CompletedNCT04183192Updated Apr 22, 2024Results posted

Pharmacodynamic Biomarkers to Support Biosimilar Development: Interleukin-5 Antagonists

A Phase 1 interventional study of Mepolizumab and Mepolizumab in Healthy Subjects, Pharmacokinetics and Pharmacodynamics, sponsored by Food and Drug Administration (FDA). Completed at 1 site in United States. Open to participants aged 18 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-04-22.

Sponsored by Food and Drug Administration (FDA) · Phase 1, Interventional, and Other

Phase: Phase 1
Study type: Interventional
Enrollment: 72
Allocation: Randomized
Ages: 18 Years to 55 Years
Sex: All

Study summary

This study is designed to assess pharmacokinetics and pharmacodynamics of mepolizumab and reslizumab across an appropriate dose range to inform clinical trial operating characteristics for future clinical pharmacology pharmacodynamics similarity studies.

Read the detailed description

This is a randomized, placebo-controlled, single-dose, parallel arm study in 72 healthy subjects assigned to one of four dose groups (low, intermediate low, intermediate high, and high) of each drug (mepolizumab or reslizumab) or placebo. Mepolizumab doses are 3, 6, 12, or 24 mg. Reslizumab doses are 0.1, 0.2, 0.4, or 0.8 mg/kg. Each arm will include 8 subjects (4 male and 4 female).

Subjects will be admitted for treatment on day -1 and receive a single dose of study drug or placebo on day 1. Depending on the treatment arm, subjects will remain in confinement for two weeks and continue follow-up through either day 63 or day 123.

Blood samples (approximately 5 mL per sample) will be collected for determination of plasma concentrations for study drug. Additional blood samples will be collected for determination of eosinophil counts (5 mL per sample; pharmacodynamic measure) and exploratory proteomics analyses (5 mL per sample).

Safety evaluations will include adverse event (AE) monitoring, vital sign measurements, and physical examinations. All AEs reported by the subject or observed by the investigator or clinical research unit (CRU) staff will be recorded. Any AE reported after the informed consent is signed and before study drug application will be recorded as medical history.

Conditions studied

Healthy Subjects
Pharmacokinetics
Pharmacodynamics

Keywords

Pharmacokinetics
Pharmacodynamics

In context

Lead sponsor

Food and Drug Administration (FDA) is the lead sponsor of 25 studies on the registry; 2 are open to participants now.

Of its 15 completed or terminated interventional studies of FDA-regulated products, 13 (87%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 55 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

Inclusion criteria

Subject signs an institutional review board approved written informed consent and privacy language as per national regulations (e.g., Health Insurance Portability and Accountability Act authorization) before any study related procedures are performed.
Subject is a healthy man or woman, 18 to 55 years of age, inclusive, who has a body mass index of 18.5 to 29.9 kg/m2, inclusive, at Screening.
Subject has normal medical history findings, clinical laboratory results, vital sign measurements, 12 lead electrocardiogram (ECG) results, and physical examination findings at screening or, if abnormal, the abnormality is not considered clinically significant (as determined and documented by the investigator or designee).
Subject must have a negative test result for alcohol and drugs of abuse at screening and Check-in (Day -1).
Subject has a peripheral blood eosinophil count of ≥50 and ≤700 cells per microliter of blood as measured by a standard hematology analyzer.
Female subjects must be of non-childbearing potential or, if they are of childbearing potential, they must: 1) have been strictly abstinent for 1 month before Check in (Day -1) and agree to remain strictly abstinent for the duration of the study and for at least 1month after the last application of study drug; OR 2) be practicing 2 highly effective methods of birth control (as determined by the investigator or designee; one of the methods must be a barrier technique) from at least 1 month before Check in (Day -1) until at least 1 month after the end of the study.
Male subjects must agree to practice 1 highly effective method of birth control (as determined by the investigator or designee) from at least 1 month before Check in (Day -1) until at least 1 month after the end of the study.
Subject is highly likely (as determined by the investigator) to comply with the protocol defined procedures and to complete the study

Exclusion criteria

Exclusion Criteria:

