CompletedNCT04183491Updated Apr 22, 2024Results posted

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

A Phase 1 interventional study of Interferon beta-1a and Interferon beta-1a 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: 84
Allocation: Randomized
Ages: 18 Years to 55 Years
Sex: All

Study 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.

Read the detailed description

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.

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 (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.

Exclusion criteria

Exclusion Criteria:

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
- People with severe obesity (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 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.
Subject tests positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by a molecular diagnostic test performed prior to admission.
Subject has been diagnosed with any autoimmune disease or other chronic inflammatory disease.
Subject has been diagnosed with depression, suicidal ideation or psychosis.
Subject has been diagnosed with congestive heart failure.
Subject has been diagnosed with seizures of any type.
Subject has known or suspected allergies or sensitivities to any study drug.
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.
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.

Study design

Phase: Phase 1
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Double (Participant, Investigator)
Enrollment: 84 participants (actual)

Study arms

Experimental
Arm A: Interferon beta-1a low dose
Single dose of interferon beta-1a 7.5 µg intramuscular (IM)
Biological: Interferon beta-1a
Experimental
Arm B: Interferon beta-1a intermediate dose
Single dose of interferon beta-1a 15 µg IM
Biological: Interferon beta-1a
Experimental
Arm C: Interferon beta-1a high dose
Single dose of interferon beta-1a 30 µg IM
Biological: Interferon beta-1a
Experimental
Arm D: Peginterferon beta-1a low dose
Single dose of peginterferon beta-1a 31.25 µg subcutaneous (SC)
Biological: Peginterferon beta-1a
Experimental
Arm E: Peginterferon beta-1a intermediate dose
Single dose of peginterferon beta-1a 62.5 µg SC
Biological: Peginterferon beta-1a
Experimental
Arm F: Peginterferon beta-1a high dose
Single dose of peginterferon beta-1a 125 µg SC
Biological: Peginterferon beta-1a
Placebo comparator
Arm G: Placebo
Single dose of placebo
Biological: Placebo

Interventions

BiologicalInterferon beta-1a
Interferon beta-1a 7.5 µg administered IM
BiologicalInterferon beta-1a
Interferon beta-1a 15 µg administered IM
BiologicalInterferon beta-1a
Interferon beta-1a 30 µg administered IM
BiologicalPeginterferon beta-1a
Peginterferon beta-1a 31.25 µg administered SC
BiologicalPeginterferon beta-1a
Peginterferon beta-1a 62.5 µg administered SC
BiologicalPeginterferon beta-1a
Peginterferon beta-1a 125 µg administered SC
BiologicalPlacebo
Placebo (administered either IM or SC)

What researchers measure

Primary outcomes

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
Time frame: 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
Time frame: 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

Area Under the Curve (AUC) for Interferon Beta-1a and Peginterferon Beta-1a
The values and variability of pharmacokinetic characteristic (AUC of free drug concentration) at low, intermediate, and high doses of interferon beta-1a and peginterferon beta-1a
Time frame: 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
The values and variability of pharmacokinetic characteristic (Cmax) at low, intermediate, and high doses of interferon beta-1a and peginterferon beta-1a
Time frame: 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
The values and variability of standard PD metric (AUEC \[baseline subtracted\]) for MxA at low, intermediate, and high doses of interferon beta-1a and peginterferon beta-1a
Time frame: 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
The values and variability of standard PD metric (maximal difference at a single time-point) for MxA at low, intermediate, and high doses of interferon beta-1a and peginterferon beta-1a
Time frame: 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
Model parameter (Emax) for neopterin area under the effect curve models calculated after combining data from low, intermediate, and high doses of interferon beta-1a and peginterferon beta-1a with placebo data. As such, the placebo arm was included in both analyses.
Time frame: 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, ED50 (Half Maximal Effect Dose), for Neopterin Area Under the Effect Curve Models With Interferon Beta-1a or Peginterferon Beta-1a
Model parameter (ED50) for neopterin area under the effect curve models calculated after combining data from low, intermediate, and high doses of interferon beta-1a and peginterferon beta-1a with placebo data. As such, the placebo arm was included in both analyses.
Time frame: 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, for Neopterin Maximum Change From Baseline Models With Interferon Beta-1a or Peginterferon Beta-1a
Model parameter (Emax) for neopterin maximum change from baseline models calculated after combining data from low, intermediate, and high doses of interferon beta-1a and peginterferon beta-1a with placebo data. As such, the placebo arm was included in both analyses.
Time frame: 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, ED50, for Neopterin Maximum Change From Baseline Models With Interferon Beta-1a or Peginterferon Beta-1a
Model parameter (ED50) for neopterin maximum change from baseline models calculated after combining data from low, intermediate, and high doses of interferon beta-1a or peginterferon beta-1a with placebo data. As such, the placebo arm was included in both analyses.
Time frame: 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)

