Psoriasis
Conditions
Keywords
Psoriasis, Biosimilar, Psoriasis area and severity index, Ustekinumab, Skin Diseases, Dermatologic Agents, Papulosquamous
Brief summary
The purpose of the study is to evaluate pharmacokinetic similarity, efficacy, safety and immunogenicity of multiple switches between ustekinumab and ABP 654 compared with continued use of ustekinumab in participants with moderate to severe plaque psoriasis.
Detailed description
This is a multi-center study and will enroll approximately 480 participants. After eligibility confirmation, all participants will be randomized in a 1:1 ratio into 2 treatment arms: continued use of ustekinumab or multiple switches between ustekinumab and ABP 654 at Week 28. The randomization will be stratified by prior biologic use for psoriasis (yes versus \[vs\] no) at baseline (Week 0), geographic region, and baseline (Week 0) body weight. All participants will receive an initial 3 doses of ustekinumab on Day 1 (Week 0), Week 4 and Week 16. At Week 28, participants will be randomized to continue on ustekinumab or switching between ABP 654 and ustekinumab every 12 weeks. At Week 28, efficacy assessments will be conducted including evaluation of Psoriasis and Area Severity Index (PASI). Participants who do not achieve PASI 50 response or better improvement at Week 28 will be considered as run-in failures and will not be randomized at Week 28; these participants will complete End of Study procedures at Week 28. The run-in period will occur from Day 1 until randomization at Week 28. Those unable to complete the Week 28 visit or did not have a PASI assessment completed at Week 28 will be discontinued from the study. The total duration of study participation for each participant will be 68 weeks, with up to 4 weeks for screening and 64 weeks after the first investigational product administration.
Interventions
DRUGUstekinumab
Participants will receive subcutaneous (SC) injection of ustekinumab.
DRUGABP 654
Participants will receive SC injection of ABP 654.
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
The investigators, study personnel (with the exception of the Data Monitoring Committee (DMC), and unblinded Parexel staff supporting DMC activities and randomization list activities) and the study participants will remain blinded to treatment allocation. ABP 654 and ustekinumab will be coded and labeled in a manner that protects blinding.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Participant has stable moderate to severe plaque psoriasis for at least 6 months * Participant has a score of PASI ≥ 12, involvement of ≥ 10% body surface area and static Physician Global Assessment ≥ 3 at screening and at baseline * Participant is a candidate for phototherapy or systemic therapy * Participant has previous failure, inadequate response, intolerance, or contraindication to at least 1 conventional antipsoriatic systemic therapy * Female participant should have a negative serum pregnancy test during screening and a negative urine pregnancy test at baseline * Participant or legally acceptable representative is capable of giving signed Institutional Review Board (IRB)/Independent Ethics Committee (IEC) informed consent * Participant has no known history of latent or active tuberculosis * Participant with a positive purified protein derivative (PPD) test and a history of Bacillus Calmette-Guérin (BCG) vaccination is allowed with a negative Quantiferon/T-spot test * Participant with a positive PPD test or participant with a positive or indeterminate Quantiferon/T-spot test is allowed if he/she has all the following: * No symptoms per tuberculosis worksheet provided by the sponsor, Amgen Inc. * Documented history of adequate prophylaxis initiation prior to receiving investigational product in accordance with local recommendations * No known exposure to a case of active tuberculosis after most recent prophylaxis * No evidence of active tuberculosis on chest radiograph within 3 months prior to the first dose of investigational product
Exclusion criteria
* Participant has erythrodermic psoriasis, pustular psoriasis, guttate psoriasis, medication induced psoriasis, or other skin conditions at the time of screening (eg, eczema) that would interfere with evaluations of the effect of investigational product of psoriasis * Participant has an active infection or history of infections * Participant has uncontrolled, clinically significant systemic disease, such as uncontrolled diabetes mellitus, cardiovascular disease, renal disease, liver disease, or hypertension * Participant has a mean QT internal or abnormal long QT syndrome corrected using Fridericia's formula (QTcF) of \> 450 msec (for male participant) or \> 470 msec (for female participant) at baseline that, in the opinion of the Investigator, is abnormal or clinically significant * Participant has moderate to severe heart failure (New York Heart Associate class III/IV) * Participant has known hypersensitivity to the investigational product or to any of the excipients * Participant has laboratory abnormalities at screening * Participant has had previous treatment with any agent specifically targeting interleukin (IL)-12 or IL-23 within 1 year prior to enrollment * Participant has received biologic treatment for psoriasis within the previous month or 5 drug half-lives (whichever is longer) prior to enrollment * Participant has received any investigational agents within the previous month or 5 half-lives (whichever is longer) prior to enrollment * Participant has received non-biologic systemic psoriasis therapy within 4 weeks prior to enrollment * Participant has received ultraviolet A phototherapy (with or without psoralen) or excimer laser within 4 weeks prior to enrollment, or ultraviolet B phototherapy within 2 weeks prior to enrollment * Participant has received topical psoriasis treatment within 2 weeks prior to enrollment * Participant has received other investigational procedures within 4 weeks prior to enrollment and during the course of the study * Female participant is pregnant or breastfeeding or planning to become pregnant while participating in the study and for at least 5 months after the last dose of investigational product * Sexually active participants and their partners who are of childbearing potential and not agreeing to use adequate protocol defined contraception methods while participating in the study and for 5 months after the last dose of investigational product