Subject is taking any medication known to affect leukocyte population numbers.
Subject is anemic (i.e., with Hct or Hgb less than the lower limit of normal) or has any chronic condition(s) that may impact blood sample collection.
Subject has had previous exposure to the biologic mepolizumab or reslizumab.
Subject has a history of asthma.
Subject has a history of anaphylaxis from environmental exposures such as peanuts or bee stings.
Subject has an allergic history that includes urticaria, angioedema or respiratory coughing or bronchospasm.
Subject has a history of severe local reactions or generalized erythema from skin allergen testing.
Subject is anemic or has any chronic condition(s) that may impact blood sample collection.
Subject has used any prescription or nonprescription drugs (including aspirin or NSAIDs and excluding oral contraceptives and acetaminophen) within 14 days or 5 half-lives (whichever is longer) or complementary and alternative medicines within 28 days before the first dose of study drug.
Subjects are currently participating in another clinical study of an investigational drug or are have been treated with any investigational drug within 30 days or 5 half-lives (whichever is longer) of the compound.
Subject has used nicotine-containing products (e.g., cigarettes, cigars, chewing tobacco, snuff) within 6 weeks of Screening.
Subject has consumed alcohol, xanthine containing products (e.g., tea, coffee, chocolate, cola), caffeine, grapefruit, or grapefruit juice within 48 hours of dosing. Subjects must refrain from ingesting these throughout the study.
Subject has any underlying disease or surgical or medical condition (e.g., cancer, human immunodeficiency virus [HIV], severe hepatic or renal impairment) that could put the subject at risk or would normally prevent participation in a clinical study. This includes subjects with any underlying medical conditions that put subjects at higher risk for coronavirus disease of 2019 (COVID-19) complications; per current Center for Disease Control and Prevention (CDC) recommendations this includes:
- People with chronic lung disease or moderate to severe asthma
- People who have serious heart conditions
- People who are immunocompromised
- Many conditions can cause a person to be immunocompromised, including cancer treatment, smoking, bone marrow or organ transplantation, immune deficiencies, poorly controlled HIV, and prolonged use of corticosteroids and other immune weakening medications
- People with severe obesity (body mass index [BMI] of 40 or higher)
- People with diabetes
- People with chronic kidney disease undergoing dialysis
- People with liver disease
Subject has any signs or symptoms that are consistent with COVID-19. Per current CDC recommendations this includes subjects with the symptoms cough or shortness of breath or difficulty breathing, or at least two of the following symptoms: fever, chills, repeated shaking with chills, muscle pain, headache, sore throat or new loss of taste/smell. In addition, the subject has any other findings suggestive of COVID-19 risk in the opinion of the investigator.
Subject tests positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by a molecular diagnostic test performed prior to admission.
Subject has known or suspected allergies or sensitivities to any study drug.
Subject has clinical laboratory test results (hematology, serum chemistry) at Screening that are outside the reference ranges provided by the clinical laboratory and considered clinically significant by the investigator.
Subject has a positive test result at Screening for HIV 1 or 2 antibody, hepatitis C virus antibodies, or hepatitis B surface antigen.
Subject is unable or unwilling to undergo multiple venipunctures for blood sample collection because of poor tolerability or poor venous access.
Female subjects are pregnant or lactating before enrollment in the study.
Subject is known to have, or is suspected to have, a parasitic infection.

Study design

Phase: Phase 1
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Double (Participant, Investigator)
Enrollment: 72 participants (actual)

Study arms

Experimental
Arm A: Mepolizumab low dose
Single dose of mepolizumab 3 mg SC
Biological: Mepolizumab
Experimental
Arm B: Mepolizumab low intermediate dose
Single dose of mepolizumab 6 mg SC
Biological: Mepolizumab
Experimental
Arm C: Mepolizumab high intermediate dose
Single dose of mepolizumab 12 mg SC
Biological: Mepolizumab
Experimental
Arm D: Mepolizumab high dose
Single dose of mepolizumab 24 mg SC
Biological: Mepolizumab
Experimental
Arm E: Reslizumab low dose
Single dose of reslizumab 0.1 mg/kg IV
Biological: Reslizumab
Experimental
Arm F: Reslizumab intermediate low dose
Single dose of reslizumab 0.2 mg/kg IV
Biological: Reslizumab
Experimental
Arm G: Reslizumab high intermediate dose
Single dose of reslizumab 0.4 mg/kg IV
Biological: Reslizumab
Experimental
Arm H: Reslizumab high dose
Single dose of reslizumab 0.8 mg/kg IV
Biological: Reslizumab
Placebo comparator
Arm I: Placebo
Single dose of placebo
Biological: Placebo

Interventions

BiologicalMepolizumab
Mepolizumab 3 mg administered SC
BiologicalMepolizumab
Mepolizumab 6 mg administered SC
BiologicalMepolizumab
Mepolizumab 12 mg administered SC
BiologicalMepolizumab
Mepolizumab 24 mg administered SC
BiologicalReslizumab
Reslizumab 0.1 mg/kg administered IV
BiologicalReslizumab
Reslizumab 0.2 mg/kg administered IV
BiologicalReslizumab
Reslizumab 0.4 mg/kg administered IV
BiologicalReslizumab
Reslizumab 0.8 mg/kg administered IV
BiologicalPlacebo
Placebo (administered either IV or SC)

What researchers measure

Primary outcomes

Area Under Effect Curve (AUEC) for Eosinophils for Mepolizumab and Reslizumab
The values and variability of AUEC for eosinophils at low, intermediate low, intermediate high, and high doses of mepolizumab and reslizumab. AUEC was calculated as percentage change from baseline and used all measures from time zero to the last sample collected on study. Calculations were performed using non-compartmental analysis packages available in R software.
Time frame: Day -1 and 0h (pre-dose), 24h (post-dose); once daily from Day 2 onwards until Day 14 post-dose; once weekly from Day 21 onwards until Day 63 post-dose for Arms A, B, E, F and until Day 123 post-dose for Arms C, D, G, H, and I.
Maximum Change From Baseline for Eosinophils for Mepolizumab and Reslizumab
The values and variability of maximal change from baseline for eosinophils at low, intermediate low, intermediate high, and high doses of mepolizumab and reslizumab. Values are percentage change from baseline.
Time frame: Day -1 and 0h (pre-dose), 24h (post-dose); once daily from Day 2 onwards until Day 14 post-dose; once weekly from Day 21 onwards until Day 63 post-dose for Arms A, B, E, F and until Day 123 post-dose for Arms C, D, G, H, and I.

