | Week 2 (pre-dose) | 52.5 milligrams per liter (mg/L) | Standard Deviation 13.3 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Concentrations of REGN4461 in Serum | Week 14 (pre-dose) | 92.8 milligrams per liter (mg/L) | Standard Deviation 68 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Concentrations of REGN4461 in Serum | Week 3 (pre-dose) | 60.2 milligrams per liter (mg/L) | Standard Deviation 19 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Concentrations of REGN4461 in Serum | Week 36 (pre-dose) | 0.0373 milligrams per liter (mg/L) | Standard Deviation 0.0788 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Concentrations of REGN4461 in Serum | Week 4 (pre-dose) | 58.8 milligrams per liter (mg/L) | Standard Deviation 23.8 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Concentrations of REGN4461 in Serum | Week 15 (pre-dose) | 90.5 milligrams per liter (mg/L) | Standard Deviation 59.1 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Concentrations of REGN4461 in Serum | Week 5 (pre-dose) | 62.0 milligrams per liter (mg/L) | Standard Deviation 36.1 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Concentrations of REGN4461 in Serum | Week 21 (pre-dose) | 72.9 milligrams per liter (mg/L) | Standard Deviation 51.4 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Concentrations of REGN4461 in Serum | Week 6 (pre-dose) | 68.8 milligrams per liter (mg/L) | Standard Deviation 38.8 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Concentrations of REGN4461 in Serum | Week 16 (pre-dose) | 103 milligrams per liter (mg/L) | Standard Deviation 76.4 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Concentrations of REGN4461 in Serum | Week 9 (pre-dose) | 79.6 milligrams per liter (mg/L) | Standard Deviation 49.2 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Concentrations of REGN4461 in Serum | Week 32 (pre-dose) | 0.189 milligrams per liter (mg/L) | Standard Deviation 0.281 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Concentrations of REGN4461 in Serum | Week 12 (pre-dose) | 87.1 milligrams per liter (mg/L) | Standard Deviation 57.8 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Concentrations of REGN4461 in Serum | Week 17 (pre-dose) | 92.1 milligrams per liter (mg/L) | Standard Deviation 73.3 |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: Up to Day 169
Population: The DB SAF included all participants who received any double-blind study drug in DBTP. The single-blind safety analysis set (SB SAF) included all randomized participants who received any single-blind study drug in the single-blind treatment period (SBTP).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1 Cohort A: Placebo to REGN4461 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 4 Participants |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 5 Participants |
| Arm 1 Combined Cohort A + B: Placebo to REGN4461 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 4 Participants |
| Arm 2 Combined Cohort A + B: REGN4461 to REGN4461 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 4 Participants |
| Arm 1 Combined Cohort A + B: Placebo to REGN4461 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 8 Participants |
| Arm 2 Combined Cohort A + B: REGN4461 to REGN4461 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 9 Participants |
| SBTP Arm 1 Cohort A: Placebo to REGN4461 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 3 Participants |
| SBTP Arm 2 Cohort A: REGN4461 to REGN4461 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 5 Participants |
| SBTP Arm 1 Cohort B: Placebo to REGN4461 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 3 Participants |
| SBTP Arm 2 Cohort B: REGN4461 to REGN4461 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 4 Participants |
| SBTP Arm 1 Combined Cohort A + B: Placebo to REGN4461 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 6 Participants |
| SBTP Arm 2 Combined Cohort A + B: REGN4461 to REGN4461 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 9 Participants |
Secondary
Number of Participants With Treatment-emergent Anti-drug Antibody (ADA) Response
Time frame: Up to Day 281
Population: The ADA analysis set included all treated participants who received any amount of study drug and had at least one non-missing anti-drug antibody result following the first dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1 Cohort A: Placebo to REGN4461 | Number of Participants With Treatment-emergent Anti-drug Antibody (ADA) Response | 0 Participants |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Number of Participants With Treatment-emergent Anti-drug Antibody (ADA) Response | 0 Participants |
Secondary
Percent Change From Baseline to Week 12 in Fasting Serum TG (Cohorts B and A + B)
Percent change in fasting serum TG was reported for participants with elevated baseline fasting TG (\>200 mg/dL) in Cohort B and Cohorts A + B.