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration Time Curve (AUC) Over the Dosing Interval (AUCtau) Between Week 52 and Week 64 | Blood samples were taken pre-dose week 52; and at 2 days, 7 days, 10 days, 2 weeks, 4 weeks, 8 weeks, and 12 weeks after the week 52 dose | AUCtau from time 0 (week 52) over the dosing interval up to week 64 is presented. Pharmacokinetic (PK) parameters are based on ABP 654 in the switching group and on ustekinumab in the continued-use group. |
| Maximum Observed Serum Concentration (Cmax) Between Week 52 and Week 64 | Blood samples were taken pre-dose week 52; and at 2 days, 7 days, 10 days, 2 weeks, 4 weeks, 8 weeks, and 12 weeks after the week 52 dose | Cmax between week 52 and week 64 is presented. PK parameters are based on ABP 654 in the switching group and on ustekinumab in the continued-use group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PASI Percent Improvement From Baseline at Week 64 | Baseline (day 1) and week 64 | The PASI is a measure of the average redness (erythema), thickness (induration), and scaliness (scaling), each graded on a 0 to 4 scale of the lesions, weighted by the area of involvement. PASI combines the assessment of the severity of lesions and the area affected into a single score in the range 0 (no disease) to 72 (maximal disease). PASI percent improvement is defined as 100 x (value at baseline - value at post-baseline visit) / value at baseline. A positive value indicates PASI improvement. Baseline data were derived based on observed data and at week 64 were derived based on multiple imputation (MI) data. Baseline was defined as the last non-missing assessment taken prior to the first dose of investigational product for the study. |
| PASI 75 Response at Week 64 | Baseline (day 1) and week 64 | The PASI is a measure of the average redness (erythema), thickness (induration), and scaliness (scaling), each graded on a 0 to 4 scale of the lesions, weighted by the area of involvement. PASI combines the assessment of the severity of lesions and the area affected into a single score in the range 0 (no disease) to 72 (maximal disease). PASI response was defined as a participant meeting or surpassing a pre-specified threshold for percent improvement in PASI score compared to the baseline PASI score. An improvement of at least 75% qualified a participant as being a PASI 75 responder. Missing PASI 75 responses at week 64 were imputed by non-responder imputation (NRI). Baseline was defined as the last non-missing assessment taken prior to the first dose of investigational product for the study. |
| PASI 100 Response at Week 64 | Baseline (day 1) and week 64 | The PASI is a measure of the average redness (erythema), thickness (induration), and scaliness (scaling), each graded on a 0 to 4 scale of the lesions, weighted by the area of involvement. PASI combines the assessment of the severity of lesions and the area affected into a single score in the range 0 (no disease) to 72 (maximal disease). PASI response was defined as a participant meeting or surpassing a pre-specified threshold for percent improvement in PASI score compared to the baseline PASI score. An improvement of 100% qualified a participant as being a PASI 100 responder. Missing PASI 100 responses at week 64 were imputed by NRI. Baseline was defined as the last non-missing assessment taken prior to the first dose of investigational product for the study. |
| Time of Maximum Serum Concentration (Tmax) Between Week 52 and Week 64 | Blood samples were taken pre-dose week 52; and at 2 days, 7 days, 10 days, 2 weeks, 4 weeks, 8 weeks, and 12 weeks after the week 52 dose | Tmax between week 52 and week 64 is presented. PK parameters are based on ABP 654 in the switching group and on ustekinumab in the continued-use group. |
| Number of Participants With Events of Interest (EOI): Post-randomization Period | Week 28 to week 64 | The treatment-emergent EOIs prespecified for this study included serious systemic hypersensitivity reactions, facial palsy, pustular psoriasis, erythrodermic psoriasis, serious infections (including mycobacterial and salmonella infections), malignancy, cardiovascular events, reversible posterior leukoencephalopathy syndrome (RPLS), serious depression including suicidality, and venous thromboembolism. |
| Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Baseline (pre-dose day 1), week 4, week 16, week 28, week 40, week 52 and week 64 | The number of participants developing binding or neutralizing ADAs during the post-randomization period is defined as the number of participants in the safety analysis set who had a positive result post-randomization and had never tested positive (i.e., negative or no results) prior to the first dose of post-randomization investigational product and who have at least one ADA result post randomization. A transient antibody results was defined as a positive result during the post-randomization period with a negative result at the participant's last visit tested within the respective study period. Baseline was defined as the last non-missing assessment taken prior to the first dose of investigational product for the study. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs): Post-randomization Period | Week 28 to week 64 | TEAEs during the post-randomization period were defined as AEs that started on or after the first dose of investigational product post-randomization and prior to the end of study. The number of participants who experienced any TEAE, and who experienced a serious TEAE are presented. A serious TEAE was defined as any untoward medical occurrence that meets at least 1 of the following serious criteria: resulted in death (fatal), was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly/birth defect, or other medically important serious event. |
| Serum Trough Concentration at Steady-state (Ctrough,ss) at Week 28, Week 40, and Week 52 | Blood samples were taken pre-dose week 28, week 40, and week 52 | Ctrough,ss at weeks 28, 40, and 52 are presented. PK parameters are based on ABP 654 in the switching group and on ustekinumab in the continued-use group. |
Countries
Canada, Estonia, Georgia, Germany, Hungary, Latvia, Poland, United States
Participant flow
Recruitment details
Participants were enrolled at 87 study centers in 8 countries, including Canada, Estonia, Georgia, Germany, Hungary, Latvia, Poland, and the United States, and participated from 24 March 2021 to 28 February 2023.
