Trial Outcomes & Findings for Pharmacodynamic Biomarkers to Support Biosimilar Development: Interferon Beta-1A Products (NCT NCT04183491)

Last Updated: 2024-04-22

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

84 participants

Primary outcome timeframe

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 on

2024-04-22

Participant Flow

Participant milestones

Participant milestones
Measure	Arm A: Interferon Beta-1a Low Dose Single dose of interferon beta-1a 7.5 µg intramuscular (IM) Interferon beta-1a: Interferon beta-1a 7.5 µg administered IM	Arm B: Interferon Beta-1a Intermediate Dose Single dose of interferon beta-1a 15 µg IM Interferon beta-1a: Interferon beta-1a 15 µg administered IM	Arm C: Interferon Beta-1a High Dose Single dose of interferon beta-1a 30 µg IM Interferon beta-1a: Interferon beta-1a 30 µg administered IM	Arm D: Peginterferon Beta-1a Low Dose Single dose of peginterferon beta-1a 31.25 µg subcutaneous (SC) Peginterferon beta-1a: Peginterferon beta-1a 31.25 µg administered SC	Arm E: Peginterferon Beta-1a Intermediate Dose Single dose of peginterferon beta-1a 62.5 µg SC Peginterferon beta-1a: Peginterferon beta-1a 62.5 µg administered SC	Arm F: Peginterferon Beta-1a High Dose Single dose of peginterferon beta-1a 125 µg SC Peginterferon beta-1a: Peginterferon beta-1a 125 µg administered SC	Arm G: Placebo Single dose of placebo Placebo: Placebo (administered either IM or SC)
Overall Study STARTED	12	12	12	12	12	12	12
Overall Study COMPLETED	12	12	11	12	12	11	12
Overall Study NOT COMPLETED	0	0	1	0	0	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A: Interferon Beta-1a Low Dose Single dose of interferon beta-1a 7.5 µg intramuscular (IM) Interferon beta-1a: Interferon beta-1a 7.5 µg administered IM	Arm B: Interferon Beta-1a Intermediate Dose Single dose of interferon beta-1a 15 µg IM Interferon beta-1a: Interferon beta-1a 15 µg administered IM	Arm C: Interferon Beta-1a High Dose Single dose of interferon beta-1a 30 µg IM Interferon beta-1a: Interferon beta-1a 30 µg administered IM	Arm D: Peginterferon Beta-1a Low Dose Single dose of peginterferon beta-1a 31.25 µg subcutaneous (SC) Peginterferon beta-1a: Peginterferon beta-1a 31.25 µg administered SC	Arm E: Peginterferon Beta-1a Intermediate Dose Single dose of peginterferon beta-1a 62.5 µg SC Peginterferon beta-1a: Peginterferon beta-1a 62.5 µg administered SC	Arm F: Peginterferon Beta-1a High Dose Single dose of peginterferon beta-1a 125 µg SC Peginterferon beta-1a: Peginterferon beta-1a 125 µg administered SC	Arm G: Placebo Single dose of placebo Placebo: Placebo (administered either IM or SC)
Overall Study Withdrawal by Subject	0	0	1	0	0	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A: Interferon Beta-1a Low Dose n=12 Participants Single dose of interferon beta-1a 7.5 µg intramuscular (IM) Interferon beta-1a: Interferon beta-1a 7.5 µg administered IM	Arm B: Interferon Beta-1a Intermediate Dose n=12 Participants Single dose of interferon beta-1a 15 µg IM Interferon beta-1a: Interferon beta-1a 15 µg administered IM	Arm C: Interferon Beta-1a High Dose n=12 Participants Single dose of interferon beta-1a 30 µg IM Interferon beta-1a: Interferon beta-1a 30 µg administered IM	Arm D: Peginterferon Beta-1a Low Dose n=12 Participants Single dose of peginterferon beta-1a 31.25 µg subcutaneous (SC) Peginterferon beta-1a: Peginterferon beta-1a 31.25 µg administered SC	Arm E: Peginterferon Beta-1a Intermediate Dose n=12 Participants Single dose of peginterferon beta-1a 62.5 µg SC Peginterferon beta-1a: Peginterferon beta-1a 62.5 µg administered SC	Arm F: Peginterferon Beta-1a High Dose n=12 Participants Single dose of peginterferon beta-1a 125 µg SC Peginterferon beta-1a: Peginterferon beta-1a 125 µg administered SC	Arm G: Placebo n=12 Participants Single dose of placebo Placebo: Placebo (administered either IM or SC)	Total n=84 Participants Total of all reporting groups
