Plaque Psoriasis
Conditions
Keywords
Psoriasis, Biosimilar, Psoriasis area and severity index
Brief summary
The purpose of the study is to evaluate the efficacy, safety, and immunogenicity of ABP 654 compared with ustekinumab in participants with moderate to severe plaque psoriasis.
Detailed description
This is a multicenter study and will enroll approximately 542 participants. The total duration of study participation for each participant will be 56 weeks, with up to 4 weeks for screening, and for 52 weeks after the first administration of either ABP 654 or ustekinumab. After confirmation of eligibility, all participants will be randomized in a 1:1 ratio into 2 treatment groups (Group A will receive ABP 654, and Group B will receive ustekinumab) stratified by prior biologic use for psoriasis (yes versus \[vs\] no), geographic region, and baseline body weight (BW). Based on the psoriasis area and severity index (PASI) score (to determine better improvement or partial improvement) at week 28, the participants in the study will proceed as follows: 1. Participants who do not achieve PASI 50 response or better improvement at Week 28 will be considered to have completed the study and will complete end of study procedures (ie, week 52 procedures), and those unable to complete week 28 visit, or did not have a PASI assessment completed, will be discontinued from the study. 2. Participants who achieve PASI 75 response or better improvement will continue on the study and will be re-randomized in a blinded fashion such that participants initially randomized to Group A (ABP 654) will continue to receive ABP 654 and those in Group B (ustekinumab) will re-randomized, to either continue on ustekinumab (Treatment Group B1) or switch to ABP 654 (Treatment Group B2). 3. Participants with PASI 50 response or better but less than PASI 75 response and on the Investigator's decision, participants will continue on the originally assigned treatment with dose intensification and will not be re-randomized. However, participants that do not dose intensify will be re-randomized.
Interventions
DRUGABP 654
Participants will receive SC injection of ABP 654.
DRUGUstekinumab
Participants will receive SC injection of ustekinumab.
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The Investigators, study personnel with the exception of the clinical research organization's unblinded biostatistician and unblinded programmers; and the data monitoring committee, and the study participants will remain blinded to treatment allocation.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Participants are eligible to be included in the study only if all of the following criteria apply: * Stable moderate to severe plaque psoriasis for at least 6 months * Baseline score of PASI \>= 12, involvement of \>= 10% BSA, and sPGA \>= 3 at screening and at baseline * Candidate for phototherapy or systemic therapy * Previous failure, inadequate response, intolerance, or contraindication to at least 1 conventional anti-psoriatic systemic therapy * Female participants should have negative serum pregnancy test during screening and a negative urine pregnancy test at baseline * No known history of latent or active tuberculosis (TB), and has a negative test for TB during screening (with negative purified protein derivative (PPD), and Negative Quantiferon®/T-spot test) * Participants with a positive purified protein derivative and a history of Bacillus Calmette-Guérin (BCG) vaccination are allowed with a negative Quantiferon®/T-spot® * Participants with a positive PPD test (without history of BCG vaccination) or participants with a positive or indeterminate Quantiferon®/T-spot test are allowed if they have all of the following: * No symptoms per TB worksheet provided by the sponsor * Documented history of adequate prophylaxis initiation prior to receiving investigational product (IP) in accordance with local recommendations * No known exposure to a case of active TB after most recent prophylaxis * No evidence of active TB on chest radiograph within 3 months prior to the first dose of IP
Exclusion criteria