Pre-assignment details
Participants with moderate to severe plaque psoriasis were randomized at week 28 to 1 of 2 treatment groups following a run-in period. Randomization was stratified by prior biologic use for psoriasis at baseline, geographic region, and body weight group at baseline. Dosage was weight-based to ensure similar concentration by body weight received.
Participants by arm
| Arm | Count |
|---|---|
| Post-randomization Switching: Ustekinumab RP and ABP 654 At week 28, eligible participants with a PASI 50 response or better were randomized to the switching group and received ABP 654 at week 28, ustekinumab RP at week 40, and ABP 654 at week 52. Ustekinumab RP and ABP 654 (45 mg \[baseline body weight ≤ 100 kg\] or 90 mg \[baseline body weight \> 100 kg\]) were administered by SC injection using a pre-filled syringe. | 228 |
| Post-randomization Continued-use: Ustekinumab RP At week 28, eligible participants with a PASI 50 response or better were randomized to the continued-use group to receive ustekinumab RP 45 mg (baseline body weight ≤ 100 kg) or 90 mg (baseline body weight \> 100 kg) at weeks 28, 40, and 52. Ustekinumab RP was administered by SC injection using a pre-filled syringe. | 225 |
| Total | 453 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Post-randomization Period | Adverse Event | 0 | 4 | 2 |
| Post-randomization Period | Family planning | 0 | 1 | 0 |
| Post-randomization Period | Lost to Follow-up | 0 | 6 | 6 |
| Post-randomization Period | Military service | 0 | 1 | 0 |
| Post-randomization Period | Pregnancy | 0 | 0 | 1 |
| Post-randomization Period | Study site closure | 0 | 0 | 1 |
| Post-randomization Period | Withdrawal by Subject | 0 | 7 | 6 |
| Run-in Period | Abnormal liver function | 1 | 0 | 0 |
| Run-in Period | Adverse Event | 6 | 0 | 0 |
| Run-in Period | Death | 1 | 0 | 0 |
| Run-in Period | Did not meet PASI 50 | 15 | 0 | 0 |
| Run-in Period | Lost to Follow-up | 2 | 0 | 0 |
| Run-in Period | Pregnancy | 2 | 0 | 0 |
| Run-in Period | Protocol Violation | 3 | 0 | 0 |
| Run-in Period | Required alternative therapy | 2 | 0 | 0 |
| Run-in Period | Study site closure | 2 | 0 | 0 |
| Run-in Period | Withdrawal by Subject | 7 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Post-randomization Switching: Ustekinumab RP and ABP 654 | Post-randomization Continued-use: Ustekinumab RP |
|---|---|---|---|
| Age, Continuous | 47.5 years STANDARD_DEVIATION 13.42 | 46.9 years STANDARD_DEVIATION 13.36 | 48.1 years STANDARD_DEVIATION 13.48 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 49 Participants | 26 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 403 Participants | 202 Participants | 201 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 3 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 12 Participants | 9 Participants | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 8 Participants | 7 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 3 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Not allowed to collect | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 5 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 421 Participants | 207 Participants | 214 Participants |
| Sex: Female, Male Female | 147 Participants | 64 Participants | 83 Participants |
| Sex: Female, Male Male | 306 Participants | 164 Participants | 142 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 | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 494 | 0 / 217 | 0 / 216 | 0 / 8 | 0 / 5 | 0 / 3 | 0 / 3 |
| other Total, other adverse events | 116 / 494 | 55 / 217 | 58 / 216 | 4 / 8 | 1 / 5 | 3 / 3 | 0 / 3 |
| serious Total, serious adverse events | 14 / 494 | 3 / 217 | 2 / 216 | 0 / 8 | 0 / 5 | 0 / 3 | 0 / 3 |
Outcome results
Primary
Area Under the Plasma Concentration Time Curve (AUC) Over the Dosing Interval (AUCtau) Between Week 52 and Week 64
AUCtau from time 0 (week 52) over the dosing interval up to week 64 is presented. Pharmacokinetic (PK) parameters are based on ABP 654 in the switching group and on ustekinumab in the continued-use group.
