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

NCT04183491 | Completed Phase 1 Results FDA Drug

• 1 other identifier: SCR-008
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Subjects; Pharmacokinetics; Pharmacodynamics

Keywords

Pharmacokinetics; Pharmacodynamics

Outcome Measures

Primary Outcomes (2)

• Area Under Effect Curve (AUEC) for Neopterin for Interferon Beta-1a and Peginterferon Beta-1a

  The values and variability of standard pharmacodynamic (PD) metric (AUEC \[baseline subtracted\]) for neopterin at low, intermediate, and high doses of interferon beta-1a and peginterferon beta-1a

  0, 1, 3, 6, 8, 16, 24, 32, 40, 48, 72, hours post-dose; once daily from Day 4 onwards until 7 days post-dose for Interferon Beta-1a treatment arms (Arms A, B and C) and 14 days post-dose for Peginterferon Beta-1a treatment arms (Arms D, E, and F)

• Maximum Change From Baseline for Neopterin for Interferon Beta-1a and Peginterferon Beta-1a

  The values and variability of standard pharmacodynamic (PD) metric (maximal difference at a single time-point) for neopterin at low, intermediate, and high doses of interferon beta-1a and peginterferon beta-1a

  0, 1, 3, 6, 8, 16, 24, 32, 40, 48, 72, hours post-dose; once daily from Day 4 onwards until 7 days post-dose for Interferon Beta-1a treatment arms (Arms A, B and C) and 14 days post-dose for Peginterferon Beta-1a treatment arms (Arms D, E, and F)

Secondary Outcomes (8)

• Area Under the Curve (AUC) for Interferon Beta-1a and Peginterferon Beta-1a

  0, 1, 3, 6, 8, 16, 24, 32, 40, 48, 72, hours post-dose; once daily from Day 4 onwards until 7 days post-dose for Interferon Beta-1a treatment arms (Arms A, B and C) and 14 days post-dose for Peginterferon Beta-1a treatment arms (Arms D, E, and F)

• Maximum Concentration (Cmax) for Interferon Beta-1a and Peginterferon Beta-1a

  0, 1, 3, 6, 8, 16, 24, 32, 40, 48, 72, hours post-dose; once daily from Day 4 onwards until 7 days post-dose for Interferon Beta-1a treatment arms (Arms A, B and C) and 14 days post-dose for Peginterferon Beta-1a treatment arms (Arms D, E, and F)

• Area Under Effect Curve (AUEC) for Myxovirus-resistance Protein A (MxA) for Interferon Beta-1a and Peginterferon Beta-1a

  0, 1, 3, 6, 8, 16, 24, 32, 40, 48, 72, hours post-dose; once daily from Day 4 onwards until 7 days post-dose for Interferon Beta-1a treatment arms (Arms A, B and C) and 14 days post-dose for Peginterferon Beta-1a treatment arms (Arms D, E, and F)

• Maximum Change From Baseline for Myxovirus-resistance Protein A (MxA) for Interferon Beta-1a and Peginterferon Beta-1a

  0, 1, 3, 6, 8, 16, 24, 32, 40, 48, 72, hours post-dose; once daily from Day 4 onwards until 7 days post-dose for Interferon Beta-1a treatment arms (Arms A, B and C) and 14 days post-dose for Peginterferon Beta-1a treatment arms (Arms D, E, and F)

• Pharmacodynamic Model Parameter, Emax (Maximum Effect), for Neopterin Area Under the Effect Curve Models With Interferon Beta-1a or Peginterferon Beta-1a

  0, 1, 3, 6, 8, 16, 24, 32, 40, 48, 72, hours post-dose; once daily from Day 4 onwards until 7 days post-dose for Interferon Beta-1a treatment arms (Arms A, B and C) and 14 days post-dose for Peginterferon Beta-1a treatment arms (Arms D, E, and F)

Study Arms (7)

Arm A: Interferon beta-1a low dose

EXPERIMENTAL

Single dose of interferon beta-1a 7.5 µg intramuscular (IM)

Biological: Interferon beta-1a

Arm B: Interferon beta-1a intermediate dose

EXPERIMENTAL

Single dose of interferon beta-1a 15 µg IM

Biological: Interferon beta-1a

Arm C: Interferon beta-1a high dose

EXPERIMENTAL

Single dose of interferon beta-1a 30 µg IM

Biological: Interferon beta-1a

Arm D: Peginterferon beta-1a low dose

EXPERIMENTAL

Single dose of peginterferon beta-1a 31.25 µg subcutaneous (SC)

Biological: Peginterferon beta-1a

Arm E: Peginterferon beta-1a intermediate dose

EXPERIMENTAL

Single dose of peginterferon beta-1a 62.5 µg SC

Biological: Peginterferon beta-1a

Arm F: Peginterferon beta-1a high dose

EXPERIMENTAL

Single dose of peginterferon beta-1a 125 µg SC

Biological: Peginterferon beta-1a

Arm G: Placebo

PLACEBO COMPARATOR

Single dose of placebo

Biological: Placebo

Interventions

Interferon beta-1a BIOLOGICAL

Interferon beta-1a 7.5 µg administered IM

Arm A: Interferon beta-1a low dose

Peginterferon beta-1a BIOLOGICAL

Peginterferon beta-1a 31.25 µg administered SC

Arm D: Peginterferon beta-1a low dose

Placebo BIOLOGICAL

Placebo (administered either IM or SC)

Arm G: Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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).
• 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.
• Female subjects must not be pregnant or lactating before enrollment in 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 study
• Subject is highly likely (as determined by the investigator) to comply with the protocol defined procedures and to complete the study.

You may not qualify if:

• Subject has had previous exposure to the biologic Avonex or Plegridy.
• 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.
• 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 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

Sponsors & Collaborators

• Food and Drug Administration (FDA): lead
• Spaulding Clinical Research LLC: collaborator

Study Sites (1)

Spaulding Clinical Research

West Bend, Wisconsin, 53095, United States

Location

MeSH Terms

Interventions

Interferon beta-1a; peginterferon beta-1a

Intervention Hierarchy (Ancestors)

Interferon-beta; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: David Strauss, MD, PhD
• Organization: U.S. Food and Drug Administration

David.Strauss@fda.hhs.gov

301-796-6323

Study Officials

• Carlos Sanabria, MD

  Spaulding Clinical Research LLC

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: 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.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: November 27, 2019
• First Posted: December 3, 2019
• Study Start: February 28, 2020
• Primary Completion: January 26, 2021
• Study Completion: January 26, 2021
• Last Updated: April 22, 2024
• Results First Posted: April 22, 2024

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: February, 2022. Materials will be available indefinitely.

Locations

US (1)