Participants are excluded from the study if any of the following criteria apply: * Skin disease related conditions such as, Erythrodermic psoriasis (PsO), pustular PsO, guttate PsO, medication induced PsO, or other skin conditions at the time of the screening visit (eg, eczema) that would interfere with evaluations of the effect of IP on PsO * Participant has an active infection, recurrent or chronic infections, serious infection or history of infections * Known history of human immunodeficiency virus * Hepatitis B surface antigen or hepatitis C virus antibody positivity at screening * Uncontrolled, clinically significant systemic disease such as uncontrolled diabetes mellitus, cardiovascular disease, renal disease, liver disease, or hypertension * Moderate to severe heart failure (New York Heart Associate class III/IV) * Known hypersensitivity to the IP or to any of the excipients * Any abnormal laboratory parameters at screening, as defined in protocol * Previous treatment with any agent specifically targeting interleukin (IL)-12 or IL-23 * Received biologic treatment for psoriasis within the previous month or 5 drug half-lives prior to randomization * Received non-biologic systemic psoriasis therapy within 4 weeks prior to randomization * Received Ultra-violet A (UVA) phototherapy (with or without psoralen) or excimer laser within 4 weeks prior to randomization, or ultra-violet B (UVB) phototherapy within 2 weeks prior to randomization * Received topical psoriasis treatment within 2 weeks prior to randomization (exception: upper mid-strength to least potent \[class III to VII\] topical steroids permitted on the palms, soles, face, and intertriginous areas; bland emollients) * Received live viral or live bacterial vaccination within 2 weeks prior to randomization * Received BCG vaccination within 1 year prior to randomization * Other investigational procedures within 4 weeks prior to randomization and during the study * Participants not agreeing to follow protocol defined contraceptives procedures * Participants likely not to be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PASI Percent Change From Baseline to Week 12 | Baseline (Day 1 [Week 0]) and Week 12 | The PASI is a measure of the average redness (erythema), thickness (induration), and scaliness (scaling; each graded on a 0-4 scale \[0 = clear; 1-4 = increasing severity\]) of the lesions, weighted by the area of involvement in the four main body areas (i.e., head, arms, trunk to groin, and legs to top of buttocks). The PASI score ranges from 0 to 72. Higher scores represent worse symptom severity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With PASI 75 Response Throughout the Study | Baseline (Day 1 [Week 0]), Weeks 4, 16, 28, 36 (dose intensification only), 40 (re-randomized FAS only), 44 (dose intensification only) and Week 52 (EOS) | Reduction in disease was measured by PASI score. The PASI 75 response is a 75% or greater improvement (reduction in disease \[PASI 75\]) from baseline in PASI score. The PASI is a measure of the average redness (erythema), thickness (induration), and scaliness (scaling; each graded on a 0-4 scale \[0 = clear; 1-4 = increasing severity\]) of the lesions, weighted by the area of involvement in the four main body areas (i.e., head, arms, trunk to groin, and legs to top of buttocks). The PASI score ranges from 0 to 72. Higher scores represent worse symptom severity. |
| Percentage of Participants With PASI 100 Response Throughout the Study | Baseline (Day 1 [Week 0]), Weeks 4, 16, 28, 36 (dose intensification only), 40 (re-randomized FAS only), 44 (dose intensification only) and Week 52 (EOS) | Reduction in disease was measured by PASI score. The PASI 100 response is a 100% improvement (reduction in disease \[PASI 100\]) from baseline in PASI score. The PASI is a measure of the average redness (erythema), thickness (induration), and scaliness (scaling; each graded on a 0-4 scale \[0 = clear; 1-4 = increasing severity\]) of the lesions, weighted by the area of involvement in the four main body areas (i.e., head, arms, trunk to groin, and legs to top of buttocks). The PASI score ranges from 0 to 72. Higher scores represent worse symptom severity. |
| Percentage of Participants With sPGA Responses (0/1) at Week 12 and Week 52 | Week 12 and Week 52 (EOS) | The sPGA is a 6-point scale ranging from 0 (clear) to 5 (very severe) used to measure the severity of disease (induration, scaling, and erythema). A sPGA response was defined as a sPGA value of clear (score 0) or almost clear (score 1). Higher scores represent worse symptom severity. |