Time frame: Blood samples were taken pre-dose week 52; and at 2 days, 7 days, 10 days, 2 weeks, 4 weeks, 8 weeks, and 12 weeks after the week 52 dose
Population: The PK parameter analysis set consisted of all randomized participants who received all 3 doses of the assigned investigational product between week 28 and week 52 and who had an evaluable ABP 654 or ustekinumab serum concentration-time profile between week 52 and week 64. Participants with data available are presented.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Post-randomization Switching: Ustekinumab RP and ABP 654 | Area Under the Plasma Concentration Time Curve (AUC) Over the Dosing Interval (AUCtau) Between Week 52 and Week 64 | 5144.40 hour*mcg/mL | Geometric Coefficient of Variation 45.3 |
| Post-randomization Continued-use: Ustekinumab RP | Area Under the Plasma Concentration Time Curve (AUC) Over the Dosing Interval (AUCtau) Between Week 52 and Week 64 | 5768.45 hour*mcg/mL | Geometric Coefficient of Variation 50.4 |
Comparison: The ratio of geometric LS means, and 90% confidence intervals (CIs) were estimated using the analysis of covariance (ANCOVA) model adjusted for the actual stratification factors if prior biologic use for psoriasis, baseline body weight group, geographic region, and PK trough concentration at week 28.90% CI: [0.8874, 0.9799]
Primary
Maximum Observed Serum Concentration (Cmax) Between Week 52 and Week 64
Cmax between week 52 and week 64 is presented. PK parameters are based on ABP 654 in the switching group and on ustekinumab in the continued-use group.
Time frame: Blood samples were taken pre-dose week 52; and at 2 days, 7 days, 10 days, 2 weeks, 4 weeks, 8 weeks, and 12 weeks after the week 52 dose
Population: The PK parameter analysis set consisted of all randomized participants who received all 3 doses of the assigned investigational product between week 28 and week 52 and who had an evaluable ABP 654 or ustekinumab serum concentration-time profile between week 52 and week 64. Participants with data available are presented.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Post-randomization Switching: Ustekinumab RP and ABP 654 | Maximum Observed Serum Concentration (Cmax) Between Week 52 and Week 64 | 5.78 mcg/mL | Geometric Coefficient of Variation 41.4 |
| Post-randomization Continued-use: Ustekinumab RP | Maximum Observed Serum Concentration (Cmax) Between Week 52 and Week 64 | 6.31 mcg/mL | Geometric Coefficient of Variation 46.8 |
Comparison: The ratio of geometric LS means, and 90% CIs were estimated using the ANCOVA model adjusted for the actual stratification factors if prior biologic use for psoriasis, baseline body weight group, geographic region, and PK trough concentration at week 28.90% CI: [0.8977, 1.0018]
Secondary
Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period
The number of participants developing binding or neutralizing ADAs during the post-randomization period is defined as the number of participants in the safety analysis set who had a positive result post-randomization and had never tested positive (i.e., negative or no results) prior to the first dose of post-randomization investigational product and who have at least one ADA result post randomization. A transient antibody results was defined as a positive result during the post-randomization period with a negative result at the participant's last visit tested within the respective study period. Baseline was defined as the last non-missing assessment taken prior to the first dose of investigational product for the study.
Time frame: Baseline (pre-dose day 1), week 4, week 16, week 28, week 40, week 52 and week 64
Population: The safety analysis set included all randomized participants who received at least 1 dose of investigational product post randomization.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Post-randomization Switching: Ustekinumab RP and ABP 654 | Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Neutralizing antibody positive with negative/no result prior to first dose post-randomization | 8 Participants |
| Post-randomization Switching: Ustekinumab RP and ABP 654 | Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Neutralizing antibody negative/no result prior to first dose post-randomization | 190 Participants |
| Post-randomization Switching: Ustekinumab RP and ABP 654 | Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Binding antibody positive with negative/no result prior to first dose post-randomization | 7 Participants |
| Post-randomization Switching: Ustekinumab RP and ABP 654 | Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Participants with post-baseline result post-randomization | 217 Participants |
| Post-randomization Switching: Ustekinumab RP and ABP 654 | Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Transient neutralizing antibody positive with negative/no result prior first dose post-randomization | 6 Participants |
| Post-randomization Switching: Ustekinumab RP and ABP 654 | Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Transient binding antibody positive with negative/no result prior to first dose post-randomization | 4 Participants |
| Post-randomization Switching: Ustekinumab RP and ABP 654 | Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Binding antibody negative/no result prior to first dose post-randomization | 136 Participants |
| Post-randomization Continued-use: Ustekinumab RP | Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Neutralizing antibody positive with negative/no result prior to first dose post-randomization | 6 Participants |
| Post-randomization Continued-use: Ustekinumab RP | Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Neutralizing antibody negative/no result prior to first dose post-randomization | 188 Participants |
| Post-randomization Continued-use: Ustekinumab RP | Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Transient neutralizing antibody positive with negative/no result prior first dose post-randomization | 1 Participants |
| Post-randomization Continued-use: Ustekinumab RP | Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Participants with post-baseline result post-randomization | 216 Participants |
| Post-randomization Continued-use: Ustekinumab RP | Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Transient binding antibody positive with negative/no result prior to first dose post-randomization | 5 Participants |
| Post-randomization Continued-use: Ustekinumab RP | Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Binding antibody positive with negative/no result prior to first dose post-randomization | 11 Participants |
| Post-randomization Continued-use: Ustekinumab RP | Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Binding antibody negative/no result prior to first dose post-randomization | 134 Participants |