Time frame: Baseline to week 12
Population: The FAS included all randomized participants who received any study drug in the DBTP and had at least 1 post-baseline assessment. Here, Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 Cohort A: Placebo to REGN4461 | Percent Change From Baseline to Week 12 in Fasting Serum TG (Cohorts B and A + B) | 36.78 percent change | Standard Deviation 44.863 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Percent Change From Baseline to Week 12 in Fasting Serum TG (Cohorts B and A + B) | -35.59 percent change | Standard Deviation 8.754 |
| Arm 1 Combined Cohort A + B: Placebo to REGN4461 | Percent Change From Baseline to Week 12 in Fasting Serum TG (Cohorts B and A + B) | 10.07 percent change | Standard Deviation 49.689 |
| Arm 2 Combined Cohort A + B: REGN4461 to REGN4461 | Percent Change From Baseline to Week 12 in Fasting Serum TG (Cohorts B and A + B) | -37.62 percent change | Standard Deviation 13.752 |
Secondary
Percent Change From Baseline to Weeks 12 and 24 in Fasting Serum TG (Study Arm 1)
Percent change in fasting serum TG was reported for participants in Study Arm 1.
Time frame: Baseline, Week 12, Week 24
Population: The FAS included all randomized participants who received any study drug in the DBTP and had at least 1 post-baseline assessment. Here, Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure, and Number analyzed is the number of participants evaluated at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 Cohort A: Placebo to REGN4461 | Percent Change From Baseline to Weeks 12 and 24 in Fasting Serum TG (Study Arm 1) | Week 12 | -11.30 percent change | Standard Deviation 46.306 |
| Arm 1 Cohort A: Placebo to REGN4461 | Percent Change From Baseline to Weeks 12 and 24 in Fasting Serum TG (Study Arm 1) | Week 24 | -29.79 percent change | Standard Deviation 35.109 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Percent Change From Baseline to Weeks 12 and 24 in Fasting Serum TG (Study Arm 1) | Week 12 | 36.78 percent change | Standard Deviation 44.863 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Percent Change From Baseline to Weeks 12 and 24 in Fasting Serum TG (Study Arm 1) | Week 24 | -8.96 percent change | Standard Deviation 13.673 |
| Arm 1 Combined Cohort A + B: Placebo to REGN4461 | Percent Change From Baseline to Weeks 12 and 24 in Fasting Serum TG (Study Arm 1) | Week 12 | 10.07 percent change | Standard Deviation 49.689 |
| Arm 1 Combined Cohort A + B: Placebo to REGN4461 | Percent Change From Baseline to Weeks 12 and 24 in Fasting Serum TG (Study Arm 1) | Week 24 | -23.84 percent change | Standard Deviation 30.923 |
Secondary
Percent Change From Baseline to Weeks 12 and 24 in Fasting Serum TG (Study Arm 2)
Percent change in fasting serum TG was reported for participants in Study Arm 2.
Time frame: Baseline, Week 12, Week 24
Population: The FAS included all randomized participants who received any study drug in the DBTP and had at least 1 post-baseline assessment. Here, Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure, and Number analyzed is the number of participants evaluated at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 Cohort A: Placebo to REGN4461 | Percent Change From Baseline to Weeks 12 and 24 in Fasting Serum TG (Study Arm 2) | Week 12 | -38.97 percent change | Standard Deviation 16.998 |
| Arm 1 Cohort A: Placebo to REGN4461 | Percent Change From Baseline to Weeks 12 and 24 in Fasting Serum TG (Study Arm 2) | Week 24 | -30.77 percent change | Standard Deviation 48.883 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Percent Change From Baseline to Weeks 12 and 24 in Fasting Serum TG (Study Arm 2) | Week 12 | -35.59 percent change | Standard Deviation 8.754 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Percent Change From Baseline to Weeks 12 and 24 in Fasting Serum TG (Study Arm 2) | Week 24 | -5.30 percent change | Standard Deviation 51.158 |
| Arm 1 Combined Cohort A + B: Placebo to REGN4461 | Percent Change From Baseline to Weeks 12 and 24 in Fasting Serum TG (Study Arm 2) | Week 12 | -37.62 percent change | Standard Deviation 13.752 |
| Arm 1 Combined Cohort A + B: Placebo to REGN4461 | Percent Change From Baseline to Weeks 12 and 24 in Fasting Serum TG (Study Arm 2) | Week 24 | -18.04 percent change | Standard Deviation 48.282 |
Secondary
Percent Change From Baseline to Weeks 12 and 24 in Liver Fat Magnetic Resonance Imaging-derived Proton Density Fat Fraction (MRI-PDFF) (Study Arm 1)
Percent change from baseline in MRI-PDFF was reported for participants with baseline MRI-PDFF ≥8.5% in Study Arm 1.