Age, Continuous	36.0 years STANDARD_DEVIATION 8.6 • n=99 Participants	35.1 years STANDARD_DEVIATION 9.7 • n=107 Participants	38.3 years STANDARD_DEVIATION 10.9 • n=206 Participants	37.7 years STANDARD_DEVIATION 12.7 • n=7 Participants	31.9 years STANDARD_DEVIATION 11.1 • n=31 Participants	35.5 years STANDARD_DEVIATION 8.0 • n=30 Participants	36.9 years STANDARD_DEVIATION 10.6 • n=3 Participants	35.9 years STANDARD_DEVIATION 10.2 • n=6 Participants
Sex: Female, Male Female	5 Participants n=99 Participants	5 Participants n=107 Participants	4 Participants n=206 Participants	5 Participants n=7 Participants	5 Participants n=31 Participants	4 Participants n=30 Participants	4 Participants n=3 Participants	32 Participants n=6 Participants
Sex: Female, Male Male	7 Participants n=99 Participants	7 Participants n=107 Participants	8 Participants n=206 Participants	7 Participants n=7 Participants	7 Participants n=31 Participants	8 Participants n=30 Participants	8 Participants n=3 Participants	52 Participants n=6 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=99 Participants	1 Participants n=107 Participants	0 Participants n=206 Participants	3 Participants n=7 Participants	1 Participants n=31 Participants	1 Participants n=30 Participants	1 Participants n=3 Participants	10 Participants n=6 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=99 Participants	11 Participants n=107 Participants	12 Participants n=206 Participants	9 Participants n=7 Participants	11 Participants n=31 Participants	11 Participants n=30 Participants	11 Participants n=3 Participants	74 Participants n=6 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	0 Participants n=3 Participants	0 Participants n=6 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	0 Participants n=3 Participants	0 Participants n=6 Participants
Race (NIH/OMB) Asian	2 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	0 Participants n=3 Participants	2 Participants n=6 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	0 Participants n=3 Participants	0 Participants n=6 Participants
Race (NIH/OMB) Black or African American	2 Participants n=99 Participants	8 Participants n=107 Participants	7 Participants n=206 Participants	6 Participants n=7 Participants	8 Participants n=31 Participants	4 Participants n=30 Participants	6 Participants n=3 Participants	41 Participants n=6 Participants
Race (NIH/OMB) White	8 Participants n=99 Participants	3 Participants n=107 Participants	4 Participants n=206 Participants	6 Participants n=7 Participants	4 Participants n=31 Participants	8 Participants n=30 Participants	5 Participants n=3 Participants	38 Participants n=6 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	1 Participants n=3 Participants	3 Participants n=6 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	0 Participants n=3 Participants	0 Participants n=6 Participants
Region of Enrollment United States	12 participants n=99 Participants	12 participants n=107 Participants	12 participants n=206 Participants	12 participants n=7 Participants	12 participants n=31 Participants	12 participants n=30 Participants	12 participants n=3 Participants	84 participants n=6 Participants
Body weight	73.5 kg STANDARD_DEVIATION 11.4 • n=99 Participants	72.7 kg STANDARD_DEVIATION 12.2 • n=107 Participants	80.0 kg STANDARD_DEVIATION 14.5 • n=206 Participants	78.5 kg STANDARD_DEVIATION 10.7 • n=7 Participants	76.3 kg STANDARD_DEVIATION 13.2 • n=31 Participants	76.3 kg STANDARD_DEVIATION 10.9 • n=30 Participants	79.3 kg STANDARD_DEVIATION 9.1 • n=3 Participants	76.7 kg STANDARD_DEVIATION 11.7 • n=6 Participants
Body mass index	24.5 kg/m^2 STANDARD_DEVIATION 2.3 • n=99 Participants	25.9 kg/m^2 STANDARD_DEVIATION 2.7 • n=107 Participants	27.0 kg/m^2 STANDARD_DEVIATION 3.0 • n=206 Participants	26.2 kg/m^2 STANDARD_DEVIATION 3.2 • n=7 Participants	27.0 kg/m^2 STANDARD_DEVIATION 2.6 • n=31 Participants	25.6 kg/m^2 STANDARD_DEVIATION 2.5 • n=30 Participants	27.1 kg/m^2 STANDARD_DEVIATION 2.4 • n=3 Participants	26.2 kg/m^2 STANDARD_DEVIATION 2.7 • n=6 Participants

PRIMARY outcome

Timeframe: 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)

Population: Analysis population includes all subjects who did not discontinue before the end of study.