Secondary outcomes

Maximum Concentration (Cmax) for Mepolizumab and Reslizumab
The values and variability of Cmax at low, intermediate low, intermediate high, and high doses of mepolizumab and reslizumab.
Time frame: 0 (pre-dose), 1, 4, 12, 24, hours post-dose; once daily from Day 3 onwards until Day 14 post-dose; once weekly from Day 21 onwards until Day 63 post-dose for Arms A, B, E, F and until Day 123 post-dose for Arms C, D, G, and H.
Area Under the Curve (AUC) for Mepolizumab and Reslizumab
The values and variability of AUC at low, intermediate low, intermediate high, and high doses of mepolizumab and reslizumab.
Time frame: 0 (pre-dose), 1, 4, 12, 24, hours post-dose; once daily from Day 3 onwards until Day 14 post-dose; once weekly from Day 21 onwards until Day 63 post-dose for Arms A, B, E, F and until Day 123 post-dose for Arms C, D, G, and H.
Pharmacodynamic Model Parameters (Maximum Effect [Emax]) for Eosinophil Area Under the Effect Curve Versus Dose Emax Models for Mepolizumab or Reslizumab
The model parameter (Emax, units percentage change from baseline \* day) from an Emax model for eosinophil area under the effect curve versus dose were calculated after combining data from low, intermediate low, intermediate high, and high doses of mepolizumab or reslizumab with placebo data. AUEC (units of percentage change from baseline \* day) was calculated as percentage change from baseline and used all measures from time zero to the last sample collected on study. Model-analyses were conducted using the DoseFinding package available in R software. Confidence intervals for model parameters were generated using bootstrapping of the estimated model with 2500 repetitions.
Time frame: Day -1 and 0h (pre-dose), 24h (post-dose); once daily from Day 2 onwards until Day 14 post-dose; once weekly from Day 21 onwards until Day 63 post-dose for Arms A, B, E, F and until Day 123 post-dose for Arms C, D, G, H, and I.
Pharmacodynamic Model Parameter, ED50 (Half Maximal Effect Dose), for Eosinophil Area Under the Effect Curve Versus Dose Emax Model for Mepolizumab
The model parameter (ED50, units mg) from an Emax model for eosinophil area under the effect curve versus dose were calculated after combining data from low, intermediate low, intermediate high, and high doses of mepolizumab with placebo data. AUEC (units of percentage change from baseline \* day) was calculated as percentage change from baseline and used all measures from time zero to the last sample collected on study. Model-analyses were conducted using the DoseFinding package available in R software. Confidence intervals for model parameters were generated using bootstrapping of the estimated model with 2500 repetitions.
Time frame: Day -1 and 0h (pre-dose), 24h (post-dose); once daily from Day 2 onwards until Day 14 post-dose; once weekly from Day 21 onwards until Day 63 post-dose for Arms A, B, and until Day 123 post-dose for Arms C, D, and I.
Pharmacodynamic Model Parameter, ED50 (Half Maximal Effect Dose), for Eosinophil Area Under the Effect Curve Versus Dose Emax Model for Reslizumab
The model parameter (ED50, units mg/kg) from an Emax model for eosinophil area under the effect curve versus dose were calculated after combining data from low, intermediate low, intermediate high, and high doses of reslizumab with placebo data. AUEC (units of percentage change from baseline \* day) was calculated as percentage change from baseline and used all measures from time zero to the last sample collected on study. Model-analyses were conducted using the DoseFinding package available in R software. Confidence intervals for model parameters were generated using bootstrapping of the estimated model with 2500 repetitions.
Time frame: Day -1 and 0h (pre-dose), 24h (post-dose); once daily from Day 2 onwards until Day 14 post-dose; once weekly from Day 21 onwards until Day 63 post-dose for Arms E, F and until Day 123 post-dose for Arms G, H, and I.
Pharmacodynamic Model Parameters (Maximum Effect [Emax]) for Eosinophil Maximum Change From Baseline Versus Dose Emax Models With Mepolizumab or Reslizumab
The model parameter (Emax, units percentage change from baseline) from an Emax model for eosinophil maximum change from baseline versus dose was calculated after combining data from low, intermediate low, intermediate high, and high doses of mepolizumab or reslizumab with placebo data. Maximum change from baseline (units of percentage change from baseline) was calculated as percentage change from baseline and considered all measures from time zero to the last sample collected on study. Model-analyses were conducted using the DoseFinding package available in R software. Confidence intervals for model parameters were generated using bootstrapping of the estimated model with 2500 repetitions.
Time frame: Day -1 and 0h (pre-dose), 24h (post-dose); once daily from Day 2 onwards until Day 14 post-dose; once weekly from Day 21 onwards until Day 63 post-dose for Arms A, B, E, F and until Day 123 post-dose for Arms C, D, G, H, and I.
Pharmacodynamic Model Parameter, ED50 (Half Maximal Effect Dose), for Eosinophil Maximum Change From Baseline Curve Versus Dose Emax Model Mepolizumab
The model parameter (ED50, units mg) from an Emax model for eosinophil maximum change from baseline versus dose was calculated after combining data from low, intermediate low, intermediate high, and high doses of mepolizumab with placebo data. Maximum change from baseline (units of percentage change from baseline) was calculated as percentage change from baseline and considered all measures from time zero to the last sample collected on study. Model-analyses were conducted using the DoseFinding package available in R software. Confidence intervals for model parameters were generated using bootstrapping of the estimated model with 2500 repetitions.
Time frame: Day -1 and 0h (pre-dose), 24h (post-dose); once daily from Day 2 onwards until Day 14 post-dose; once weekly from Day 21 onwards until Day 63 post-dose for Arms A, B, and until Day 123 post-dose for Arms C, D, and I.
Pharmacodynamic Model Parameter, ED50 (Half Maximal Effect Dose), for Eosinophil Maximum Change From Baseline Curve Versus Dose Emax Model Reslizumab
The model parameter (ED50, units mg/kg) from an Emax model for eosinophil maximum change from baseline versus dose was calculated after combining data from low, intermediate low, intermediate high, and high doses of reslizumab with placebo data. Maximum change from baseline (units of percentage change from baseline) was calculated as percentage change from baseline and considered all measures from time zero to the last sample collected on study. Model-analyses were conducted using the DoseFinding package available in R software. Confidence intervals for model parameters were generated using bootstrapping of the estimated model with 2500 repetitions.
Time frame: Day -1 and 0h (pre-dose), 24h (post-dose); once daily from Day 2 onwards until Day 14 post-dose; once weekly from Day 21 onwards until Day 63 post-dose for Arms E, F and until Day 123 post-dose for Arms G, H, and I.