Results

Posted Apr 22, 2024

Participant flow

Participant flow — Overall Study
Milestone	Arm A: Interferon Beta-1a Low Dose	Arm B: Interferon Beta-1a Intermediate Dose	Arm C: Interferon Beta-1a High Dose	Arm D: Peginterferon Beta-1a Low Dose	Arm E: Peginterferon Beta-1a Intermediate Dose	Arm F: Peginterferon Beta-1a High Dose	Arm G: Placebo
Started	12	12	12	12	12	12	12
Completed	12	12	11	12	12	11	12
Not completed	0	0	1	0	0	1	0
Withdrew: Withdrawal by subject	0	0	1	0	0	1	0

Outcome measures

PrimaryArea 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

Time frame:: 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)
Reported as:: Mean · ng*day/mL

Area Under Effect Curve (AUEC) for Neopterin for Interferon Beta-1a and Peginterferon Beta-1a
ng*day/mL	Arm A: Interferon Beta-1a Low Dose	Arm B: Interferon Beta-1a Intermediate Dose	Arm C: Interferon Beta-1a High Dose	Arm D: Peginterferon Beta-1a Low Dose	Arm E: Peginterferon Beta-1a Intermediate Dose	Arm F: Peginterferon Beta-1a High Dose
Area Under Effect Curve (AUEC) for Neopterin for Interferon Beta-1a and Peginterferon Beta-1a	7.82 ± 2.87	9.61 ± 3.20	11.08 ± 5.42	11.52 ± 7.92	18.20 ± 8.80	21.59 ± 15.15

PrimaryMaximum 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

Time frame:: 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)
Reported as:: Mean · ng/mL

Maximum Change From Baseline for Neopterin for Interferon Beta-1a and Peginterferon Beta-1a
ng/mL	Arm A: Interferon Beta-1a Low Dose	Arm B: Interferon Beta-1a Intermediate Dose	Arm C: Interferon Beta-1a High Dose	Arm D: Peginterferon Beta-1a Low Dose	Arm E: Peginterferon Beta-1a Intermediate Dose	Arm F: Peginterferon Beta-1a High Dose
Maximum Change From Baseline for Neopterin for Interferon Beta-1a and Peginterferon Beta-1a	3.50 ± 1.06	4.22 ± 1.67	4.93 ± 1.85	3.17 ± 2.23	5.01 ± 2.10	5.87 ± 1.7

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

The values and variability of pharmacokinetic characteristic (AUC of free drug concentration) at low, intermediate, and high doses of interferon beta-1a and peginterferon beta-1a

Time frame:: 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)
Reported as:: Geometric mean · pg/mL*day

Area Under the Curve (AUC) for Interferon Beta-1a and Peginterferon Beta-1a
pg/mL*day	Arm A: Interferon Beta-1a Low Dose	Arm B: Interferon Beta-1a Intermediate Dose	Arm C: Interferon Beta-1a High Dose	Arm D: Peginterferon Beta-1a Low Dose	Arm E: Peginterferon Beta-1a Intermediate Dose	Arm F: Peginterferon Beta-1a High Dose
Area Under the Curve (AUC) for Interferon Beta-1a and Peginterferon Beta-1a	99.4 ± 45	223 ± 46	386 ± 28	970 ± 44	2226 ± 37	2740 ± 65

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

The values and variability of pharmacokinetic characteristic (Cmax) at low, intermediate, and high doses of interferon beta-1a and peginterferon beta-1a

Time frame:: 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)
Reported as:: Geometric mean · pg/mL

Maximum Concentration (Cmax) for Interferon Beta-1a and Peginterferon Beta-1a
pg/mL	Arm A: Interferon Beta-1a Low Dose	Arm B: Interferon Beta-1a Intermediate Dose	Arm C: Interferon Beta-1a High Dose	Arm D: Peginterferon Beta-1a Low Dose	Arm E: Peginterferon Beta-1a Intermediate Dose	Arm F: Peginterferon Beta-1a High Dose
Maximum Concentration (Cmax) for Interferon Beta-1a and Peginterferon Beta-1a	39.5 ± 54	90.8 ± 66	143 ± 33	191 ± 49	434 ± 49	509 ± 65