| Post-randomization Switching: ABP 654/Ustekinumab RP/Missing | Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Participants with post-baseline result post-randomization | 8 Participants |
| Post-randomization Switching: ABP 654/Ustekinumab RP/Missing | Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Binding antibody positive with negative/no result prior to first dose post-randomization | 0 Participants |
| Post-randomization Switching: ABP 654/Ustekinumab RP/Missing | Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Transient binding antibody positive with negative/no result prior to first dose post-randomization | 0 Participants |
| Post-randomization Switching: ABP 654/Ustekinumab RP/Missing | Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Neutralizing antibody negative/no result prior to first dose post-randomization | 6 Participants |
| Post-randomization Switching: ABP 654/Ustekinumab RP/Missing | Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Neutralizing antibody positive with negative/no result prior to first dose post-randomization | 0 Participants |
| Post-randomization Switching: ABP 654/Ustekinumab RP/Missing | Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Transient neutralizing antibody positive with negative/no result prior first dose post-randomization | 0 Participants |
| Post-randomization Switching: ABP 654/Ustekinumab RP/Missing | Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Binding antibody negative/no result prior to first dose post-randomization | 5 Participants |
| Post-randomization Continued-use: Ustekinumab RP/Ustekinumab RP/Missing | Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Binding antibody negative/no result prior to first dose post-randomization | 4 Participants |
| Post-randomization Continued-use: Ustekinumab RP/Ustekinumab RP/Missing | Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Neutralizing antibody negative/no result prior to first dose post-randomization | 5 Participants |
| Post-randomization Continued-use: Ustekinumab RP/Ustekinumab RP/Missing | Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Neutralizing antibody positive with negative/no result prior to first dose post-randomization | 1 Participants |
| Post-randomization Continued-use: Ustekinumab RP/Ustekinumab RP/Missing | Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Transient neutralizing antibody positive with negative/no result prior first dose post-randomization | 0 Participants |
| Post-randomization Continued-use: Ustekinumab RP/Ustekinumab RP/Missing | Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Transient binding antibody positive with negative/no result prior to first dose post-randomization | 0 Participants |
| Post-randomization Continued-use: Ustekinumab RP/Ustekinumab RP/Missing | Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Binding antibody positive with negative/no result prior to first dose post-randomization | 1 Participants |
| Post-randomization Continued-use: Ustekinumab RP/Ustekinumab RP/Missing | Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Participants with post-baseline result post-randomization | 5 Participants |
| Post-randomization Switching: ABP 654/Missing/Missing | Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Neutralizing antibody negative/no result prior to first dose post-randomization | 3 Participants |
| Post-randomization Switching: ABP 654/Missing/Missing | Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Transient binding antibody positive with negative/no result prior to first dose post-randomization | 0 Participants |
| Post-randomization Switching: ABP 654/Missing/Missing | Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Neutralizing antibody positive with negative/no result prior to first dose post-randomization | 0 Participants |
| Post-randomization Switching: ABP 654/Missing/Missing | Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Binding antibody positive with negative/no result prior to first dose post-randomization | 1 Participants |
| Post-randomization Switching: ABP 654/Missing/Missing | Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Binding antibody negative/no result prior to first dose post-randomization | 3 Participants |
| Post-randomization Switching: ABP 654/Missing/Missing | Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Transient neutralizing antibody positive with negative/no result prior first dose post-randomization | 0 Participants |
| Post-randomization Switching: ABP 654/Missing/Missing | Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Participants with post-baseline result post-randomization | 3 Participants |
| Post-randomization Continued-use: Ustekinumab RP/Missing/Missing | Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Binding antibody negative/no result prior to first dose post-randomization | 1 Participants |
| Post-randomization Continued-use: Ustekinumab RP/Missing/Missing | Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Binding antibody positive with negative/no result prior to first dose post-randomization | 0 Participants |
| Post-randomization Continued-use: Ustekinumab RP/Missing/Missing | Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Neutralizing antibody positive with negative/no result prior to first dose post-randomization | 0 Participants |
| Post-randomization Continued-use: Ustekinumab RP/Missing/Missing | Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Transient binding antibody positive with negative/no result prior to first dose post-randomization | 0 Participants |
| Post-randomization Continued-use: Ustekinumab RP/Missing/Missing | Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Neutralizing antibody negative/no result prior to first dose post-randomization | 1 Participants |
| Post-randomization Continued-use: Ustekinumab RP/Missing/Missing | Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Participants with post-baseline result post-randomization | 1 Participants |
| Post-randomization Continued-use: Ustekinumab RP/Missing/Missing | Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period | Transient neutralizing antibody positive with negative/no result prior first dose post-randomization | 0 Participants |
Secondary
Number of Participants With Events of Interest (EOI): Post-randomization Period
The treatment-emergent EOIs prespecified for this study included serious systemic hypersensitivity reactions, facial palsy, pustular psoriasis, erythrodermic psoriasis, serious infections (including mycobacterial and salmonella infections), malignancy, cardiovascular events, reversible posterior leukoencephalopathy syndrome (RPLS), serious depression including suicidality, and venous thromboembolism.
