Rheumatoid Arthritis
Conditions
Brief summary
A study to evaluate safety and tolerability and characterize the pharmacokinetic (PK) profile of rozibafusp alfa following multiple dose administration in adults with rheumatoid arthritis (RA).
Interventions
DRUGRozibafusp Alfa
Administered by subcutaneous injection once every 2 weeks.
DRUGPlacebo
Administered by subcutaneous injection once every 2 weeks.
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Body Mass Index: 18-35 kg/m\^2 * Diagnosed with RA (disease duration of at least 6 months) * Stable dose of methotrexate (5-25 mg weekly for ≥ 4 weeks) * Immunizations up to date * Willing to use highly effective contraception during treatment and through end-of-study
Exclusion criteria
* Uncontrolled, clinically significant systemic disease other than RA (i.e., diabetes mellitus, liver disease, asthma, cardiovascular disease, hypertension) * Malignancy within 5 years * Presence of serious infection, recurrent/chronic infections * Class IV RA according to American College of Rheumatology/ (ACR) revised response criteria * Diagnosed with Felty's syndrome * Known or suspected sensitivity to mammalian cell-derived products * History of alcohol and/or substance abuse within the last 12 months * Receipt of rituximab at any time in the past * Evidence of renal disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events | From first dose of study drug to 24 weeks after last dose (up to 34 weeks). | An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial subject, including worsening of a pre-existing medical condition and clinically significant changes in laboratory test results and physical exam findings. The event does not necessarily have a causal relationship with study treatment. AEs were graded for severity according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4, where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe or medically significant, Grade 4 = Life-threatening, and Grade 5 = Death. A serious adverse event is defined as an AE that met at least 1 of the following serious criteria: * fatal; * life threatening; * required in patient hospitalization or prolongation of existing hospitalization; * resulted in persistent or significant disability/incapacity; * congenital anomaly/birth defect; * other medically important serious event. The investigator assessed whether each AE was related to study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Serum Concentration (Cmax) of Rozibafusp Alfa | Day 1 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours post-dose. Week 10 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours and at 3, 4, 5, 6, 8, 10, and 12 weeks post-dose. | — |
| Area Under the Concentration-time Curve From 0 to 14 Days Postdose (AUC0-tau) for Rozibafusp Alfa | Day 1 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours post-dose. Week 10 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours post-dose. | — |
| Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) for Rozibafusp Alfa | Week 10 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours and at 3, 4, 5, 6, 8, 10, and 12 weeks post-dose. | — |
| Time to Maximum Observed Concentration (Tmax) of Rozibafusp Alfa | Day 1 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours post-dose. Week 10 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours and at 3, 4, 5, 6, 8, 10, and 12 weeks post-dose. | — |
| Accumulation Ratio of AUCtau | Day 1 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours post-dose. Week 10 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours post-dose | Accumulation ratio is the ratio of AUCtau after the last dosing interval (week 10) divided by AUCtau after the first dosing interval (day 1). |
| Accumulation Ratio of Cmax | Day 1 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours post-dose. Week 10 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours post-dose | Accumulation ratio is the ratio of Cmax after the last dosing interval (week 10) divided by Cmax after the first dosing interval (day 1). |
| Terminal Half-life of Rozibafusp Alfa | Week 10 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours and at 3, 4, 5, 6, 8, 10, and 12 weeks post-dose. | — |
Countries
Germany, United States
Participant flow
Recruitment details
This study was conducted at 4 centers in the United States and Germany. Participants with rheumatoid arthritis were enrolled from 14 August 2017 to 20 February 2019.
