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Pharmacodynamic Biomarkers to Support Biosimilar Development: Interferon Beta-1A Products

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ClinicalTrials.gov Identifier: NCT04183491
Recruitment Status : Recruiting
First Posted : December 3, 2019
Last Update Posted : January 20, 2021
Sponsor:
Collaborator:
Spaulding Clinical Research LLC
Information provided by (Responsible Party):
Food and Drug Administration (FDA)

Brief Summary:

This study is designed to assess pharmacokinetics and pharmacodynamics of interferon beta-1a and peginterferon beta-1a 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 84 healthy subjects assigned to one of three dose groups (low, intermediate, and high) of each drug (interferon beta-1a and peginterferon beta-1a) or placebo.


Condition or disease Intervention/treatment Phase
Healthy Subjects Pharmacokinetics Pharmacodynamics Biological: Interferon beta-1a Biological: Peginterferon beta-1a Biological: Placebo Phase 1

Detailed Description:

This study is designed to assess pharmacokinetics and pharmacodynamics of interferon beta-1a and peginterferon beta-1a 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 84 healthy subjects assigned to one of three dose groups (low, intermediate, and high) of each drug (interferon beta-1a and peginterferon beta-1a) or placebo. Interferon beta-1a doses are 7.5, 15, and 30 µg. Peginterferon beta-1a doses are 31.25, 62.5, and 125 µg. Each arm will include 12 subjects (6 male and 6 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 7 days (interferon beta-1a) or 14 days (peginterferon beta-1a and placebo).

Blood samples (approximately 5 mL per sample) will be collected for determination of plasma concentrations for study drug and neopterin levels. Additional blood samples will be collected for determination of lipids (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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 84 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Subjects will be randomized to one of three dose groups (low, intermediate, and high) of each drug (interferon beta-1a and peginterferon beta-1a) or placebo
Masking: Double (Participant, Investigator)
Masking Description:

The pharmacist (and designated staff member responsible for confirmation of study drug dose) will be unblinded to subject treatment assignment; however, the pharmacist will not perform any study procedures other than study drug preparation and dispensing.

Subjects and staff will be blinded to treatment assignment during confinement, but route of administration will not be blinded. The blind will be maintained through a randomization schedule held by the dispensing pharmacist. Subjects and staff will be informed of a subject's end of study day when discharged from confinement. Subjects and staff will not be informed of the specific treatment arm assignment. The clinical research nurse will administer the subcutaneous study drug in unit dose containers that are not transparent.

Primary Purpose: Other
Official Title: Pharmacodynamic Biomarkers to Support Biosimilar Development: Clinical Study 3 - Interferon Beta-1A and Peginterferon Beta-1A
Actual Study Start Date : February 19, 2020
Estimated Primary Completion Date : February 2021
Estimated Study Completion Date : February 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm A: Interferon beta-1a low dose
Single dose of interferon beta-1a 7.5 µg intramuscular (IM)
Biological: Interferon beta-1a
Interferon beta-1a 7.5 µg administered IM

Experimental: Arm B: Interferon beta-1a intermediate dose
Single dose of interferon beta-1a 15 µg IM
Biological: Interferon beta-1a
Interferon beta-1a 15 µg administered IM

Experimental: Arm C: Interferon beta-1a high dose
Single dose of interferon beta-1a 30 µg IM
Biological: Interferon beta-1a
Interferon beta-1a 30 µg administered IM

Experimental: Arm D: Peginterferon beta-1a low dose
Single dose of peginterferon beta-1a 31.25 µg subcutaneous (SC)
Biological: Peginterferon beta-1a
Peginterferon beta-1a 31.25 µg administered SC

Experimental: Arm E: Peginterferon beta-1a intermediate dose
Single dose of peginterferon beta-1a 62.5 µg SC
Biological: Peginterferon beta-1a
Peginterferon beta-1a 62.5 µg administered SC

Experimental: Arm F: Peginterferon beta-1a high dose
Single dose of peginterferon beta-1a 125 µg SC
Biological: Peginterferon beta-1a
Peginterferon beta-1a 125 µg administered SC

Placebo Comparator: Arm G: Placebo
Single dose of placebo
Biological: Placebo
Placebo (administered either IM or SC)




Primary Outcome Measures :
  1. Area under effect curve (AUEC) and maximum change from baseline for neopterin for interferon beta-1a and peginterferon beta-1a [ Time Frame: 7 or 14 days, depending on treatment arm ]
    The values and variability of standard pharmacodynamic (PD) metrics (AUEC and maximal difference at a single time-point) for neopterin at low, intermediate, and high doses of interferon beta-1a and peginterferon beta-1a