Time frame: Week 28 to week 64
Population: Participants in the safety analysis set who completed all planned doses of investigational product in the post-randomization period up to week 52. The safety analysis set included all randomized participants who received at least 1 dose of investigational product post randomization.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Post-randomization Switching: Ustekinumab RP and ABP 654 | Number of Participants With Events of Interest (EOI): Post-randomization Period | Facial palsy | 0 Participants |
| Post-randomization Switching: Ustekinumab RP and ABP 654 | Number of Participants With Events of Interest (EOI): Post-randomization Period | Any EOI | 6 Participants |
| Post-randomization Switching: Ustekinumab RP and ABP 654 | Number of Participants With Events of Interest (EOI): Post-randomization Period | Cardiovascular events | 2 Participants |
| Post-randomization Switching: Ustekinumab RP and ABP 654 | Number of Participants With Events of Interest (EOI): Post-randomization Period | RPLS | 2 Participants |
| Post-randomization Switching: Ustekinumab RP and ABP 654 | Number of Participants With Events of Interest (EOI): Post-randomization Period | Serious infections | 1 Participants |
| Post-randomization Switching: Ustekinumab RP and ABP 654 | Number of Participants With Events of Interest (EOI): Post-randomization Period | Malignancy | 1 Participants |
| Post-randomization Switching: Ustekinumab RP and ABP 654 | Number of Participants With Events of Interest (EOI): Post-randomization Period | Serious depression | 0 Participants |
| Post-randomization Switching: Ustekinumab RP and ABP 654 | Number of Participants With Events of Interest (EOI): Post-randomization Period | Serious systemic hypersensitivity reactions | 0 Participants |
| Post-randomization Switching: Ustekinumab RP and ABP 654 | Number of Participants With Events of Interest (EOI): Post-randomization Period | Pustular psoriasis | 0 Participants |
| Post-randomization Switching: Ustekinumab RP and ABP 654 | Number of Participants With Events of Interest (EOI): Post-randomization Period | Erythrodermic psoriasis | 0 Participants |
| Post-randomization Switching: Ustekinumab RP and ABP 654 | Number of Participants With Events of Interest (EOI): Post-randomization Period | Venous thromboembolism | 0 Participants |
| Post-randomization Continued-use: Ustekinumab RP | Number of Participants With Events of Interest (EOI): Post-randomization Period | Pustular psoriasis | 0 Participants |
| Post-randomization Continued-use: Ustekinumab RP | Number of Participants With Events of Interest (EOI): Post-randomization Period | Serious depression | 1 Participants |
| Post-randomization Continued-use: Ustekinumab RP | Number of Participants With Events of Interest (EOI): Post-randomization Period | Any EOI | 7 Participants |
| Post-randomization Continued-use: Ustekinumab RP | Number of Participants With Events of Interest (EOI): Post-randomization Period | Venous thromboembolism | 0 Participants |
| Post-randomization Continued-use: Ustekinumab RP | Number of Participants With Events of Interest (EOI): Post-randomization Period | Cardiovascular events | 3 Participants |
| Post-randomization Continued-use: Ustekinumab RP | Number of Participants With Events of Interest (EOI): Post-randomization Period | Serious systemic hypersensitivity reactions | 0 Participants |
| Post-randomization Continued-use: Ustekinumab RP | Number of Participants With Events of Interest (EOI): Post-randomization Period | RPLS | 0 Participants |
| Post-randomization Continued-use: Ustekinumab RP | Number of Participants With Events of Interest (EOI): Post-randomization Period | Facial palsy | 0 Participants |
| Post-randomization Continued-use: Ustekinumab RP | Number of Participants With Events of Interest (EOI): Post-randomization Period | Serious infections | 2 Participants |
| Post-randomization Continued-use: Ustekinumab RP | Number of Participants With Events of Interest (EOI): Post-randomization Period | Erythrodermic psoriasis | 0 Participants |
| Post-randomization Continued-use: Ustekinumab RP | Number of Participants With Events of Interest (EOI): Post-randomization Period | Malignancy | 1 Participants |
Comparison: Risk difference for any EOI: risk difference and CIs were estimated by Wald asymptotic confidence limits, or exact confidence limits if n \< 25 for either treatment.90% CI: [-4.17, 3.1]
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs): Post-randomization Period
TEAEs during the post-randomization period were defined as AEs that started on or after the first dose of investigational product post-randomization and prior to the end of study. The number of participants who experienced any TEAE, and who experienced a serious TEAE are presented. A serious TEAE was defined as any untoward medical occurrence that meets at least 1 of the following serious criteria: resulted in death (fatal), was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly/birth defect, or other medically important serious event.