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

Outcome measures

Outcome measures
Measure	Arm A: Interferon Beta-1a Low Dose n=12 Participants Single dose of interferon beta-1a 7.5 µg intramuscular (IM) Interferon beta-1a: Interferon beta-1a 7.5 µg administered IM	Arm B: Interferon Beta-1a Intermediate Dose n=12 Participants Single dose of interferon beta-1a 15 µg IM Interferon beta-1a: Interferon beta-1a 15 µg administered IM	Arm C: Interferon Beta-1a High Dose n=11 Participants Single dose of interferon beta-1a 30 µg IM Interferon beta-1a: Interferon beta-1a 30 µg administered IM	Arm D: Peginterferon Beta-1a Low Dose n=12 Participants Single dose of peginterferon beta-1a 31.25 µg subcutaneous (SC) Peginterferon beta-1a: Peginterferon beta-1a 31.25 µg administered SC	Arm E: Peginterferon Beta-1a Intermediate Dose n=12 Participants Single dose of peginterferon beta-1a 62.5 µg SC Peginterferon beta-1a: Peginterferon beta-1a 62.5 µg administered SC	Arm F: Peginterferon Beta-1a High Dose n=11 Participants Single dose of peginterferon beta-1a 125 µg SC Peginterferon beta-1a: Peginterferon beta-1a 125 µg administered SC
Area Under Effect Curve (AUEC) for Neopterin for Interferon Beta-1a and Peginterferon Beta-1a	7.82 ng*day/mL Standard Deviation 2.87	9.61 ng*day/mL Standard Deviation 3.20	11.08 ng*day/mL Standard Deviation 5.42	11.52 ng*day/mL Standard Deviation 7.92	18.20 ng*day/mL Standard Deviation 8.80	21.59 ng*day/mL Standard Deviation 15.15

PRIMARY outcome

Population: Analysis population includes all subjects who did not discontinue before the end of study.

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

Outcome measures

Outcome measures
Measure	Arm A: Interferon Beta-1a Low Dose n=12 Participants Single dose of interferon beta-1a 7.5 µg intramuscular (IM) Interferon beta-1a: Interferon beta-1a 7.5 µg administered IM	Arm B: Interferon Beta-1a Intermediate Dose n=12 Participants Single dose of interferon beta-1a 15 µg IM Interferon beta-1a: Interferon beta-1a 15 µg administered IM	Arm C: Interferon Beta-1a High Dose n=11 Participants Single dose of interferon beta-1a 30 µg IM Interferon beta-1a: Interferon beta-1a 30 µg administered IM	Arm D: Peginterferon Beta-1a Low Dose n=12 Participants Single dose of peginterferon beta-1a 31.25 µg subcutaneous (SC) Peginterferon beta-1a: Peginterferon beta-1a 31.25 µg administered SC	Arm E: Peginterferon Beta-1a Intermediate Dose n=12 Participants Single dose of peginterferon beta-1a 62.5 µg SC Peginterferon beta-1a: Peginterferon beta-1a 62.5 µg administered SC	Arm F: Peginterferon Beta-1a High Dose n=11 Participants Single dose of peginterferon beta-1a 125 µg SC Peginterferon beta-1a: Peginterferon beta-1a 125 µg administered SC
Maximum Change From Baseline for Neopterin for Interferon Beta-1a and Peginterferon Beta-1a	3.50 ng/mL Standard Deviation 1.06	4.22 ng/mL Standard Deviation 1.67	4.93 ng/mL Standard Deviation 1.85	3.17 ng/mL Standard Deviation 2.23	5.01 ng/mL Standard Deviation 2.10	5.87 ng/mL Standard Deviation 1.7

SECONDARY outcome

Population: Analysis population includes all subjects who did not discontinue before the end of study.