| PASI Percent Change at Other Timepoints | Baseline (Day 1 [Week 0]), Weeks 4, 16, 28, 36 (dose intensification only), 40 (re-randomized FAS only), 44 (dose intensification only) and Week 52 (End of Study [EOS]) | The PASI is a measure of the average redness (erythema), thickness (induration), and scaliness (scaling; each graded on a 0-4 scale \[0 = clear; 1-4 = increasing severity\]) of the lesions, weighted by the area of involvement in the four main body areas (i.e., head, arms, trunk to groin, and legs to top of buttocks). The PASI score ranges from 0 to 72. Higher scores represent worse symptom severity. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Day 1 (Week 0) to Week 28; Week 28 to Week 52 (EOS) | TEAEs were summarized by actual treatment received. For each category, participants were included only once, even if they experienced multiple events in that category. |
| Number of Participants With Events of Interests (EOIs) | Day 1 (Week 0) to Week 28; Week 28 to Week 52 (EOS) | The EOIs pre-specified 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, serious depression including suicidality, and venous thromboembolism. |
| Number of Participants Developing Anti-drug Antibodies (ADAs) to ABP 654 | Baseline; Day 1 (Week 0) to Week 28; Week 28 to Week 52 (EOS) | A participant was considered to have developed ADAs if they: * had a positive post-baseline binding or neutralizing antibody result with a negative or no result at Baseline or * had a positive post-baseline binding or neutralizing antibody result with a negative or no result prior to the first dose in the post Week 28 study period. |
| Change From Baseline in Percentage of BSA Affected With Psoriasis at Week 12 and Week 52 | Baseline (Day 1 [Week 0]), Week 12 and Week 52 (EOS) | The percentage of BSA affected was estimated by assuming that the participant's palm, excluding the fingers and thumb, represents roughly 1% of the body's surface. |
Countries
Canada, Estonia, Germany, Hungary, Latvia, Lithuania, Poland, United States
Participant flow
Recruitment details
This study was conducted at 84 centers in Canada, Estonia, Germany, Hungary, Latvia, Lithuania, Poland, and the United States between 11 November 2020 and 03 June 2022.
Pre-assignment details
Of the 648 participants screened, 563 participants were enrolled and randomized in a 1:1 ratio to receive ABP 654 or ustekinumab.
Participants by arm
| Arm | Count |
|---|---|
| Treatment Group A (ABP 654) Participants received SC injection of ABP 654, 45 mg (Baseline BW \<= 100 kg) or 90 mg (Baseline BW \> 100 kg) at Weeks 0, 4, and 16. From Week 28 participants received ABP 654 (same dose) Q12W at Weeks 28 and 40 or, depending on PASI score, received dose intensification Q8W at Weeks 28, 36, and 44 (as per protocol). | 281 |
| Treatment Group B (Ustekinumab) Participants received SC injection of ustekinumab, 45 mg (Baseline BW \<= 100 kg) or 90 mg (Baseline BW \> 100 kg) at Weeks 0, 4, and 16. At Week 28, participants were re-randomized to continue receiving ustekinumab (Treatment group B1), or to receive ABP 654 (Treatment group B2) at Weeks 28 and 40. Depending on PASI score, some participants were not re-randomized and received dose intensification with ustekinumab Q8W at Weeks 28, 36, and 44 (as per protocol). | 282 |
| Total | 563 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 4 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Lost to Follow-up | 4 | 8 |
| Overall Study | Other | 3 | 0 |
| Overall Study | Protocol Violation | 0 | 3 |
| Overall Study | Withdrawal by Subject | 2 | 5 |
Baseline characteristics
| Characteristic | Treatment Group B (Ustekinumab) | Treatment Group A (ABP 654) | Total |
|---|---|---|---|
| Age, Continuous | 45.0 years STANDARD_DEVIATION 12.58 | 43.7 years STANDARD_DEVIATION 14.15 | 44.4 years STANDARD_DEVIATION 13.39 |
| Age, Customized 85 years and over | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Adolescents (12-17 years) | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Adults (18-64 years) | 261 Participants | 257 Participants | 518 Participants |