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

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

Time frame:: 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)
Reported as:: Mean · ng*day/mL

Area Under Effect Curve (AUEC) for Myxovirus-resistance Protein A (MxA) for Interferon Beta-1a and Peginterferon Beta-1a
ng*day/mL	Arm A: Interferon Beta-1a Low Dose	Arm B: Interferon Beta-1a Intermediate Dose	Arm C: Interferon Beta-1a High Dose	Arm D: Peginterferon Beta-1a Low Dose	Arm E: Peginterferon Beta-1a Intermediate Dose	Arm F: Peginterferon Beta-1a High Dose
Area Under Effect Curve (AUEC) for Myxovirus-resistance Protein A (MxA) for Interferon Beta-1a and Peginterferon Beta-1a	140 ± 63	172 ± 92	211 ± 102	458 ± 303	732 ± 591	1137 ± 592

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

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

Time frame:: 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)
Reported as:: Mean · ng/mL

Maximum Change From Baseline for Myxovirus-resistance Protein A (MxA) for Interferon Beta-1a and Peginterferon Beta-1a
ng/mL	Arm A: Interferon Beta-1a Low Dose	Arm B: Interferon Beta-1a Intermediate Dose	Arm C: Interferon Beta-1a High Dose	Arm D: Peginterferon Beta-1a Low Dose	Arm E: Peginterferon Beta-1a Intermediate Dose	Arm F: Peginterferon Beta-1a High Dose
Maximum Change From Baseline for Myxovirus-resistance Protein A (MxA) for Interferon Beta-1a and Peginterferon Beta-1a	52.9 ± 28.7	62.9 ± 31.7	73.4 ± 35.5	86.7 ± 49.0	117.6 ± 73.0	175.5 ± 93.5

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

Model parameter (Emax) for neopterin area under the effect curve models calculated after combining data from low, intermediate, and high doses of interferon beta-1a and peginterferon beta-1a with placebo data. As such, the placebo arm was included in both analyses.

Time frame:: 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)
Reported as:: Mean · ng/mL*day

Pharmacodynamic Model Parameter, Emax (Maximum Effect), for Neopterin Area Under the Effect Curve Models With Interferon Beta-1a or Peginterferon Beta-1a
ng/mL*day	Interferon Beta-1a: Area Under the Effect Curve Model for Neopterin	Peginterferon Beta-1a: Area Under the Effect Curve Model for Neopterin
Pharmacodynamic Model Parameter, Emax (Maximum Effect), for Neopterin Area Under the Effect Curve Models With Interferon Beta-1a or Peginterferon Beta-1a	13.3 (9.3 to 19.3)	44.0 (28.8 to 59.7)

SecondaryPharmacodynamic Model Parameter, ED50 (Half Maximal Effect Dose), for Neopterin Area Under the Effect Curve Models With Interferon Beta-1a or Peginterferon Beta-1a

Model parameter (ED50) for neopterin area under the effect curve models calculated after combining data from low, intermediate, and high doses of interferon beta-1a and peginterferon beta-1a with placebo data. As such, the placebo arm was included in both analyses.

Time frame:: 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)
Reported as:: Mean · ug

Pharmacodynamic Model Parameter, ED50 (Half Maximal Effect Dose), for Neopterin Area Under the Effect Curve Models With Interferon Beta-1a or Peginterferon Beta-1a
ug	Interferon Beta-1a: Area Under the Effect Curve Model for Neopterin	Peginterferon Beta-1a: Area Under the Effect Curve Model for Neopterin
Pharmacodynamic Model Parameter, ED50 (Half Maximal Effect Dose), for Neopterin Area Under the Effect Curve Models With Interferon Beta-1a or Peginterferon Beta-1a	4.5 (0.3 to 15.1)	84.1 (30.8 to 422.0)

SecondaryPharmacodynamic Model Parameter, Emax, for Neopterin Maximum Change From Baseline Models With Interferon Beta-1a or Peginterferon Beta-1a

Model parameter (Emax) for neopterin maximum change from baseline models calculated after combining data from low, intermediate, and high doses of interferon beta-1a and peginterferon beta-1a with placebo data. As such, the placebo arm was included in both analyses.