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

Outcome measures

Outcome measures
Measure	Arm A: Interferon Beta-1a Low Dose n=12 Participants Single dose of interferon beta-1a 7.5 µg intramuscular (IM) Interferon beta-1a: Interferon beta-1a 7.5 µg administered IM	Arm B: Interferon Beta-1a Intermediate Dose n=12 Participants Single dose of interferon beta-1a 15 µg IM Interferon beta-1a: Interferon beta-1a 15 µg administered IM	Arm C: Interferon Beta-1a High Dose n=11 Participants Single dose of interferon beta-1a 30 µg IM Interferon beta-1a: Interferon beta-1a 30 µg administered IM	Arm D: Peginterferon Beta-1a Low Dose n=12 Participants Single dose of peginterferon beta-1a 31.25 µg subcutaneous (SC) Peginterferon beta-1a: Peginterferon beta-1a 31.25 µg administered SC	Arm E: Peginterferon Beta-1a Intermediate Dose n=12 Participants Single dose of peginterferon beta-1a 62.5 µg SC Peginterferon beta-1a: Peginterferon beta-1a 62.5 µg administered SC	Arm F: Peginterferon Beta-1a High Dose n=11 Participants Single dose of peginterferon beta-1a 125 µg SC Peginterferon beta-1a: Peginterferon beta-1a 125 µg administered SC
Area Under the Curve (AUC) for Interferon Beta-1a and Peginterferon Beta-1a	99.4 pg/mL*day Geometric Coefficient of Variation 45	223 pg/mL*day Geometric Coefficient of Variation 46	386 pg/mL*day Geometric Coefficient of Variation 28	970 pg/mL*day Geometric Coefficient of Variation 44	2226 pg/mL*day Geometric Coefficient of Variation 37	2740 pg/mL*day Geometric Coefficient of Variation 65

SECONDARY outcome

Population: Analysis population includes all subjects who did not discontinue before the end of study.

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

Outcome measures

Outcome measures
Measure	Arm A: Interferon Beta-1a Low Dose n=12 Participants Single dose of interferon beta-1a 7.5 µg intramuscular (IM) Interferon beta-1a: Interferon beta-1a 7.5 µg administered IM	Arm B: Interferon Beta-1a Intermediate Dose n=12 Participants Single dose of interferon beta-1a 15 µg IM Interferon beta-1a: Interferon beta-1a 15 µg administered IM	Arm C: Interferon Beta-1a High Dose n=11 Participants Single dose of interferon beta-1a 30 µg IM Interferon beta-1a: Interferon beta-1a 30 µg administered IM	Arm D: Peginterferon Beta-1a Low Dose n=12 Participants Single dose of peginterferon beta-1a 31.25 µg subcutaneous (SC) Peginterferon beta-1a: Peginterferon beta-1a 31.25 µg administered SC	Arm E: Peginterferon Beta-1a Intermediate Dose n=12 Participants Single dose of peginterferon beta-1a 62.5 µg SC Peginterferon beta-1a: Peginterferon beta-1a 62.5 µg administered SC	Arm F: Peginterferon Beta-1a High Dose n=11 Participants Single dose of peginterferon beta-1a 125 µg SC Peginterferon beta-1a: Peginterferon beta-1a 125 µg administered SC
Maximum Concentration (Cmax) for Interferon Beta-1a and Peginterferon Beta-1a	39.5 pg/mL Geometric Coefficient of Variation 54	90.8 pg/mL Geometric Coefficient of Variation 66	143 pg/mL Geometric Coefficient of Variation 33	191 pg/mL Geometric Coefficient of Variation 49	434 pg/mL Geometric Coefficient of Variation 49	509 pg/mL Geometric Coefficient of Variation 65

SECONDARY outcome

Population: Analysis population includes all subjects who did not discontinue before the end of study.