Time frame: Week 28 to week 64
Population: The safety analysis set included all randomized participants who received at least 1 dose of investigational product post randomization.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Post-randomization Switching: Ustekinumab RP and ABP 654 | Number of Participants With Treatment-emergent Adverse Events (TEAEs): Post-randomization Period | Any TEAE | 97 Participants |
| Post-randomization Switching: Ustekinumab RP and ABP 654 | Number of Participants With Treatment-emergent Adverse Events (TEAEs): Post-randomization Period | Any serious TEAE | 3 Participants |
| Post-randomization Continued-use: Ustekinumab RP | Number of Participants With Treatment-emergent Adverse Events (TEAEs): Post-randomization Period | Any TEAE | 108 Participants |
| Post-randomization Continued-use: Ustekinumab RP | Number of Participants With Treatment-emergent Adverse Events (TEAEs): Post-randomization Period | Any serious TEAE | 2 Participants |
| Post-randomization Switching: ABP 654/Ustekinumab RP/Missing | Number of Participants With Treatment-emergent Adverse Events (TEAEs): Post-randomization Period | Any TEAE | 4 Participants |
| Post-randomization Switching: ABP 654/Ustekinumab RP/Missing | Number of Participants With Treatment-emergent Adverse Events (TEAEs): Post-randomization Period | Any serious TEAE | 0 Participants |
| Post-randomization Continued-use: Ustekinumab RP/Ustekinumab RP/Missing | Number of Participants With Treatment-emergent Adverse Events (TEAEs): Post-randomization Period | Any TEAE | 1 Participants |
| Post-randomization Continued-use: Ustekinumab RP/Ustekinumab RP/Missing | Number of Participants With Treatment-emergent Adverse Events (TEAEs): Post-randomization Period | Any serious TEAE | 0 Participants |
| Post-randomization Switching: ABP 654/Missing/Missing | Number of Participants With Treatment-emergent Adverse Events (TEAEs): Post-randomization Period | Any TEAE | 3 Participants |
| Post-randomization Switching: ABP 654/Missing/Missing | Number of Participants With Treatment-emergent Adverse Events (TEAEs): Post-randomization Period | Any serious TEAE | 0 Participants |
| Post-randomization Continued-use: Ustekinumab RP/Missing/Missing | Number of Participants With Treatment-emergent Adverse Events (TEAEs): Post-randomization Period | Any TEAE | 0 Participants |
| Post-randomization Continued-use: Ustekinumab RP/Missing/Missing | Number of Participants With Treatment-emergent Adverse Events (TEAEs): Post-randomization Period | Any serious TEAE | 0 Participants |
Secondary
PASI 100 Response at Week 64
The PASI is a measure of the average redness (erythema), thickness (induration), and scaliness (scaling), each graded on a 0 to 4 scale of the lesions, weighted by the area of involvement. PASI combines the assessment of the severity of lesions and the area affected into a single score in the range 0 (no disease) to 72 (maximal disease). PASI response was defined as a participant meeting or surpassing a pre-specified threshold for percent improvement in PASI score compared to the baseline PASI score. An improvement of 100% qualified a participant as being a PASI 100 responder. Missing PASI 100 responses at week 64 were imputed by NRI. Baseline was defined as the last non-missing assessment taken prior to the first dose of investigational product for the study.
Time frame: Baseline (day 1) and week 64
Population: The per-protocol efficacy analysis set included all participants who were randomized and received all 3 doses of the assigned interventional product between week 28 and week 52 and who did not experience an important protocol deviation during the study that could affect the evaluation of the efficacy endpoints. The overall number of participants analyzed includes those imputed by NRI as well as those with observed data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Post-randomization Switching: Ustekinumab RP and ABP 654 | PASI 100 Response at Week 64 | 36.1 Percentage of responders |
| Post-randomization Continued-use: Ustekinumab RP | PASI 100 Response at Week 64 | 35.8 Percentage of responders |
Comparison: Response difference was estimated by the Mantel-Haenszel estimate, and the 90% CIs were estimated by the stratified Newcombe confidence limits, adjusting for the prior biologic use of psoriasis, baseline body weight group, geographic region. Missing post-baseline binary response data were imputed by NRI.90% CI: [-7.4, 7.8]
Secondary
PASI 75 Response at Week 64
The PASI is a measure of the average redness (erythema), thickness (induration), and scaliness (scaling), each graded on a 0 to 4 scale of the lesions, weighted by the area of involvement. PASI combines the assessment of the severity of lesions and the area affected into a single score in the range 0 (no disease) to 72 (maximal disease). PASI response was defined as a participant meeting or surpassing a pre-specified threshold for percent improvement in PASI score compared to the baseline PASI score. An improvement of at least 75% qualified a participant as being a PASI 75 responder. Missing PASI 75 responses at week 64 were imputed by non-responder imputation (NRI). Baseline was defined as the last non-missing assessment taken prior to the first dose of investigational product for the study.
Time frame: Baseline (day 1) and week 64
Population: The per-protocol efficacy analysis set included all participants who were randomized and received all 3 doses of the assigned interventional product between week 28 and week 52 and who did not experience an important protocol deviation during the study that could affect the evaluation of the efficacy endpoints. The overall number of participants analyzed includes those imputed by NRI as well as those with observed data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Post-randomization Switching: Ustekinumab RP and ABP 654 | PASI 75 Response at Week 64 | 83.3 Percentage of responders |
| Post-randomization Continued-use: Ustekinumab RP | PASI 75 Response at Week 64 | 82.8 Percentage of responders |
Comparison: Response difference was estimated by the Mantel-Haenszel estimate, and the 90% CIs were estimated by the stratified Newcombe confidence limits, adjusting for the prior biologic use of psoriasis, baseline body weight group, geographic region. Missing post-baseline binary response data were imputed by NRI.90% CI: [-5.7, 6.2]
Secondary
PASI Percent Improvement From Baseline at Week 64
The PASI is a measure of the average redness (erythema), thickness (induration), and scaliness (scaling), each graded on a 0 to 4 scale of the lesions, weighted by the area of involvement. PASI combines the assessment of the severity of lesions and the area affected into a single score in the range 0 (no disease) to 72 (maximal disease). PASI percent improvement is defined as 100 x (value at baseline - value at post-baseline visit) / value at baseline. A positive value indicates PASI improvement. Baseline data were derived based on observed data and at week 64 were derived based on multiple imputation (MI) data. Baseline was defined as the last non-missing assessment taken prior to the first dose of investigational product for the study.
