Healthy SubjectsPhase 1NCT04183192
Pharmacodynamic Biomarkers to Support Biosimilar Development: Interleukin-5 Antagonists
A Phase 1 study testing Mepolizumab and Reslizumab in people with Healthy Subjects and Pharmacokinetics, run by Food and Drug Administration (FDA) at 1 site in United States.
Trial 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 more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Subjects, Pharmacokinetics, Pharmacodynamics
- What is being tested?
- Mepolizumab and Reslizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 72 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Feb 2020to 4 Apr 2021
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 29Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Spaulding Clinical Research
West Bend, Wisconsin, 53095
About this study
Official title: Pharmacodynamic Biomarkers to Support Biosimilar Development: Clinical Study 1: Interleukin-5 Antagonists - Mepolizumab and Reslizumab
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.
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.
Read the detailed description
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.
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
- Healthy Subjects, Pharmacokinetics, Pharmacodynamics
- Being tested
- Mepolizumab, Reslizumab, Placebo
- Keywords
- Pharmacokinetics, Pharmacodynamics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MepolizumabBiological
Mepolizumab 3 mg administered SC
MepolizumabBiological
Mepolizumab 6 mg administered SC
MepolizumabBiological
Mepolizumab 12 mg administered SC
MepolizumabBiological
Mepolizumab 24 mg administered SC
ReslizumabBiological
Reslizumab 0.1 mg/kg administered IV
ReslizumabBiological
Reslizumab 0.2 mg/kg administered IV
ReslizumabBiological
Reslizumab 0.4 mg/kg administered IV
ReslizumabBiological
Reslizumab 0.8 mg/kg administered IV
PlaceboBiological
Placebo (administered either IV or SC)
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Mepolizumab low dose | Experimental | Single dose of mepolizumab 3 mg SC Receives: Biological: Mepolizumab |
| Arm B: Mepolizumab low intermediate dose | Experimental | Single dose of mepolizumab 6 mg SC Receives: Biological: Mepolizumab |
| Arm C: Mepolizumab high intermediate dose | Experimental | Single dose of mepolizumab 12 mg SC Receives: Biological: Mepolizumab |
| Arm D: Mepolizumab high dose | Experimental | Single dose of mepolizumab 24 mg SC Receives: Biological: Mepolizumab |
| Arm E: Reslizumab low dose | Experimental | Single dose of reslizumab 0.1 mg/kg IV Receives: Biological: Reslizumab |
| Arm F: Reslizumab intermediate low dose | Experimental | Single dose of reslizumab 0.2 mg/kg IV Receives: Biological: Reslizumab |
| Arm G: Reslizumab high intermediate dose | Experimental | Single dose of reslizumab 0.4 mg/kg IV Receives: Biological: Reslizumab |
| Arm H: Reslizumab high dose | Experimental | Single dose of reslizumab 0.8 mg/kg IV Receives: Biological: Reslizumab |
| Arm I: Placebo | Placebo comparator | Single dose of placebo Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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 (8)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2019
- Study start17 Feb 2020
- Primary completion4 Apr 2021
- Study completion4 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Healthy SubjectsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Subjects will be randomized to one of four dose groups (low, intermediate low, intermediate high, and high) of each drug (mepolizumab or reslizumab) or placebo
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- Food and Drug Administration (FDA)
- Sponsor type
- US federal agency
- Collaborators
- Spaulding Clinical Research LLC
- Responsible party
- Sponsor
- Investigators
- Jennifer Deering, MSN, APNP, Principal investigator, Spaulding Clinical Research LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04183192
- Sponsor's protocol ID
- SCR-006
- Status last verified
- Nov 2023
- First submitted
- 27 Nov 2019
- Last updated
- 22 Apr 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- 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.