| Age, Customized Children (2-11 years) | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized From 65-84 years | 21 Participants | 24 Participants | 45 Participants |
| Age, Customized Infants and toddlers (28 days-23 months) | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized In utero | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Newborns (0-27 days) | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Preterm newborn infants (gestational age < 37 wks) | 0 Participants | 0 Participants | 0 Participants |
| PASI | 20.35 Score on a scale STANDARD_DEVIATION 7.85 | 21.50 Score on a scale STANDARD_DEVIATION 8.855 | 20.92 Score on a scale STANDARD_DEVIATION 8.379 |
| Psoriasis Body Surface Area (BSA) | 24.9 Percentage of BSA STANDARD_DEVIATION 15.05 | 26.5 Percentage of BSA STANDARD_DEVIATION 15.25 | 25.7 Percentage of BSA STANDARD_DEVIATION 15.16 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Asian | 25 Participants | 20 Participants | 45 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 4 Participants | 6 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 28 Participants | 32 Participants | 60 Participants |
| Race/Ethnicity, Customized Multiple | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Not allowed to collect | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 252 Participants | 248 Participants | 500 Participants |
| Race/Ethnicity, Customized Other | 5 Participants | 4 Participants | 9 Participants |
| Race/Ethnicity, Customized Unknown | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 247 Participants | 250 Participants | 497 Participants |
| Sex: Female, Male Female | 91 Participants | 104 Participants | 195 Participants |
| Sex: Female, Male Male | 191 Participants | 177 Participants | 368 Participants |
| Static Physician Global Assessment of Psoriasis (sPGA) Score 0 (clear) | 0 Participants | 0 Participants | 0 Participants |
| Static Physician Global Assessment of Psoriasis (sPGA) Score 1 (almost clear) | 0 Participants | 0 Participants | 0 Participants |
| Static Physician Global Assessment of Psoriasis (sPGA) Score 2 (mild) | 0 Participants | 0 Participants | 0 Participants |
| Static Physician Global Assessment of Psoriasis (sPGA) Score 3 (moderate) | 154 Participants | 130 Participants | 284 Participants |
| Static Physician Global Assessment of Psoriasis (sPGA) Score 4 (severe) | 114 Participants | 132 Participants | 246 Participants |
| Static Physician Global Assessment of Psoriasis (sPGA) Score 5 (very severe) | 14 Participants | 19 Participants | 33 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 | 0 / 280 | 1 / 282 | 0 / 247 | 0 / 117 | 0 / 116 | 0 / 25 | 0 / 34 |
| other Total, other adverse events | 21 / 280 | 15 / 282 | 36 / 247 | 22 / 117 | 17 / 116 | 9 / 25 | 2 / 34 |
| serious Total, serious adverse events | 7 / 280 | 5 / 282 | 1 / 247 | 1 / 117 | 3 / 116 | 1 / 25 | 0 / 34 |
Outcome results
Primary
PASI Percent Change From Baseline to Week 12
The PASI is a measure of the average redness (erythema), thickness (induration), and scaliness (scaling; each graded on a 0-4 scale \[0 = clear; 1-4 = increasing severity\]) of the lesions, weighted by the area of involvement in the four main body areas (i.e., head, arms, trunk to groin, and legs to top of buttocks). The PASI score ranges from 0 to 72. Higher scores represent worse symptom severity.
Time frame: Baseline (Day 1 [Week 0]) and Week 12
Population: Results are presented for the FAS with available data; observed data was used for summary statistics.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group A (ABP 654) | PASI Percent Change From Baseline to Week 12 | 81.92 Percent Change in PASI score | Standard Deviation 19.872 |
| Treatment Group B (Ustekinumab) | PASI Percent Change From Baseline to Week 12 | 81.91 Percent Change in PASI score | Standard Deviation 19.611 |
Comparison: Multiple imputation was applied for the point estimate and CI of the mean difference between the 2 groups.95% CI: [-3.16, 3.43]
Secondary
Change From Baseline in Percentage of BSA Affected With Psoriasis at Week 12 and Week 52
The percentage of BSA affected was estimated by assuming that the participant's palm, excluding the fingers and thumb, represents roughly 1% of the body's surface.