Pre-assignment details
The study consisted of 4 multiple ascending dose cohorts. Within each cohort participants were randomized in a 3:1 ratio to receive rozibafusp alfa or placebo. Escalation to a higher dose cohort was contingent on a review to confirm that the previous dose regimen(s) demonstrated an acceptable safety and tolerability profile.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo administered by subcutaneous injection once every 2 weeks for 10 weeks (6 doses). | 8 |
| Rozibafusp Alfa 70 mg Participants received 70 mg rozibafusp alfa administered by subcutaneous injection once every 2 weeks for 10 weeks (6 doses). | 7 |
| Rozibafusp Alfa 140 mg Participants received 140 mg rozibafusp alfa administered by subcutaneous injection once every 2 weeks for 10 weeks (6 doses). | 6 |
| Rozibafusp Alfa 210 mg Participants received 210 mg rozibafusp alfa administered by subcutaneous injection once every 2 weeks for 10 weeks (6 doses). | 6 |
| Rozibafusp Alfa 420 mg Participants received 420 mg rozibafusp alfa administered by subcutaneous injection once every 2 weeks for 10 weeks (6 doses). | 7 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 2 | 1 | 1 |
Baseline characteristics
| Characteristic | Rozibafusp Alfa 70 mg | Rozibafusp Alfa 140 mg | Rozibafusp Alfa 210 mg | Rozibafusp Alfa 420 mg | Total | Placebo |
|---|---|---|---|---|---|---|
| Age, Continuous | 60.4 years STANDARD_DEVIATION 11.9 | 61.0 years STANDARD_DEVIATION 11.2 | 60.7 years STANDARD_DEVIATION 9.6 | 58.7 years STANDARD_DEVIATION 4.9 | 60.2 years STANDARD_DEVIATION 9.2 | 55.1 years STANDARD_DEVIATION 8.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 6 Participants | 5 Participants | 6 Participants | 32 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 5 Participants | 6 Participants | 7 Participants | 32 Participants | 7 Participants |
| Sex: Female, Male Female | 7 Participants | 4 Participants | 6 Participants | 5 Participants | 28 Participants | 6 Participants |
| Sex: Female, Male Male | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 6 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 7 | 0 / 6 | 0 / 6 | 0 / 7 |
| other Total, other adverse events | 7 / 8 | 6 / 7 | 6 / 6 | 6 / 6 | 7 / 7 |
| serious Total, serious adverse events | 0 / 8 | 1 / 7 | 1 / 6 | 0 / 6 | 0 / 7 |
Outcome results
Primary
Number of Participants With Treatment-emergent Adverse Events
An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial subject, including worsening of a pre-existing medical condition and clinically significant changes in laboratory test results and physical exam findings. The event does not necessarily have a causal relationship with study treatment. AEs were graded for severity according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4, where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe or medically significant, Grade 4 = Life-threatening, and Grade 5 = Death. A serious adverse event is defined as an AE that met at least 1 of the following serious criteria: * fatal; * life threatening; * required in patient hospitalization or prolongation of existing hospitalization; * resulted in persistent or significant disability/incapacity; * congenital anomaly/birth defect; * other medically important serious event. The investigator assessed whether each AE was related to study drug.
Time frame: From first dose of study drug to 24 weeks after last dose (up to 34 weeks).
Population: All randomized participants who received at least 1 dose of rozibafusp alfa or placebo.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-emergent Adverse Events | Life-threatening adverse events | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events | TRAE Grade ≥ 2 | 2 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events | Fatal adverse events | 0.0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events | Any treatment-emergent adverse event (TEAE) | 7 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events | Treatment-related TEAE (TRAE) | 2 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events | Life-threatening TRAE | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 4 | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 3 | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events | Severe TRAE | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events | TRAE leading to discontinuation of study drug | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events | Serious adverse events | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events | Fatal TRAE | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events | Treatment-related serious adverse events | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation of study drug | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events | TRAE Grade ≥ 4 | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events | Severe adverse events | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 2 | 4 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events | TRAE Grade ≥ 3 | 0 Participants |
