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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
494
Participants will receive subcutaneous (SC) injection of ustekinumab.
Participants will receive SC injection of ABP 654.
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
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
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
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
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.
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Burke Pharmaceutical Research
Hot Springs, Arkansas, United States
Zenith Research Inc.
Beverly Hills, California, United States
Center for Dermatology Clinical Research, Inc.
Fremont, California, United States
Quest Dermatology Research
Northridge, California, United States
Southern California Dermatology, Inc
Santa Ana, California, United States
Encore Research Group-Jacksonville Center for Clinical Resea
Jacksonville, Florida, United States
Altus Research, Inc.
Lake Worth, Florida, United States
International Dermatology Research, Inc.
Miami, Florida, United States
Leavitt Medical Associates of Florida d/b/a Ameriderm Research
Ormond Beach, Florida, United States
Riverchase Dermatology and Cosmetic Surgery
Pembroke Pines, Florida, United States
...and 78 more locations
Time frame: Baseline (day 1) and week 64
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
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
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
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
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