Time frame: Baseline (day 1) and week 64
Population: The per-protocol efficacy analysis set included all participants who were randomized and received all 3 doses of the assigned interventional product between week 28 and week 52 and who did not experience an important protocol deviation during the study that could affect the evaluation of the efficacy endpoints. The overall number of participants analyzed includes those imputed by MI as well as those with observed data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Post-randomization Switching: Ustekinumab RP and ABP 654 | PASI Percent Improvement From Baseline at Week 64 | 88.80 Percentage change | Standard Deviation 18.066 |
| Post-randomization Continued-use: Ustekinumab RP | PASI Percent Improvement From Baseline at Week 64 | 88.72 Percentage change | Standard Deviation 16.128 |
Comparison: Multiple imputation was applied for the point estimate and CI of the mean difference between the switching and continued-use groups. Missing PASI scores at the week 64 visit were imputed by MI.90% CI: [-2.62, 2.77]
Secondary
Serum Trough Concentration at Steady-state (Ctrough,ss) at Week 28, Week 40, and Week 52
Ctrough,ss at weeks 28, 40, and 52 are presented. PK parameters are based on ABP 654 in the switching group and on ustekinumab in the continued-use group.
Time frame: Blood samples were taken pre-dose week 28, week 40, and week 52
Population: The PK parameter analysis set consisted of all randomized participants who received all 3 doses of the assigned investigational product between week 28 and week 52 and who had an evaluable ABP 654 or ustekinumab serum concentration-time profile between week 52 and week 64. Participants with data available at each time point are presented and all participants in the overall number of participants analyzed contributed to the data in the endpoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Post-randomization Switching: Ustekinumab RP and ABP 654 | Serum Trough Concentration at Steady-state (Ctrough,ss) at Week 28, Week 40, and Week 52 | Week 40 | 537.52 ng/mL | Geometric Coefficient of Variation 96.4 |
| Post-randomization Switching: Ustekinumab RP and ABP 654 | Serum Trough Concentration at Steady-state (Ctrough,ss) at Week 28, Week 40, and Week 52 | Week 52 | 562.51 ng/mL | Geometric Coefficient of Variation 114 |
| Post-randomization Switching: Ustekinumab RP and ABP 654 | Serum Trough Concentration at Steady-state (Ctrough,ss) at Week 28, Week 40, and Week 52 | Week 28 | 570.46 ng/mL | Geometric Coefficient of Variation 105.9 |
| Post-randomization Continued-use: Ustekinumab RP | Serum Trough Concentration at Steady-state (Ctrough,ss) at Week 28, Week 40, and Week 52 | Week 28 | 595.86 ng/mL | Geometric Coefficient of Variation 110 |
| Post-randomization Continued-use: Ustekinumab RP | Serum Trough Concentration at Steady-state (Ctrough,ss) at Week 28, Week 40, and Week 52 | Week 40 | 590.61 ng/mL | Geometric Coefficient of Variation 103.9 |
| Post-randomization Continued-use: Ustekinumab RP | Serum Trough Concentration at Steady-state (Ctrough,ss) at Week 28, Week 40, and Week 52 | Week 52 | 599.11 ng/mL | Geometric Coefficient of Variation 108.5 |
Comparison: The ratio of Geometric LS means, and 90% CI for Ctrough,ss at week 28 were estimated based on an ANCOVA model adjusted for the actual stratification factors of prior biologic use for psoriasis, baseline body weight group, and geographic region.90% CI: [0.8319, 1.1119]
Comparison: The ratio of geometric LS means, and 90% CI for Ctrough,ss at week 40 between the 2 treatment groups were estimated using an ANCOVA model adjusting for stratification factors and PK trough concentration at week 28.90% CI: [0.8879, 1.0515]
Comparison: The ratio of geometric LS means, and 90% CI for Ctrough,ss at week 52 between the 2 treatment groups were estimated using an ANCOVA model adjusting for stratification factors and PK trough concentration at week 28.90% CI: [0.8916, 1.0785]
Secondary
Time of Maximum Serum Concentration (Tmax) Between Week 52 and Week 64
Tmax between week 52 and week 64 is presented. PK parameters are based on ABP 654 in the switching group and on ustekinumab in the continued-use group.
Time frame: Blood samples were taken pre-dose week 52; and at 2 days, 7 days, 10 days, 2 weeks, 4 weeks, 8 weeks, and 12 weeks after the week 52 dose
Population: The PK parameter analysis set consisted of all randomized participants who received all 3 doses of the assigned investigational product between week 28 and week 52 and who had an evaluable ABP 654 or ustekinumab serum concentration-time profile between week 52 and week 64. Participants with data available are presented.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Post-randomization Switching: Ustekinumab RP and ABP 654 | Time of Maximum Serum Concentration (Tmax) Between Week 52 and Week 64 | 167.80 hours |
| Post-randomization Continued-use: Ustekinumab RP | Time of Maximum Serum Concentration (Tmax) Between Week 52 and Week 64 | 168.93 hours |