| Rozibafusp Alfa 70 mg | Number of Participants With Treatment-emergent Adverse Events | Fatal TRAE | 0 Participants |
| Rozibafusp Alfa 70 mg | Number of Participants With Treatment-emergent Adverse Events | Life-threatening adverse events | 0 Participants |
| Rozibafusp Alfa 70 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 2 | 5 Participants |
| Rozibafusp Alfa 70 mg | Number of Participants With Treatment-emergent Adverse Events | TRAE Grade ≥ 2 | 0 Participants |
| Rozibafusp Alfa 70 mg | Number of Participants With Treatment-emergent Adverse Events | TRAE leading to discontinuation of study drug | 0 Participants |
| Rozibafusp Alfa 70 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation of study drug | 0 Participants |
| Rozibafusp Alfa 70 mg | Number of Participants With Treatment-emergent Adverse Events | Fatal adverse events | 0 Participants |
| Rozibafusp Alfa 70 mg | Number of Participants With Treatment-emergent Adverse Events | Life-threatening TRAE | 0 Participants |
| Rozibafusp Alfa 70 mg | Number of Participants With Treatment-emergent Adverse Events | Treatment-related TEAE (TRAE) | 0 Participants |
| Rozibafusp Alfa 70 mg | Number of Participants With Treatment-emergent Adverse Events | Serious adverse events | 1 Participants |
| Rozibafusp Alfa 70 mg | Number of Participants With Treatment-emergent Adverse Events | TRAE Grade ≥ 4 | 0 Participants |
| Rozibafusp Alfa 70 mg | Number of Participants With Treatment-emergent Adverse Events | Treatment-related serious adverse events | 0 Participants |
| Rozibafusp Alfa 70 mg | Number of Participants With Treatment-emergent Adverse Events | Severe adverse events | 1 Participants |
| Rozibafusp Alfa 70 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 3 | 1 Participants |
| Rozibafusp Alfa 70 mg | Number of Participants With Treatment-emergent Adverse Events | Any treatment-emergent adverse event (TEAE) | 6 Participants |
| Rozibafusp Alfa 70 mg | Number of Participants With Treatment-emergent Adverse Events | Severe TRAE | 0 Participants |
| Rozibafusp Alfa 70 mg | Number of Participants With Treatment-emergent Adverse Events | TRAE Grade ≥ 3 | 0 Participants |
| Rozibafusp Alfa 70 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 4 | 0 Participants |
| Rozibafusp Alfa 140 mg | Number of Participants With Treatment-emergent Adverse Events | Severe TRAE | 0 Participants |
| Rozibafusp Alfa 140 mg | Number of Participants With Treatment-emergent Adverse Events | Any treatment-emergent adverse event (TEAE) | 6 Participants |
| Rozibafusp Alfa 140 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 2 | 3 Participants |
| Rozibafusp Alfa 140 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 3 | 1 Participants |
| Rozibafusp Alfa 140 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 4 | 0 Participants |
| Rozibafusp Alfa 140 mg | Number of Participants With Treatment-emergent Adverse Events | Serious adverse events | 1 Participants |
| Rozibafusp Alfa 140 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation of study drug | 0 Participants |
| Rozibafusp Alfa 140 mg | Number of Participants With Treatment-emergent Adverse Events | Severe adverse events | 1 Participants |
| Rozibafusp Alfa 140 mg | Number of Participants With Treatment-emergent Adverse Events | Life-threatening adverse events | 0 Participants |
| Rozibafusp Alfa 140 mg | Number of Participants With Treatment-emergent Adverse Events | Fatal adverse events | 0 Participants |
| Rozibafusp Alfa 140 mg | Number of Participants With Treatment-emergent Adverse Events | Treatment-related TEAE (TRAE) | 1 Participants |
| Rozibafusp Alfa 140 mg | Number of Participants With Treatment-emergent Adverse Events | TRAE Grade ≥ 2 | 0 Participants |
| Rozibafusp Alfa 140 mg | Number of Participants With Treatment-emergent Adverse Events | TRAE Grade ≥ 3 | 0 Participants |
| Rozibafusp Alfa 140 mg | Number of Participants With Treatment-emergent Adverse Events | TRAE Grade ≥ 4 | 0 Participants |
| Rozibafusp Alfa 140 mg | Number of Participants With Treatment-emergent Adverse Events | Treatment-related serious adverse events | 0 Participants |
| Rozibafusp Alfa 140 mg | Number of Participants With Treatment-emergent Adverse Events | TRAE leading to discontinuation of study drug | 0 Participants |
| Rozibafusp Alfa 140 mg | Number of Participants With Treatment-emergent Adverse Events | Life-threatening TRAE | 0 Participants |
| Rozibafusp Alfa 140 mg | Number of Participants With Treatment-emergent Adverse Events | Fatal TRAE | 0 Participants |