Results

Posted Apr 22, 2024

Participant flow

Participant flow — Overall Study
Milestone	Arm A: Mepolizumab Low Dose	Arm B: Mepolizumab Low Intermediate Dose	Arm C: Mepolizumab High Intermediate Dose	Arm D: Mepolizumab High Dose	Arm E: Reslizumab Low Dose	Arm F: Reslizumab Intermediate Low Dose	Arm G: Reslizumab High Intermediate Dose	Arm H: Reslizumab High Dose	Arm I: Placebo
Started	8	8	8	8	8	8	8	8	8
Completed	7	8	7	8	8	8	8	8	8
Not completed	1	0	1	0	0	0	0	0	0

Outcome measures

PrimaryArea Under Effect Curve (AUEC) for Eosinophils for Mepolizumab and Reslizumab

The values and variability of AUEC for eosinophils at low, intermediate low, intermediate high, and high doses of mepolizumab and reslizumab. AUEC was calculated as percentage change from baseline and used all measures from time zero to the last sample collected on study. Calculations were performed using non-compartmental analysis packages available in R software.

Time frame:: Day -1 and 0h (pre-dose), 24h (post-dose); once daily from Day 2 onwards until Day 14 post-dose; once weekly from Day 21 onwards until Day 63 post-dose for Arms A, B, E, F and until Day 123 post-dose for Arms C, D, G, H, and I.
Reported as:: Mean · Percentage change from baseline * day

Area Under Effect Curve (AUEC) for Eosinophils for Mepolizumab and Reslizumab
Percentage change from baseline * day	Arm A: Mepolizumab Low Dose	Arm B: Mepolizumab Low Intermediate Dose	Arm C: Mepolizumab High Intermediate Dose	Arm D: Mepolizumab High Dose	Arm E: Reslizumab Low Dose	Arm F: Reslizumab Intermediate Low Dose	Arm G: Reslizumab High Intermediate Dose	Arm H: Reslizumab High Dose	Arm I: Placebo
Area Under Effect Curve (AUEC) for Eosinophils for Mepolizumab and Reslizumab	-1804 ± 1425	-195 ± 1568	-1456 ± 1951	-1428 ± 2442	-1748 ± 1888	-1075 ± 1312	-3313 ± 4506	-2905 ± 1423	-1409 ± 3410

PrimaryMaximum Change From Baseline for Eosinophils for Mepolizumab and Reslizumab

The values and variability of maximal change from baseline for eosinophils at low, intermediate low, intermediate high, and high doses of mepolizumab and reslizumab. Values are percentage change from baseline.

Time frame:: Day -1 and 0h (pre-dose), 24h (post-dose); once daily from Day 2 onwards until Day 14 post-dose; once weekly from Day 21 onwards until Day 63 post-dose for Arms A, B, E, F and until Day 123 post-dose for Arms C, D, G, H, and I.
Reported as:: Mean · Percentage change from baseline

Maximum Change From Baseline for Eosinophils for Mepolizumab and Reslizumab
Percentage change from baseline	Arm A: Mepolizumab Low Dose	Arm B: Mepolizumab Low Intermediate Dose	Arm C: Mepolizumab High Intermediate Dose	Arm D: Mepolizumab High Dose	Arm E: Reslizumab Low Dose	Arm F: Reslizumab Intermediate Low Dose	Arm G: Reslizumab High Intermediate Dose	Arm H: Reslizumab High Dose	Arm I: Placebo
Maximum Change From Baseline for Eosinophils for Mepolizumab and Reslizumab	-72 ± 73	-63 ± 14	-82 ± 23	-85 ± 14	-79 ± 9	-67 ± 27	-75 ± 25	-77 ± 25	-41 ± 15

SecondaryMaximum Concentration (Cmax) for Mepolizumab and Reslizumab

The values and variability of Cmax at low, intermediate low, intermediate high, and high doses of mepolizumab and reslizumab.