Time frame: Baseline, Week 12, Week 24
Population: The FAS included all randomized participants who received any study drug in the DBTP and had at least 1 post-baseline assessment. Here, Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure with baseline MRI-PDFF ≥8.5%, and Number analyzed is the number of participants evaluated at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 Cohort A: Placebo to REGN4461 | Percent Change From Baseline to Weeks 12 and 24 in Liver Fat Magnetic Resonance Imaging-derived Proton Density Fat Fraction (MRI-PDFF) (Study Arm 1) | Week 12 | -11.44 percent change | Standard Deviation 18.576 |
| Arm 1 Cohort A: Placebo to REGN4461 | Percent Change From Baseline to Weeks 12 and 24 in Liver Fat Magnetic Resonance Imaging-derived Proton Density Fat Fraction (MRI-PDFF) (Study Arm 1) | Week 24 | -47.21 percent change | Standard Deviation 22.176 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Percent Change From Baseline to Weeks 12 and 24 in Liver Fat Magnetic Resonance Imaging-derived Proton Density Fat Fraction (MRI-PDFF) (Study Arm 1) | Week 12 | -0.74 percent change | Standard Deviation 9.919 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Percent Change From Baseline to Weeks 12 and 24 in Liver Fat Magnetic Resonance Imaging-derived Proton Density Fat Fraction (MRI-PDFF) (Study Arm 1) | Week 24 | 44.81 percent change | — |
| Arm 1 Combined Cohort A + B: Placebo to REGN4461 | Percent Change From Baseline to Weeks 12 and 24 in Liver Fat Magnetic Resonance Imaging-derived Proton Density Fat Fraction (MRI-PDFF) (Study Arm 1) | Week 12 | -7.16 percent change | Standard Deviation 15.214 |
| Arm 1 Combined Cohort A + B: Placebo to REGN4461 | Percent Change From Baseline to Weeks 12 and 24 in Liver Fat Magnetic Resonance Imaging-derived Proton Density Fat Fraction (MRI-PDFF) (Study Arm 1) | Week 24 | -16.54 percent change | Standard Deviation 55.394 |
Secondary
Percent Change From Baseline to Weeks 12 and 24 in Liver Fat MRI-PDFF (Study Arm 2)
Percent change from baseline in MRI-PDFF was reported for participants with baseline liver fat MRI-PDFF ≥8.5% in Study Arm 2.
Time frame: Baseline, Week 12, Week 24
Population: The FAS included all randomized participants who received any study drug in the DBTP and had at least 1 post-baseline assessment. Here, Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure with baseline MRI-PDFF ≥8.5%, and Number analyzed is the number of participants evaluated at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 Cohort A: Placebo to REGN4461 | Percent Change From Baseline to Weeks 12 and 24 in Liver Fat MRI-PDFF (Study Arm 2) | Week 12 | -17.05 percent change | Standard Deviation 25.788 |
| Arm 1 Cohort A: Placebo to REGN4461 | Percent Change From Baseline to Weeks 12 and 24 in Liver Fat MRI-PDFF (Study Arm 2) | Week 24 | -24.33 percent change | Standard Deviation 27.151 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Percent Change From Baseline to Weeks 12 and 24 in Liver Fat MRI-PDFF (Study Arm 2) | Week 12 | -18.80 percent change | Standard Deviation 17.3 |
| Arm 2 Cohort A: REGN4461 to REGN4461 | Percent Change From Baseline to Weeks 12 and 24 in Liver Fat MRI-PDFF (Study Arm 2) | Week 24 | -19.53 percent change | Standard Deviation 19.324 |
| Arm 1 Combined Cohort A + B: Placebo to REGN4461 | Percent Change From Baseline to Weeks 12 and 24 in Liver Fat MRI-PDFF (Study Arm 2) | Week 24 | -22.27 percent change | Standard Deviation 22.353 |
| Arm 1 Combined Cohort A + B: Placebo to REGN4461 | Percent Change From Baseline to Weeks 12 and 24 in Liver Fat MRI-PDFF (Study Arm 2) | Week 12 | -17.92 percent change | Standard Deviation 20.351 |