| Rozibafusp Alfa 210 mg | Number of Participants With Treatment-emergent Adverse Events | Life-threatening TRAE | 0 Participants |
| Rozibafusp Alfa 210 mg | Number of Participants With Treatment-emergent Adverse Events | Severe adverse events | 0 Participants |
| Rozibafusp Alfa 210 mg | Number of Participants With Treatment-emergent Adverse Events | TRAE Grade ≥ 3 | 0 Participants |
| Rozibafusp Alfa 210 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation of study drug | 0 Participants |
| Rozibafusp Alfa 210 mg | Number of Participants With Treatment-emergent Adverse Events | Any treatment-emergent adverse event (TEAE) | 6 Participants |
| Rozibafusp Alfa 210 mg | Number of Participants With Treatment-emergent Adverse Events | TRAE Grade ≥ 4 | 0 Participants |
| Rozibafusp Alfa 210 mg | Number of Participants With Treatment-emergent Adverse Events | Serious adverse events | 0 Participants |
| Rozibafusp Alfa 210 mg | Number of Participants With Treatment-emergent Adverse Events | Severe TRAE | 0 Participants |
| Rozibafusp Alfa 210 mg | Number of Participants With Treatment-emergent Adverse Events | Treatment-related serious adverse events | 0 Participants |
| Rozibafusp Alfa 210 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 4 | 0 Participants |
| Rozibafusp Alfa 210 mg | Number of Participants With Treatment-emergent Adverse Events | TRAE leading to discontinuation of study drug | 0 Participants |
| Rozibafusp Alfa 210 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 3 | 0 Participants |
| Rozibafusp Alfa 210 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 2 | 4 Participants |
| Rozibafusp Alfa 210 mg | Number of Participants With Treatment-emergent Adverse Events | Fatal adverse events | 0 Participants |
| Rozibafusp Alfa 210 mg | Number of Participants With Treatment-emergent Adverse Events | Fatal TRAE | 0 Participants |
| Rozibafusp Alfa 210 mg | Number of Participants With Treatment-emergent Adverse Events | Treatment-related TEAE (TRAE) | 1 Participants |
| Rozibafusp Alfa 210 mg | Number of Participants With Treatment-emergent Adverse Events | Life-threatening adverse events | 0 Participants |
| Rozibafusp Alfa 210 mg | Number of Participants With Treatment-emergent Adverse Events | TRAE Grade ≥ 2 | 1 Participants |
| Rozibafusp Alfa 420 mg | Number of Participants With Treatment-emergent Adverse Events | Any treatment-emergent adverse event (TEAE) | 7 Participants |
| Rozibafusp Alfa 420 mg | Number of Participants With Treatment-emergent Adverse Events | TRAE Grade ≥ 2 | 2 Participants |
| Rozibafusp Alfa 420 mg | Number of Participants With Treatment-emergent Adverse Events | Severe adverse events | 0 Participants |
| Rozibafusp Alfa 420 mg | Number of Participants With Treatment-emergent Adverse Events | Fatal TRAE | 0 Participants |
| Rozibafusp Alfa 420 mg | Number of Participants With Treatment-emergent Adverse Events | Life-threatening TRAE | 0 Participants |
| Rozibafusp Alfa 420 mg | Number of Participants With Treatment-emergent Adverse Events | Fatal adverse events | 0 Participants |
| Rozibafusp Alfa 420 mg | Number of Participants With Treatment-emergent Adverse Events | TRAE Grade ≥ 3 | 0 Participants |
| Rozibafusp Alfa 420 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation of study drug | 0 Participants |
| Rozibafusp Alfa 420 mg | Number of Participants With Treatment-emergent Adverse Events | TRAE leading to discontinuation of study drug | 0 Participants |
| Rozibafusp Alfa 420 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 3 | 0 Participants |
| Rozibafusp Alfa 420 mg | Number of Participants With Treatment-emergent Adverse Events | Life-threatening adverse events | 0 Participants |
| Rozibafusp Alfa 420 mg | Number of Participants With Treatment-emergent Adverse Events | TRAE Grade ≥ 4 | 0 Participants |
| Rozibafusp Alfa 420 mg | Number of Participants With Treatment-emergent Adverse Events | Serious adverse events | 0 Participants |
| Rozibafusp Alfa 420 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 2 | 6 Participants |
| Rozibafusp Alfa 420 mg | Number of Participants With Treatment-emergent Adverse Events | Severe TRAE | 0 Participants |
| Rozibafusp Alfa 420 mg | Number of Participants With Treatment-emergent Adverse Events | Treatment-related TEAE (TRAE) | 4 Participants |
| Rozibafusp Alfa 420 mg | Number of Participants With Treatment-emergent Adverse Events | Treatment-related serious adverse events | 0 Participants |
| Rozibafusp Alfa 420 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 4 | 0 Participants |
Secondary
Accumulation Ratio of AUCtau
Accumulation ratio is the ratio of AUCtau after the last dosing interval (week 10) divided by AUCtau after the first dosing interval (day 1).