Time frame:: 0 (pre-dose), 1, 4, 12, 24, hours post-dose; once daily from Day 3 onwards until Day 14 post-dose; once weekly from Day 21 onwards until Day 63 post-dose for Arms A, B, E, F and until Day 123 post-dose for Arms C, D, G, and H.
Reported as:: Geometric mean · μg/mL

Maximum Concentration (Cmax) for Mepolizumab and Reslizumab
μg/mL	Arm A: Mepolizumab Low Dose	Arm B: Mepolizumab Low Intermediate Dose	Arm C: Mepolizumab High Intermediate Dose	Arm D: Mepolizumab High Dose	Arm E: Reslizumab Low Dose	Arm F: Reslizumab Intermediate Low Dose	Arm G: Reslizumab High Intermediate Dose	Arm H: Reslizumab High Dose
Maximum Concentration (Cmax) for Mepolizumab and Reslizumab	0.36 ± 74	0.53 ± 54	1.21 ± 23	2.05 ± 27	3.1 ± 10	5.2 ± 35	12.3 ± 26	18.7 ± 20

SecondaryArea Under the Curve (AUC) for Mepolizumab and Reslizumab

The values and variability of AUC at low, intermediate low, intermediate high, and high doses of mepolizumab and reslizumab.

Time frame:: 0 (pre-dose), 1, 4, 12, 24, hours post-dose; once daily from Day 3 onwards until Day 14 post-dose; once weekly from Day 21 onwards until Day 63 post-dose for Arms A, B, E, F and until Day 123 post-dose for Arms C, D, G, and H.
Reported as:: Geometric mean · μg/mL*day

Area Under the Curve (AUC) for Mepolizumab and Reslizumab
μg/mL*day	Arm A: Mepolizumab Low Dose	Arm B: Mepolizumab Low Intermediate Dose	Arm C: Mepolizumab High Intermediate Dose	Arm D: Mepolizumab High Dose	Arm E: Reslizumab Low Dose	Arm F: Reslizumab Intermediate Low Dose	Arm G: Reslizumab High Intermediate Dose	Arm H: Reslizumab High Dose
Area Under the Curve (AUC) for Mepolizumab and Reslizumab	17.6 ± 73	21.7 ± 153	38.1 ± 21	61.8 ± 46	150 ± 109	152 ± 239	450 ± 72	420 ± 70

SecondaryPharmacodynamic Model Parameters (Maximum Effect [Emax]) for Eosinophil Area Under the Effect Curve Versus Dose Emax Models for Mepolizumab or Reslizumab

The model parameter (Emax, units percentage change from baseline \* day) from an Emax model for eosinophil area under the effect curve versus dose were calculated after combining data from low, intermediate low, intermediate high, and high doses of mepolizumab or reslizumab with placebo data. AUEC (units of percentage change from baseline \* day) was calculated as percentage change from baseline and used all measures from time zero to the last sample collected on study. Model-analyses were conducted using the DoseFinding package available in R software. Confidence intervals for model parameters were generated using bootstrapping of the estimated model with 2500 repetitions.

Time frame:: Day -1 and 0h (pre-dose), 24h (post-dose); once daily from Day 2 onwards until Day 14 post-dose; once weekly from Day 21 onwards until Day 63 post-dose for Arms A, B, E, F and until Day 123 post-dose for Arms C, D, G, H, and I.
Reported as:: Mean · Percentage change from baseline * day

Pharmacodynamic Model Parameters (Maximum Effect [Emax]) for Eosinophil Area Under the Effect Curve Versus Dose Emax Models for Mepolizumab or Reslizumab
Percentage change from baseline * day	Mepolizumab: Area Under the Effect Curve Model for Eosinophils	Reslizumab: Area Under the Effect Curve Model for Eosinophils
Pharmacodynamic Model Parameters (Maximum Effect [Emax]) for Eosinophil Area Under the Effect Curve Versus Dose Emax Models for Mepolizumab or Reslizumab	10840 (6571 to 31670)	10446 (4138 to 22373)

SecondaryPharmacodynamic Model Parameter, ED50 (Half Maximal Effect Dose), for Eosinophil Area Under the Effect Curve Versus Dose Emax Model for Mepolizumab

The model parameter (ED50, units mg) from an Emax model for eosinophil area under the effect curve versus dose were calculated after combining data from low, intermediate low, intermediate high, and high doses of mepolizumab with placebo data. AUEC (units of percentage change from baseline \* day) was calculated as percentage change from baseline and used all measures from time zero to the last sample collected on study. Model-analyses were conducted using the DoseFinding package available in R software. Confidence intervals for model parameters were generated using bootstrapping of the estimated model with 2500 repetitions.