Time frame: Baseline (Day 1 [Week 0]), Week 12 and Week 52 (EOS)
Population: Week 12 results are presented for the FAS with available data; LOCF imputation was used. Week 52 results are presented for dose intensification participants with available observed data and re-randomized FAS participants with available data (LOCF imputation was used).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Group A (ABP 654) | Change From Baseline in Percentage of BSA Affected With Psoriasis at Week 12 and Week 52 | Week 52 | -20.6 Percentage of BSA | Standard Deviation 14.72 |
| Treatment Group A (ABP 654) | Change From Baseline in Percentage of BSA Affected With Psoriasis at Week 12 and Week 52 | Week 12 | -17.8 Percentage of BSA | Standard Deviation 14.32 |
| Treatment Group B (Ustekinumab) | Change From Baseline in Percentage of BSA Affected With Psoriasis at Week 12 and Week 52 | Week 52 | -21.6 Percentage of BSA | Standard Deviation 16.89 |
| Treatment Group B (Ustekinumab) | Change From Baseline in Percentage of BSA Affected With Psoriasis at Week 12 and Week 52 | Week 12 | -17.2 Percentage of BSA | Standard Deviation 14.51 |
| Post Week 28: ABP 654/ ABP 654 | Change From Baseline in Percentage of BSA Affected With Psoriasis at Week 12 and Week 52 | Week 52 | -24.7 Percentage of BSA | Standard Deviation 14.81 |
| Post Week 28: Ustekinumab/ ABP 654 | Change From Baseline in Percentage of BSA Affected With Psoriasis at Week 12 and Week 52 | Week 52 | -22.8 Percentage of BSA | Standard Deviation 13.86 |
| Post Week 28: Ustekinumab/ Ustekinumab | Change From Baseline in Percentage of BSA Affected With Psoriasis at Week 12 and Week 52 | Week 52 | -22.5 Percentage of BSA | Standard Deviation 14.11 |
Comparison: Week 12: Treatment Group A vs Treatment Group B.~LOCF imputation was used.95% CI: [-1.15, 2.1]
Comparison: Week 52: Treatment Group A vs Treatment Group B.~Observed data was used.95% CI: [-0.9, 3.67]
Comparison: Week 52: ABP 654 vs Ustekinumab.~LOCF imputation was used.95% CI: [-0.99, 0.74]
Comparison: Week 52: Ustekinumab/ABP 654 vs Ustekinumab.~LOCF imputation was used.95% CI: [-0.9, 1.1]
Secondary
Number of Participants Developing Anti-drug Antibodies (ADAs) to ABP 654
A participant was considered to have developed ADAs if they: * had a positive post-baseline binding or neutralizing antibody result with a negative or no result at Baseline or * had a positive post-baseline binding or neutralizing antibody result with a negative or no result prior to the first dose in the post Week 28 study period.
Time frame: Baseline; Day 1 (Week 0) to Week 28; Week 28 to Week 52 (EOS)
Population: Through Week 28 results are presented for the Safety Analysis Set with available ADA data. Post Week 28 results are presented for the re-randomized Safety Analysis Set and dose intensification participants with available ADA data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment Group A (ABP 654) | Number of Participants Developing Anti-drug Antibodies (ADAs) to ABP 654 | Binding antibody | 52 Participants |
| Treatment Group A (ABP 654) | Number of Participants Developing Anti-drug Antibodies (ADAs) to ABP 654 | Neutralizing antibody | 24 Participants |
| Treatment Group B (Ustekinumab) | Number of Participants Developing Anti-drug Antibodies (ADAs) to ABP 654 | Binding antibody | 104 Participants |
| Treatment Group B (Ustekinumab) | Number of Participants Developing Anti-drug Antibodies (ADAs) to ABP 654 | Neutralizing antibody | 50 Participants |
| Post Week 28: ABP 654/ ABP 654 | Number of Participants Developing Anti-drug Antibodies (ADAs) to ABP 654 | Binding antibody | 11 Participants |
| Post Week 28: ABP 654/ ABP 654 | Number of Participants Developing Anti-drug Antibodies (ADAs) to ABP 654 | Neutralizing antibody | 5 Participants |
| Post Week 28: Ustekinumab/ ABP 654 | Number of Participants Developing Anti-drug Antibodies (ADAs) to ABP 654 | Binding antibody | 4 Participants |
| Post Week 28: Ustekinumab/ ABP 654 | Number of Participants Developing Anti-drug Antibodies (ADAs) to ABP 654 | Neutralizing antibody | 1 Participants |
| Post Week 28: Ustekinumab/ Ustekinumab | Number of Participants Developing Anti-drug Antibodies (ADAs) to ABP 654 | Binding antibody | 2 Participants |