Time frame:: 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)
Reported as:: Mean · ng/mL

Pharmacodynamic Model Parameter, Emax, for Neopterin Maximum Change From Baseline Models With Interferon Beta-1a or Peginterferon Beta-1a
ng/mL	Interferon Beta-1a: Maximum Change From Baseline Model for Neopterin	Peginterferon Beta-1a: Maximum Change From Baseline Model for Neopterin
Pharmacodynamic Model Parameter, Emax, for Neopterin Maximum Change From Baseline Models With Interferon Beta-1a or Peginterferon Beta-1a	5.7 (4.1 to 6.3)	8.2 (5.7 to 12.4)

SecondaryPharmacodynamic Model Parameter, ED50, for Neopterin Maximum Change From Baseline Models With Interferon Beta-1a or Peginterferon Beta-1a

Model parameter (ED50) for neopterin maximum change from baseline models calculated after combining data from low, intermediate, and high doses of interferon beta-1a or peginterferon beta-1a with placebo data. As such, the placebo arm was included in both analyses.

Time frame:: 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)
Reported as:: Mean · ug

Pharmacodynamic Model Parameter, ED50, for Neopterin Maximum Change From Baseline Models With Interferon Beta-1a or Peginterferon Beta-1a
ug	Interferon Beta-1a: Maximum Change From Baseline Model for Neopterin	Peginterferon Beta-1a: Maximum Change From Baseline Model for Neopterin
Pharmacodynamic Model Parameter, ED50, for Neopterin Maximum Change From Baseline Models With Interferon Beta-1a or Peginterferon Beta-1a	4.8 (0.7 to 13.5)	44.3 (14.5 to 135.4)

Adverse events

Collected over 6 days for subjects in interferon beta-1a arms and 13 days for subjects in peginterferon beta-1a or placebo treatment arms. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Arm A: Interferon Beta-1a Low Dose	0/12 (0%)	0/12 (0%)	7/12 (58.3%)
Arm B: Interferon Beta-1a Intermediate Dose	0/12 (0%)	0/12 (0%)	7/12 (58.3%)
Arm C: Interferon Beta-1a High Dose	0/12 (0%)	0/12 (0%)	10/12 (83.3%)
Arm D: Peginterferon Beta-1a Low Dose	0/12 (0%)	0/12 (0%)	7/12 (58.3%)
Arm E: Peginterferon Beta-1a Intermediate Dose	0/12 (0%)	0/12 (0%)	9/12 (75%)
Arm F: Peginterferon Beta-1a High Dose	0/12 (0%)	0/12 (0%)	11/12 (91.7%)
Arm G: Placebo	0/12 (0%)	0/12 (0%)	4/12 (33.3%)

Most frequent other events

Showing 10 of 40

Most frequent other events
Event	Arm A: Interferon Beta-1a Low Dose	Arm B: Interferon Beta-1a Intermediate Dose	Arm C: Interferon Beta-1a High Dose	Arm D: Peginterferon Beta-1a Low Dose	Arm E: Peginterferon Beta-1a Intermediate Dose	Arm F: Peginterferon Beta-1a High Dose	Arm G: Placebo
HeadacheNervous system disorders	3/12	5/12	8/12	2/12	5/12	9/12	1/12
MyalgiaMusculoskeletal and connective tissue disorders	3/12	4/12	4/12	2/12	5/12	5/12	1/12
ChillsGeneral disorders	2/12	1/12	3/12	2/12	3/12	5/12	0/12
Injection site erythemaGeneral disorders	0/12	0/12	0/12	2/12	1/12	5/12	0/12
NauseaGastrointestinal disorders	0/12	1/12	3/12	0/12	0/12	3/12	0/12
FatigueGeneral disorders	0/12	0/12	1/12	0/12	1/12	3/12	0/12
DizzinessNervous system disorders	2/12	0/12	1/12	1/12	1/12	2/12	0/12
Vessel puncture site painGeneral disorders	0/12	1/12	1/12	1/12	2/12	0/12	1/12
PyrexiaGeneral disorders	0/12	2/12	2/12	0/12	2/12	0/12	0/12
Skin irritationSkin and subcutaneous tissue disorders	0/12	0/12	0/12	1/12	2/12	0/12	0/12

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Arm A: Interferon Beta-1a Low Dose	Arm B: Interferon Beta-1a Intermediate Dose	Arm C: Interferon Beta-1a High Dose	Arm D: Peginterferon Beta-1a Low Dose	Arm E: Peginterferon Beta-1a Intermediate Dose	Arm F: Peginterferon Beta-1a High Dose	Arm G: Placebo	Total
Mean	36.0 ± 8.6	35.1 ± 9.7	38.3 ± 10.9	37.7 ± 12.7	31.9 ± 11.1	35.5 ± 8.0	36.9 ± 10.6	35.9 ± 10.2