Time frame:: Day -1 and 0h (pre-dose), 24h (post-dose); once daily from Day 2 onwards until Day 14 post-dose; once weekly from Day 21 onwards until Day 63 post-dose for Arms A, B, and until Day 123 post-dose for Arms C, D, and I.
Reported as:: Mean · mg

Pharmacodynamic Model Parameter, ED50 (Half Maximal Effect Dose), for Eosinophil Area Under the Effect Curve Versus Dose Emax Model for Mepolizumab
mg	Mepolizumab: Area Under the Effect Curve Model for Eosinophils
Pharmacodynamic Model Parameter, ED50 (Half Maximal Effect Dose), for Eosinophil Area Under the Effect Curve Versus Dose Emax Model for Mepolizumab	31.3 (8.6 to 400)

SecondaryPharmacodynamic Model Parameter, ED50 (Half Maximal Effect Dose), for Eosinophil Area Under the Effect Curve Versus Dose Emax Model for Reslizumab

The model parameter (ED50, units mg/kg) from an Emax model for eosinophil area under the effect curve versus dose were calculated after combining data from low, intermediate low, intermediate high, and high doses of reslizumab with placebo data. AUEC (units of percentage change from baseline \* day) was calculated as percentage change from baseline and used all measures from time zero to the last sample collected on study. Model-analyses were conducted using the DoseFinding package available in R software. Confidence intervals for model parameters were generated using bootstrapping of the estimated model with 2500 repetitions.

Time frame:: Day -1 and 0h (pre-dose), 24h (post-dose); once daily from Day 2 onwards until Day 14 post-dose; once weekly from Day 21 onwards until Day 63 post-dose for Arms E, F and until Day 123 post-dose for Arms G, H, and I.
Reported as:: Mean · mg/kg

Pharmacodynamic Model Parameter, ED50 (Half Maximal Effect Dose), for Eosinophil Area Under the Effect Curve Versus Dose Emax Model for Reslizumab
mg/kg	Reslizumab: Area Under the Effect Curve Model for Eosinophils
Pharmacodynamic Model Parameter, ED50 (Half Maximal Effect Dose), for Eosinophil Area Under the Effect Curve Versus Dose Emax Model for Reslizumab	0.31 (0.01 to 1.20)

SecondaryPharmacodynamic Model Parameters (Maximum Effect [Emax]) for Eosinophil Maximum Change From Baseline Versus Dose Emax Models With Mepolizumab or Reslizumab

The model parameter (Emax, units percentage change from baseline) from an Emax model for eosinophil maximum change from baseline versus dose was calculated after combining data from low, intermediate low, intermediate high, and high doses of mepolizumab or reslizumab with placebo data. Maximum change from baseline (units of percentage change from baseline) was calculated as percentage change from baseline and considered all measures from time zero to the last sample collected on study. Model-analyses were conducted using the DoseFinding package available in R software. Confidence intervals for model parameters were generated using bootstrapping of the estimated model with 2500 repetitions.

Time frame:: Day -1 and 0h (pre-dose), 24h (post-dose); once daily from Day 2 onwards until Day 14 post-dose; once weekly from Day 21 onwards until Day 63 post-dose for Arms A, B, E, F and until Day 123 post-dose for Arms C, D, G, H, and I.
Reported as:: Mean · Percentage change from baseline

Pharmacodynamic Model Parameters (Maximum Effect [Emax]) for Eosinophil Maximum Change From Baseline Versus Dose Emax Models With Mepolizumab or Reslizumab
Percentage change from baseline	Mepolizumab: Maximum Change From Baseline Model for Eosinophils	Reslizumab: Maximum Change From Baseline Model for Eosinophils
Pharmacodynamic Model Parameters (Maximum Effect [Emax]) for Eosinophil Maximum Change From Baseline Versus Dose Emax Models With Mepolizumab or Reslizumab	85 (78 to 92)	86 (77 to 95)

SecondaryPharmacodynamic Model Parameter, ED50 (Half Maximal Effect Dose), for Eosinophil Maximum Change From Baseline Curve Versus Dose Emax Model Mepolizumab

The model parameter (ED50, units mg) from an Emax model for eosinophil maximum change from baseline versus dose was calculated after combining data from low, intermediate low, intermediate high, and high doses of mepolizumab with placebo data. Maximum change from baseline (units of percentage change from baseline) was calculated as percentage change from baseline and considered all measures from time zero to the last sample collected on study. Model-analyses were conducted using the DoseFinding package available in R software. Confidence intervals for model parameters were generated using bootstrapping of the estimated model with 2500 repetitions.

Time frame:: Day -1 and 0h (pre-dose), 24h (post-dose); once daily from Day 2 onwards until Day 14 post-dose; once weekly from Day 21 onwards until Day 63 post-dose for Arms A, B, and until Day 123 post-dose for Arms C, D, and I.
Reported as:: Mean · mg

Pharmacodynamic Model Parameter, ED50 (Half Maximal Effect Dose), for Eosinophil Maximum Change From Baseline Curve Versus Dose Emax Model Mepolizumab
mg	Mepolizumab: Maximum Change From Baseline Model for Eosinophils
Pharmacodynamic Model Parameter, ED50 (Half Maximal Effect Dose), for Eosinophil Maximum Change From Baseline Curve Versus Dose Emax Model Mepolizumab	3.8 (2.0 to 6.4)

SecondaryPharmacodynamic Model Parameter, ED50 (Half Maximal Effect Dose), for Eosinophil Maximum Change From Baseline Curve Versus Dose Emax Model Reslizumab

The model parameter (ED50, units mg/kg) from an Emax model for eosinophil maximum change from baseline versus dose was calculated after combining data from low, intermediate low, intermediate high, and high doses of reslizumab with placebo data. Maximum change from baseline (units of percentage change from baseline) was calculated as percentage change from baseline and considered all measures from time zero to the last sample collected on study. Model-analyses were conducted using the DoseFinding package available in R software. Confidence intervals for model parameters were generated using bootstrapping of the estimated model with 2500 repetitions.