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

Outcome measures

Outcome measures
Measure	Arm A: Interferon Beta-1a Low Dose n=12 Participants Single dose of interferon beta-1a 7.5 µg intramuscular (IM) Interferon beta-1a: Interferon beta-1a 7.5 µg administered IM	Arm B: Interferon Beta-1a Intermediate Dose n=12 Participants Single dose of interferon beta-1a 15 µg IM Interferon beta-1a: Interferon beta-1a 15 µg administered IM	Arm C: Interferon Beta-1a High Dose n=11 Participants Single dose of interferon beta-1a 30 µg IM Interferon beta-1a: Interferon beta-1a 30 µg administered IM	Arm D: Peginterferon Beta-1a Low Dose n=12 Participants Single dose of peginterferon beta-1a 31.25 µg subcutaneous (SC) Peginterferon beta-1a: Peginterferon beta-1a 31.25 µg administered SC	Arm E: Peginterferon Beta-1a Intermediate Dose n=12 Participants Single dose of peginterferon beta-1a 62.5 µg SC Peginterferon beta-1a: Peginterferon beta-1a 62.5 µg administered SC	Arm F: Peginterferon Beta-1a High Dose n=11 Participants Single dose of peginterferon beta-1a 125 µg SC Peginterferon beta-1a: Peginterferon beta-1a 125 µg administered SC
Area Under Effect Curve (AUEC) for Myxovirus-resistance Protein A (MxA) for Interferon Beta-1a and Peginterferon Beta-1a	140 ng*day/mL Standard Deviation 63	172 ng*day/mL Standard Deviation 92	211 ng*day/mL Standard Deviation 102	458 ng*day/mL Standard Deviation 303	732 ng*day/mL Standard Deviation 591	1137 ng*day/mL Standard Deviation 592

SECONDARY outcome

Population: Analysis population includes all subjects who did not discontinue before the end of study.

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

Outcome measures

Outcome measures
Measure	Arm A: Interferon Beta-1a Low Dose n=12 Participants Single dose of interferon beta-1a 7.5 µg intramuscular (IM) Interferon beta-1a: Interferon beta-1a 7.5 µg administered IM	Arm B: Interferon Beta-1a Intermediate Dose n=12 Participants Single dose of interferon beta-1a 15 µg IM Interferon beta-1a: Interferon beta-1a 15 µg administered IM	Arm C: Interferon Beta-1a High Dose n=11 Participants Single dose of interferon beta-1a 30 µg IM Interferon beta-1a: Interferon beta-1a 30 µg administered IM	Arm D: Peginterferon Beta-1a Low Dose n=12 Participants Single dose of peginterferon beta-1a 31.25 µg subcutaneous (SC) Peginterferon beta-1a: Peginterferon beta-1a 31.25 µg administered SC	Arm E: Peginterferon Beta-1a Intermediate Dose n=12 Participants Single dose of peginterferon beta-1a 62.5 µg SC Peginterferon beta-1a: Peginterferon beta-1a 62.5 µg administered SC	Arm F: Peginterferon Beta-1a High Dose n=11 Participants Single dose of peginterferon beta-1a 125 µg SC Peginterferon beta-1a: Peginterferon beta-1a 125 µg administered SC
Maximum Change From Baseline for Myxovirus-resistance Protein A (MxA) for Interferon Beta-1a and Peginterferon Beta-1a	52.9 ng/mL Standard Deviation 28.7	62.9 ng/mL Standard Deviation 31.7	73.4 ng/mL Standard Deviation 35.5	86.7 ng/mL Standard Deviation 49.0	117.6 ng/mL Standard Deviation 73.0	175.5 ng/mL Standard Deviation 93.5

SECONDARY outcome

Population: Analysis population for each group was limited to those subjects administered interferon beta-1a or placebo (interferon beta-1a group) or peginterferon beta-1a or placebo (peginterferon beta-1a group) who completed the study. One outlying result from peginterferon beta-1a high dose was excluded. Results from subjects administered placebo were used in all analyses. Confidence intervals for model parameters were generated using bootstrapping of the estimated model with 10000 repetitions.

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.