Secondary Outcome Measures :
  1. Maximum concentration (Cmax) and area under the curve (AUC) for interferon beta-1a and peginterferon beta-1a [ Time Frame: 7 or 14 days, depending on treatment arm ]
    2. The values and variability of pharmacokinetic characteristics (Cmax and AUC of free drug concentration) at low, intermediate, and high doses of interferon beta-1a and peginterferon beta-1a

  2. Area under effect curve and maximum change from baseline for Myxovirus-resistance protein A (MxA) for interferon beta-1a and peginterferon beta-1a [ Time Frame: 7 or 14 days, depending on treatment arm ]
    1. The values and variability of standard PD metrics (AUEC and maximal difference at a single time-point) for MxA at low, intermediate, and high doses of interferon beta-1a and peginterferon beta-1a

  3. Pharmacodynamic model parameters for interferon beta-1a and peginterferon beta-1a [ Time Frame: 7 or 14 days, depending on treatment arm ]
    3. Parameters (Emax [maximum effect], and EC50 [half maximal effect concentration]) calculated by the model after combining data from low, intermediate, and high doses of interferon beta-1a and peginterferon beta-1a with placebo data



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Subject signs an institutional review board (IRB) 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.
  2. 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.
  3. 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).
  4. Subject must have a negative test result for alcohol and drugs of abuse at screening and Check-in (Day -1).
  5. 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 1 month 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 last application of study drug.
  6. Female subjects must not be pregnant or lactating before enrollment in the study.
  7. 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 study
  8. Subject is highly likely (as determined by the investigator) to comply with the protocol defined procedures and to complete the study.

Exclusion Criteria:

  1. Subject has had previous exposure to the biologic Avonex or Plegridy.
  2. Subject is anemic (i.e., with Hct or Hgb considered clinically significant by Investigator or chronic history of anemia) or has any chronic condition(s) that may impact blood sample collection.
  3. Subject has a history of asthma.
  4. Subject has a history of anaphylaxis from environmental exposures such as peanuts or bee stings.
  5. Subject has an allergic history that includes urticaria, angioedema or respiratory coughing or bronchospasm.
  6. Subject has a history of severe local reactions or generalized erythema from skin allergen testing.
  7. 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.
  8. 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.
  9. Subject has used nicotine-containing products (e.g., cigarettes, cigars, chewing tobacco, snuff) within 6 weeks of Screening.
  10. 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.
  11. 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 (BMI of 40 or higher)
    • People with diabetes
    • People with chronic kidney disease undergoing dialysis
    • People with liver disease
  12. Subject has any signs or symptoms that are consistent with COVID-19. Per current CDC recommendations, this includes subjects with the symptoms of 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.
  13. Subject tests positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by a molecular diagnostic test performed prior to admission.
  14. Subject has been diagnosed with any autoimmune disease or other chronic inflammatory disease.
  15. Subject has been diagnosed with depression, suicidal ideation or psychosis.
  16. Subject has been diagnosed with congestive heart failure.
  17. Subject has been diagnosed with seizures of any type.
  18. Subject has known or suspected allergies or sensitivities to any study drug.
  19. Subject has clinical laboratory test results (hematology, serum chemistry lipid panel and comprehensive metabolic panel) at Screening that are outside the reference ranges provided by the clinical laboratory and considered clinically significant by the investigator.
  20. Subject has a positive test result at Screening for HIV 1 or 2 antibody, hepatitis C virus antibodies, or hepatitis B surface antigen.
  21. Subject is unable or unwilling to undergo multiple venipunctures for blood sample collection because of poor tolerability or poor venous access.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04183491


Contacts
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Contact: Jennifer Nehls 608.320.4075 Jennifer.nehls@spauldingclinical.com

Locations
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United States, Wisconsin
Spaulding Clinical Research Recruiting
West Bend, Wisconsin, United States, 53095
Contact: Jennifer Nehls    608-320-4075    Jennifer.nehls@spauldingclinical.com   
Sponsors and Collaborators
Food and Drug Administration (FDA)
Spaulding Clinical Research LLC
Investigators
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Principal Investigator: Carlos Sanabria, MD Spaulding Clinical Research LLC
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Responsible Party: Food and Drug Administration (FDA)
ClinicalTrials.gov Identifier: NCT04183491    
Other Study ID Numbers: SCR-008
First Posted: December 3, 2019    Key Record Dates
Last Update Posted: January 20, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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 Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: February, 2022. Materials will be available indefinitely.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Food and Drug Administration (FDA):
Pharmacokinetics
Pharmacodynamics
Additional relevant MeSH terms:
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Interferons
Interferon-beta
Interferon beta-1a
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs
Adjuvants, Immunologic