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacodynamic Biomarkers to Support Biosimilar Development: Clinical Study 1: Interleukin-5 Antagonists - Mepolizumab and Reslizumab
- ClinicalTrials.gov ID
- NCT04183192
- Acronym / sponsor ID
- SCR-006
- Conditions
- Healthy Subjects, Pharmacokinetics, Pharmacodynamics
- Keywords
- Pharmacokinetics, Pharmacodynamics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- Food and Drug Administration (FDA)US federal agency
- Collaborators
- Spaulding Clinical Research LLC
- Study start
- 17 Feb 2020 (actual)
- Primary completion
- 4 Apr 2021 (actual)
- Study completion
- 4 Apr 2021 (actual)
- First posted
- 3 Dec 2019 (actual)
- Results
- Posted 22 Apr 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Detailed description
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.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 9
- Model description
- Subjects will be randomized to one of four dose groups (low, intermediate low, intermediate high, and high) of each drug (mepolizumab or reslizumab) or placebo
| Arm | Type | Receives |
|---|---|---|
| Arm A: Mepolizumab low dose | Experimental | Biological: MepolizumabSingle dose of mepolizumab 3 mg SC |
| Arm B: Mepolizumab low intermediate dose | Experimental | Biological: MepolizumabSingle dose of mepolizumab 6 mg SC |
| Arm C: Mepolizumab high intermediate dose | Experimental | Biological: MepolizumabSingle dose of mepolizumab 12 mg SC |
| Arm D: Mepolizumab high dose | Experimental | Biological: MepolizumabSingle dose of mepolizumab 24 mg SC |
| Arm E: Reslizumab low dose | Experimental | Biological: ReslizumabSingle dose of reslizumab 0.1 mg/kg IV |
| Arm F: Reslizumab intermediate low dose | Experimental | Biological: ReslizumabSingle dose of reslizumab 0.2 mg/kg IV |
| Arm G: Reslizumab high intermediate dose | Experimental | Biological: ReslizumabSingle dose of reslizumab 0.4 mg/kg IV |
| Arm H: Reslizumab high dose | Experimental | Biological: ReslizumabSingle dose of reslizumab 0.8 mg/kg IV |
| Arm I: Placebo | Placebo comparator | Biological: PlaceboSingle dose of placebo |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (29 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MepolizumabMepolizumab 3 mg administered SC | Biological | Arm A: Mepolizumab low dose |
| MepolizumabMepolizumab 6 mg administered SC | Biological | Arm B: Mepolizumab low intermediate dose |
| MepolizumabMepolizumab 12 mg administered SC | Biological | Arm C: Mepolizumab high intermediate dose |
| MepolizumabMepolizumab 24 mg administered SC | Biological | Arm D: Mepolizumab high dose |
| ReslizumabReslizumab 0.1 mg/kg administered IV | Biological | Arm E: Reslizumab low dose |
| ReslizumabReslizumab 0.2 mg/kg administered IV | Biological | Arm F: Reslizumab intermediate low dose |
| ReslizumabReslizumab 0.4 mg/kg administered IV | Biological | Arm G: Reslizumab high intermediate dose |
| ReslizumabReslizumab 0.8 mg/kg administered IV | Biological | Arm H: Reslizumab high dose |
| PlaceboPlacebo (administered either IV or SC) | Biological | Arm I: Placebo |
Primary outcome
Area Under Effect Curve (AUEC) for Eosinophils for Mepolizumab and Reslizumab
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.
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.
Maximum Change From Baseline for Eosinophils for Mepolizumab and Reslizumab
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.
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.
8 secondary outcomes
Maximum Concentration (Cmax) for 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
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
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
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
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
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
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
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 and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jennifer Deering, MSN, APNP principal investigator
Spaulding Clinical Research LLC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Mepolizumab and Reslizumab in people with Healthy Subjects and Pharmacokinetics, run by Food and Drug Administration (FDA) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Apr 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area Under Effect Curve (AUEC) for Eosinophils for Mepolizumab and Reslizumab (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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Apr 2024.