Sex: Female, Male
Sex: Female, Male(Participants)	Arm A: Interferon Beta-1a Low Dose	Arm B: Interferon Beta-1a Intermediate Dose	Arm C: Interferon Beta-1a High Dose	Arm D: Peginterferon Beta-1a Low Dose	Arm E: Peginterferon Beta-1a Intermediate Dose	Arm F: Peginterferon Beta-1a High Dose	Arm G: Placebo	Total
Female	5	5	4	5	5	4	4	32
Male	7	7	8	7	7	8	8	52

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Arm A: Interferon Beta-1a Low Dose	Arm B: Interferon Beta-1a Intermediate Dose	Arm C: Interferon Beta-1a High Dose	Arm D: Peginterferon Beta-1a Low Dose	Arm E: Peginterferon Beta-1a Intermediate Dose	Arm F: Peginterferon Beta-1a High Dose	Arm G: Placebo	Total
Hispanic or Latino	3	1	0	3	1	1	1	10
Not Hispanic or Latino	9	11	12	9	11	11	11	74
Unknown or Not Reported	0	0	0	0	0	0	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Arm A: Interferon Beta-1a Low Dose	Arm B: Interferon Beta-1a Intermediate Dose	Arm C: Interferon Beta-1a High Dose	Arm D: Peginterferon Beta-1a Low Dose	Arm E: Peginterferon Beta-1a Intermediate Dose	Arm F: Peginterferon Beta-1a High Dose	Arm G: Placebo	Total
American Indian or Alaska Native	0	0	0	0	0	0	0	0
Asian	2	0	0	0	0	0	0	2
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0	0
Black or African American	2	8	7	6	8	4	6	41
White	8	3	4	6	4	8	5	38
More than one race	0	1	1	0	0	0	1	3
Unknown or Not Reported	0	0	0	0	0	0	0	0

Region of Enrollment
Region of Enrollment(participants)	Arm A: Interferon Beta-1a Low Dose	Arm B: Interferon Beta-1a Intermediate Dose	Arm C: Interferon Beta-1a High Dose	Arm D: Peginterferon Beta-1a Low Dose	Arm E: Peginterferon Beta-1a Intermediate Dose	Arm F: Peginterferon Beta-1a High Dose	Arm G: Placebo	Total
United States	12	12	12	12	12	12	12	84

Body weight
Body weight(kg)	Arm A: Interferon Beta-1a Low Dose	Arm B: Interferon Beta-1a Intermediate Dose	Arm C: Interferon Beta-1a High Dose	Arm D: Peginterferon Beta-1a Low Dose	Arm E: Peginterferon Beta-1a Intermediate Dose	Arm F: Peginterferon Beta-1a High Dose	Arm G: Placebo	Total
Mean	73.5 ± 11.4	72.7 ± 12.2	80.0 ± 14.5	78.5 ± 10.7	76.3 ± 13.2	76.3 ± 10.9	79.3 ± 9.1	76.7 ± 11.7

Body mass index
Body mass index(kg/m^2)	Arm A: Interferon Beta-1a Low Dose	Arm B: Interferon Beta-1a Intermediate Dose	Arm C: Interferon Beta-1a High Dose	Arm D: Peginterferon Beta-1a Low Dose	Arm E: Peginterferon Beta-1a Intermediate Dose	Arm F: Peginterferon Beta-1a High Dose	Arm G: Placebo	Total
Mean	24.5 ± 2.3	25.9 ± 2.7	27.0 ± 3.0	26.2 ± 3.2	27.0 ± 2.6	25.6 ± 2.5	27.1 ± 2.4	26.2 ± 2.7

Study locations

1 site

Spaulding Clinical Research
West Bend, Wisconsin 53095, United States

References and documents

Study documents

Study protocol · Aug 17, 2020
Statistical analysis plan · Jul 26, 2021
Informed consent form · Nov 5, 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: NCT04183491
Lead sponsor: Food and Drug Administration (FDA)
Collaborators: Spaulding Clinical Research LLC
Responsible party: Sponsor
First posted: Dec 3, 2019
Start date: Feb 28, 2020
Primary completion: Jan 26, 2021
Completion: Jan 26, 2021
Results posted: Apr 22, 2024
Last update: Apr 22, 2024

Study contacts

Carlos Sanabria, MD

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 ↗

Not currently enrolling

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

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies from this sponsor

Food and Drug Administration (FDA)

Start the discussion