Time frame:: Day -1 and 0h (pre-dose), 24h (post-dose); once daily from Day 2 onwards until Day 14 post-dose; once weekly from Day 21 onwards until Day 63 post-dose for Arms E, F and until Day 123 post-dose for Arms G, H, and I.
Reported as:: Mean · mg/kg

Pharmacodynamic Model Parameter, ED50 (Half Maximal Effect Dose), for Eosinophil Maximum Change From Baseline Curve Versus Dose Emax Model Reslizumab
mg/kg	Reslizumab: Maximum Change From Baseline Model for Eosinophils
Pharmacodynamic Model Parameter, ED50 (Half Maximal Effect Dose), for Eosinophil Maximum Change From Baseline Curve Versus Dose Emax Model Reslizumab	0.04 (0.01 to 0.08)

Adverse events

Collected over 63 days for subjects in treatment groups A,B,E,F and 123 days for subjects in treatment groups C,D,G, H.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Arm A: Mepolizumab Low Dose	0/8 (0%)	0/8 (0%)	4/8 (50%)
Arm B: Mepolizumab Low Intermediate Dose	0/8 (0%)	0/8 (0%)	3/8 (37.5%)
Arm C: Mepolizumab High Intermediate Dose	0/8 (0%)	0/8 (0%)	3/8 (37.5%)
Arm D: Mepolizumab High Dose	0/8 (0%)	0/8 (0%)	1/8 (12.5%)
Arm E: Reslizumab Low Dose	0/8 (0%)	0/8 (0%)	3/8 (37.5%)
Arm F: Reslizumab Intermediate Low Dose	0/8 (0%)	0/8 (0%)	2/8 (25%)
Arm G: Reslizumab High Intermediate Dose	0/8 (0%)	0/8 (0%)	4/8 (50%)
Arm H: Reslizumab High Dose	0/8 (0%)	0/8 (0%)	6/8 (75%)
Arm I: Placebo	0/8 (0%)	0/8 (0%)	3/8 (37.5%)

Most frequent other events

Showing 10 of 33

Most frequent other events
Event	Arm A: Mepolizumab Low Dose	Arm B: Mepolizumab Low Intermediate Dose	Arm C: Mepolizumab High Intermediate Dose	Arm D: Mepolizumab High Dose	Arm E: Reslizumab Low Dose	Arm F: Reslizumab Intermediate Low Dose	Arm G: Reslizumab High Intermediate Dose	Arm H: Reslizumab High Dose	Arm I: Placebo
NauseaGastrointestinal disorders	1/8	0/8	1/8	0/8	0/8	0/8	2/8	0/8	1/8
Vessel puncture site painGeneral disorders	0/8	1/8	0/8	0/8	2/8	0/8	0/8	1/8	0/8
Eye irritationEye disorders	0/8	0/8	1/8	0/8	0/8	0/8	0/8	0/8	0/8
PhotophobiaEye disorders	0/8	0/8	0/8	0/8	0/8	0/8	1/8	0/8	0/8
Abdominal painGastrointestinal disorders	1/8	1/8	0/8	0/8	0/8	0/8	0/8	0/8	0/8
DiarrhoeaGastrointestinal disorders	1/8	0/8	0/8	0/8	0/8	0/8	0/8	0/8	0/8
DyspepsiaGastrointestinal disorders	1/8	0/8	1/8	0/8	0/8	0/8	0/8	1/8	0/8
FlatulenceGastrointestinal disorders	0/8	0/8	1/8	0/8	0/8	0/8	0/8	0/8	0/8
VomitingGastrointestinal disorders	1/8	0/8	0/8	0/8	0/8	0/8	0/8	0/8	0/8
FatigueGeneral disorders	0/8	0/8	1/8	0/8	0/8	0/8	0/8	0/8	0/8

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Arm A: Mepolizumab Low Dose	Arm B: Mepolizumab Low Intermediate Dose	Arm C: Mepolizumab High Intermediate Dose	Arm D: Mepolizumab High Dose	Arm E: Reslizumab Low Dose	Arm F: Reslizumab Intermediate Low Dose	Arm G: Reslizumab High Intermediate Dose	Arm H: Reslizumab High Dose	Arm I: Placebo	Total
Median	32 (25 to 50)	29 (23 to 45)	33 (28 to 50)	39 (34 to 42)	46 (35 to 52)	36 (31 to 41)	45 (28 to 50)	49 (33 to 51)	40 (30 to 52)	39 (28 to 50)