Outcome measures

Outcome measures
Measure	Arm A: Interferon Beta-1a Low Dose n=47 Participants Single dose of interferon beta-1a 7.5 µg intramuscular (IM) Interferon beta-1a: Interferon beta-1a 7.5 µg administered IM	Arm B: Interferon Beta-1a Intermediate Dose n=46 Participants Single dose of interferon beta-1a 15 µg IM Interferon beta-1a: Interferon beta-1a 15 µg administered IM	Arm C: Interferon Beta-1a High Dose Single dose of interferon beta-1a 30 µg IM Interferon beta-1a: Interferon beta-1a 30 µg administered IM	Arm D: Peginterferon Beta-1a Low Dose Single dose of peginterferon beta-1a 31.25 µg subcutaneous (SC) Peginterferon beta-1a: Peginterferon beta-1a 31.25 µg administered SC	Arm E: Peginterferon Beta-1a Intermediate Dose Single dose of peginterferon beta-1a 62.5 µg SC Peginterferon beta-1a: Peginterferon beta-1a 62.5 µg administered SC	Arm F: Peginterferon Beta-1a High Dose Single dose of peginterferon beta-1a 125 µg SC Peginterferon beta-1a: Peginterferon beta-1a 125 µg administered SC
Pharmacodynamic Model Parameter, Emax (Maximum Effect), for Neopterin Area Under the Effect Curve Models With Interferon Beta-1a or Peginterferon Beta-1a	13.3 ng/mL*day Interval 9.3 to 19.3	44.0 ng/mL*day Interval 28.8 to 59.7	—	—	—	—

SECONDARY outcome

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.

Outcome measures

Outcome measures
Measure	Arm A: Interferon Beta-1a Low Dose n=47 Participants Single dose of interferon beta-1a 7.5 µg intramuscular (IM) Interferon beta-1a: Interferon beta-1a 7.5 µg administered IM	Arm B: Interferon Beta-1a Intermediate Dose n=46 Participants Single dose of interferon beta-1a 15 µg IM Interferon beta-1a: Interferon beta-1a 15 µg administered IM	Arm C: Interferon Beta-1a High Dose Single dose of interferon beta-1a 30 µg IM Interferon beta-1a: Interferon beta-1a 30 µg administered IM	Arm D: Peginterferon Beta-1a Low Dose Single dose of peginterferon beta-1a 31.25 µg subcutaneous (SC) Peginterferon beta-1a: Peginterferon beta-1a 31.25 µg administered SC	Arm E: Peginterferon Beta-1a Intermediate Dose Single dose of peginterferon beta-1a 62.5 µg SC Peginterferon beta-1a: Peginterferon beta-1a 62.5 µg administered SC	Arm F: Peginterferon Beta-1a High Dose Single dose of peginterferon beta-1a 125 µg SC Peginterferon beta-1a: Peginterferon beta-1a 125 µg administered SC
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 ug Interval 0.3 to 15.1	84.1 ug Interval 30.8 to 422.0	—	—	—	—

SECONDARY outcome

Population: Analysis population for each group was limited to those subjects administered interferon beta-1a or placebo (the interferon beta-1a group) or administered peginterferon beta-1a or placebo (peginterferon beta-1a) who completed the study. Results from subjects administered placebo were used in all analyses. Confidence intervals for model parameters were generated using bootstrapping of the estimated model with 10000 repetitions.

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.

Outcome measures

Outcome measures
Measure	Arm A: Interferon Beta-1a Low Dose n=47 Participants Single dose of interferon beta-1a 7.5 µg intramuscular (IM) Interferon beta-1a: Interferon beta-1a 7.5 µg administered IM	Arm B: Interferon Beta-1a Intermediate Dose n=47 Participants Single dose of interferon beta-1a 15 µg IM Interferon beta-1a: Interferon beta-1a 15 µg administered IM	Arm C: Interferon Beta-1a High Dose Single dose of interferon beta-1a 30 µg IM Interferon beta-1a: Interferon beta-1a 30 µg administered IM	Arm D: Peginterferon Beta-1a Low Dose Single dose of peginterferon beta-1a 31.25 µg subcutaneous (SC) Peginterferon beta-1a: Peginterferon beta-1a 31.25 µg administered SC	Arm E: Peginterferon Beta-1a Intermediate Dose Single dose of peginterferon beta-1a 62.5 µg SC Peginterferon beta-1a: Peginterferon beta-1a 62.5 µg administered SC	Arm F: Peginterferon Beta-1a High Dose Single dose of peginterferon beta-1a 125 µg SC Peginterferon beta-1a: Peginterferon beta-1a 125 µg administered SC
Pharmacodynamic Model Parameter, Emax, for Neopterin Maximum Change From Baseline Models With Interferon Beta-1a or Peginterferon Beta-1a	5.7 ng/mL Interval 4.1 to 6.3	8.2 ng/mL Interval 5.7 to 12.4	—	—	—	—

SECONDARY outcome

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.