Time frame: Day 1 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours post-dose. Week 10 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours post-dose
Population: PK parameter analysis set with available AUCtau data at day 1 and week 10
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Accumulation Ratio of AUCtau | 2.94 ratio | Standard Deviation 1.75 |
| Rozibafusp Alfa 70 mg | Accumulation Ratio of AUCtau | 3.55 ratio | Standard Deviation 1.2 |
| Rozibafusp Alfa 140 mg | Accumulation Ratio of AUCtau | 4.41 ratio | Standard Deviation 2.28 |
| Rozibafusp Alfa 210 mg | Accumulation Ratio of AUCtau | 4.27 ratio | Standard Deviation 3.24 |
Secondary
Accumulation Ratio of Cmax
Accumulation ratio is the ratio of Cmax after the last dosing interval (week 10) divided by Cmax after the first dosing interval (day 1).
Time frame: Day 1 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours post-dose. Week 10 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours post-dose
Population: PK parameter analysis set with available Cmax data at day 1 and week 10
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Accumulation Ratio of Cmax | 3.08 ratio | Standard Deviation 1.96 |
| Rozibafusp Alfa 70 mg | Accumulation Ratio of Cmax | 3.00 ratio | Standard Deviation 1.05 |
| Rozibafusp Alfa 140 mg | Accumulation Ratio of Cmax | 4.06 ratio | Standard Deviation 2.12 |
| Rozibafusp Alfa 210 mg | Accumulation Ratio of Cmax | 3.71 ratio | Standard Deviation 2.38 |
Secondary
Area Under the Concentration-time Curve From 0 to 14 Days Postdose (AUC0-tau) for Rozibafusp Alfa
Time frame: Day 1 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours post-dose. Week 10 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours post-dose.
Population: PK parameter analysis set with available data at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Area Under the Concentration-time Curve From 0 to 14 Days Postdose (AUC0-tau) for Rozibafusp Alfa | Day 1 | 22.6 day*μg/mL | Standard Deviation 14.7 |
| Placebo | Area Under the Concentration-time Curve From 0 to 14 Days Postdose (AUC0-tau) for Rozibafusp Alfa | Week 10 | 57.1 day*μg/mL | Standard Deviation 33.6 |
| Rozibafusp Alfa 70 mg | Area Under the Concentration-time Curve From 0 to 14 Days Postdose (AUC0-tau) for Rozibafusp Alfa | Week 10 | 284 day*μg/mL | Standard Deviation 170 |
| Rozibafusp Alfa 70 mg | Area Under the Concentration-time Curve From 0 to 14 Days Postdose (AUC0-tau) for Rozibafusp Alfa | Day 1 | 86.2 day*μg/mL | Standard Deviation 47.1 |
| Rozibafusp Alfa 140 mg | Area Under the Concentration-time Curve From 0 to 14 Days Postdose (AUC0-tau) for Rozibafusp Alfa | Week 10 | 510 day*μg/mL | Standard Deviation 151 |
| Rozibafusp Alfa 140 mg | Area Under the Concentration-time Curve From 0 to 14 Days Postdose (AUC0-tau) for Rozibafusp Alfa | Day 1 | 143 day*μg/mL | Standard Deviation 85.3 |
| Rozibafusp Alfa 210 mg | Area Under the Concentration-time Curve From 0 to 14 Days Postdose (AUC0-tau) for Rozibafusp Alfa | Day 1 | 265 day*μg/mL | Standard Deviation 162 |
| Rozibafusp Alfa 210 mg | Area Under the Concentration-time Curve From 0 to 14 Days Postdose (AUC0-tau) for Rozibafusp Alfa | Week 10 | 864 day*μg/mL | Standard Deviation 206 |
Secondary
Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) for Rozibafusp Alfa
Time frame: Week 10 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours and at 3, 4, 5, 6, 8, 10, and 12 weeks post-dose.
Population: PK parameter analysis set with available data at each time point
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) for Rozibafusp Alfa | 107 day*μg/mL | Standard Deviation 82.4 |
| Rozibafusp Alfa 70 mg | Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) for Rozibafusp Alfa | 651 day*μg/mL | Standard Deviation 483 |
| Rozibafusp Alfa 140 mg | Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) for Rozibafusp Alfa | 1110 day*μg/mL | Standard Deviation 447 |
| Rozibafusp Alfa 210 mg | Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) for Rozibafusp Alfa | 2160 day*μg/mL | Standard Deviation 606 |
Secondary
Maximum Observed Serum Concentration (Cmax) of Rozibafusp Alfa
Time frame: Day 1 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours post-dose. Week 10 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours and at 3, 4, 5, 6, 8, 10, and 12 weeks post-dose.