Sex: Female, Male
Sex: Female, Male(Participants)	Arm A: Mepolizumab Low Dose	Arm B: Mepolizumab Low Intermediate Dose	Arm C: Mepolizumab High Intermediate Dose	Arm D: Mepolizumab High Dose	Arm E: Reslizumab Low Dose	Arm F: Reslizumab Intermediate Low Dose	Arm G: Reslizumab High Intermediate Dose	Arm H: Reslizumab High Dose	Arm I: Placebo	Total
Female	3	2	3	3	2	2	2	2	2	21
Male	5	6	5	5	6	6	6	6	6	51

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Arm A: Mepolizumab Low Dose	Arm B: Mepolizumab Low Intermediate Dose	Arm C: Mepolizumab High Intermediate Dose	Arm D: Mepolizumab High Dose	Arm E: Reslizumab Low Dose	Arm F: Reslizumab Intermediate Low Dose	Arm G: Reslizumab High Intermediate Dose	Arm H: Reslizumab High Dose	Arm I: Placebo	Total
Hispanic or Latino	2	0	1	1	0	2	1	1	1	9
Not Hispanic or Latino	6	8	7	7	8	6	7	7	7	63
Unknown or Not Reported	0	0	0	0	0	0	0	0	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Arm A: Mepolizumab Low Dose	Arm B: Mepolizumab Low Intermediate Dose	Arm C: Mepolizumab High Intermediate Dose	Arm D: Mepolizumab High Dose	Arm E: Reslizumab Low Dose	Arm F: Reslizumab Intermediate Low Dose	Arm G: Reslizumab High Intermediate Dose	Arm H: Reslizumab High Dose	Arm I: Placebo	Total
American Indian or Alaska Native	0	0	0	0	0	2	0	0	0	2
Asian	0	1	0	0	0	1	0	0	0	2
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0	0	0	0
Black or African American	5	2	6	4	5	3	3	2	3	33
White	3	5	2	4	3	2	3	6	5	33
More than one race	0	0	0	0	0	0	2	0	0	2
Unknown or Not Reported	0	0	0	0	0	0	0	0	0	0

Region of Enrollment
Region of Enrollment(participants)	Arm A: Mepolizumab Low Dose	Arm B: Mepolizumab Low Intermediate Dose	Arm C: Mepolizumab High Intermediate Dose	Arm D: Mepolizumab High Dose	Arm E: Reslizumab Low Dose	Arm F: Reslizumab Intermediate Low Dose	Arm G: Reslizumab High Intermediate Dose	Arm H: Reslizumab High Dose	Arm I: Placebo	Total
United States	8	8	8	8	8	8	8	8	8	72

Body Weight
Body Weight(kg)	Arm A: Mepolizumab Low Dose	Arm B: Mepolizumab Low Intermediate Dose	Arm C: Mepolizumab High Intermediate Dose	Arm D: Mepolizumab High Dose	Arm E: Reslizumab Low Dose	Arm F: Reslizumab Intermediate Low Dose	Arm G: Reslizumab High Intermediate Dose	Arm H: Reslizumab High Dose	Arm I: Placebo	Total
Median	73 (68 to 81)	71 (67 to 82)	72 (68 to 81)	79 (66 to 84)	75 (67 to 85)	80 (75 to 84)	78 (73 to 87)	72 (67 to 80)	82 (73 to 84)	77 (68 to 84)

Body Mass Index
Body Mass Index(kg/m^2)	Arm A: Mepolizumab Low Dose	Arm B: Mepolizumab Low Intermediate Dose	Arm C: Mepolizumab High Intermediate Dose	Arm D: Mepolizumab High Dose	Arm E: Reslizumab Low Dose	Arm F: Reslizumab Intermediate Low Dose	Arm G: Reslizumab High Intermediate Dose	Arm H: Reslizumab High Dose	Arm I: Placebo	Total
Median	25.3 (23.6 to 27.8)	23.7 (22.9 to 27.4)	26.7 (24.6 to 28.4)	24.8 (24.0 to 26.3)	23.9 (22.4 to 26.6)	27.5 (24.2 to 28.9)	26.2 (24.5 to 28.2)	23.8 (22.1 to 26.9)	27.5 (24.4 to 29.1)	25.6 (23.0 to 28.1)

Study locations

1 site

Spaulding Clinical Research
West Bend, Wisconsin 53095, United States

References and documents

Study documents

Study protocol · Jun 25, 2020
Statistical analysis plan · Jul 23, 2021
Informed consent form · Jun 25, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Plan is to make data from the study publicly available as a part of manuscript publication. In addition, the protocol and statistical analysis plan will be made available online at this site as well as any eventual publications.

Supporting information: Study protocol, Sap

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Apr 22, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT04183192
Lead sponsor: Food and Drug Administration (FDA)
Collaborators: Spaulding Clinical Research LLC
Responsible party: Sponsor
First posted: Dec 3, 2019
Start date: Feb 17, 2020
Primary completion: Apr 4, 2021
Completion: Apr 4, 2021
Results posted: Apr 22, 2024
Last update: Apr 22, 2024

Study contacts

Jennifer Deering, MSN, APNP

principal investigator · Spaulding Clinical Research LLC

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Nov 2023. You cannot join it, but the record below documents what was studied.

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