Population: PK parameter analysis set with available data at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Maximum Observed Serum Concentration (Cmax) of Rozibafusp Alfa | Day 1 | 2.56 μg/mL | Standard Deviation 1.51 |
| Placebo | Maximum Observed Serum Concentration (Cmax) of Rozibafusp Alfa | Week 10 | 6.85 μg/mL | Standard Deviation 4.59 |
| Rozibafusp Alfa 70 mg | Maximum Observed Serum Concentration (Cmax) of Rozibafusp Alfa | Week 10 | 22.7 μg/mL | Standard Deviation 12.6 |
| Rozibafusp Alfa 70 mg | Maximum Observed Serum Concentration (Cmax) of Rozibafusp Alfa | Day 1 | 8.34 μg/mL | Standard Deviation 4.09 |
| Rozibafusp Alfa 140 mg | Maximum Observed Serum Concentration (Cmax) of Rozibafusp Alfa | Day 1 | 13.7 μg/mL | Standard Deviation 7.22 |
| Rozibafusp Alfa 140 mg | Maximum Observed Serum Concentration (Cmax) of Rozibafusp Alfa | Week 10 | 44.1 μg/mL | Standard Deviation 13.4 |
| Rozibafusp Alfa 210 mg | Maximum Observed Serum Concentration (Cmax) of Rozibafusp Alfa | Day 1 | 24.1 μg/mL | Standard Deviation 11.1 |
| Rozibafusp Alfa 210 mg | Maximum Observed Serum Concentration (Cmax) of Rozibafusp Alfa | Week 10 | 67.9 μg/mL | Standard Deviation 18.7 |
Secondary
Terminal Half-life of Rozibafusp Alfa
Time frame: Week 10 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours and at 3, 4, 5, 6, 8, 10, and 12 weeks post-dose.
Population: PK parameter analysis set with available data at each time point
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Terminal Half-life of Rozibafusp Alfa | 4.62 days | Standard Deviation 1.05 |
| Rozibafusp Alfa 70 mg | Terminal Half-life of Rozibafusp Alfa | 5.62 days | Standard Deviation 1.14 |
| Rozibafusp Alfa 140 mg | Terminal Half-life of Rozibafusp Alfa | 6.68 days | Standard Deviation 3.48 |
| Rozibafusp Alfa 210 mg | Terminal Half-life of Rozibafusp Alfa | 9.50 days | Standard Deviation 3.44 |
Secondary
Time to Maximum Observed Concentration (Tmax) of Rozibafusp Alfa
Time frame: Day 1 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours post-dose. Week 10 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours and at 3, 4, 5, 6, 8, 10, and 12 weeks post-dose.
Population: The pharmacokinetic (PK) parameter analysis set includes all randomized participants who received rozibafusp alfa and for whom PK parameters were adequately estimated.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Time to Maximum Observed Concentration (Tmax) of Rozibafusp Alfa | Day 1 | 3.0 days |
| Placebo | Time to Maximum Observed Concentration (Tmax) of Rozibafusp Alfa | Week 10 | 3.0 days |
| Rozibafusp Alfa 70 mg | Time to Maximum Observed Concentration (Tmax) of Rozibafusp Alfa | Week 10 | 5.0 days |
| Rozibafusp Alfa 70 mg | Time to Maximum Observed Concentration (Tmax) of Rozibafusp Alfa | Day 1 | 3.0 days |
| Rozibafusp Alfa 140 mg | Time to Maximum Observed Concentration (Tmax) of Rozibafusp Alfa | Day 1 | 4.5 days |
| Rozibafusp Alfa 140 mg | Time to Maximum Observed Concentration (Tmax) of Rozibafusp Alfa | Week 10 | 2.5 days |
| Rozibafusp Alfa 210 mg | Time to Maximum Observed Concentration (Tmax) of Rozibafusp Alfa | Day 1 | 6.0 days |
| Rozibafusp Alfa 210 mg | Time to Maximum Observed Concentration (Tmax) of Rozibafusp Alfa | Week 10 | 2.5 days |