| Post Week 28: Ustekinumab/ Ustekinumab | Number of Participants Developing Anti-drug Antibodies (ADAs) to ABP 654 | Neutralizing antibody | 1 Participants |
| Post Week 28: ABP 654 Dose Intensification | Number of Participants Developing Anti-drug Antibodies (ADAs) to ABP 654 | Binding antibody | 0 Participants |
| Post Week 28: ABP 654 Dose Intensification | Number of Participants Developing Anti-drug Antibodies (ADAs) to ABP 654 | Neutralizing antibody | 0 Participants |
| Post Week 28: Ustekinumab Dose Intensification | Number of Participants Developing Anti-drug Antibodies (ADAs) to ABP 654 | Binding antibody | 2 Participants |
| Post Week 28: Ustekinumab Dose Intensification | Number of Participants Developing Anti-drug Antibodies (ADAs) to ABP 654 | Neutralizing antibody | 1 Participants |
Secondary
Number of Participants With Events of Interests (EOIs)
The EOIs pre-specified 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, serious depression including suicidality, and venous thromboembolism.
Time frame: Day 1 (Week 0) to Week 28; Week 28 to Week 52 (EOS)
Population: Through Week 28 results are presented for the Safety Analysis Set. Post Week 28 results are presented for the re-randomized Safety Analysis Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Group A (ABP 654) | Number of Participants With Events of Interests (EOIs) | 5 Participants |
| Treatment Group B (Ustekinumab) | Number of Participants With Events of Interests (EOIs) | 7 Participants |
| Post Week 28: ABP 654/ ABP 654 | Number of Participants With Events of Interests (EOIs) | 3 Participants |
| Post Week 28: Ustekinumab/ ABP 654 | Number of Participants With Events of Interests (EOIs) | 0 Participants |
| Post Week 28: Ustekinumab/ Ustekinumab | Number of Participants With Events of Interests (EOIs) | 4 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
TEAEs were summarized by actual treatment received. For each category, participants were included only once, even if they experienced multiple events in that category.
Time frame: Day 1 (Week 0) to Week 28; Week 28 to Week 52 (EOS)
Population: Through Week 28 results are presented for the Safety Analysis Set. Post Week 28 results are presented for the re-randomized Safety Analysis Set and the dose intensification participants.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment Group A (ABP 654) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE | 106 Participants |
| Treatment Group A (ABP 654) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any Serious TEAE | 7 Participants |
| Treatment Group B (Ustekinumab) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE | 99 Participants |
| Treatment Group B (Ustekinumab) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any Serious TEAE | 5 Participants |
| Post Week 28: ABP 654/ ABP 654 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE | 85 Participants |
| Post Week 28: ABP 654/ ABP 654 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any Serious TEAE | 1 Participants |
| Post Week 28: Ustekinumab/ ABP 654 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE | 44 Participants |
| Post Week 28: Ustekinumab/ ABP 654 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any Serious TEAE | 1 Participants |
| Post Week 28: Ustekinumab/ Ustekinumab | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE | 40 Participants |
| Post Week 28: Ustekinumab/ Ustekinumab | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any Serious TEAE | 3 Participants |
| Post Week 28: ABP 654 Dose Intensification | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE | 12 Participants |
| Post Week 28: ABP 654 Dose Intensification | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any Serious TEAE | 1 Participants |
| Post Week 28: Ustekinumab Dose Intensification | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE | 9 Participants |
| Post Week 28: Ustekinumab Dose Intensification | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any Serious TEAE | 0 Participants |
Secondary
PASI Percent Change at Other Timepoints
The PASI is a measure of the average redness (erythema), thickness (induration), and scaliness (scaling; each graded on a 0-4 scale \[0 = clear; 1-4 = increasing severity\]) of the lesions, weighted by the area of involvement in the four main body areas (i.e., head, arms, trunk to groin, and legs to top of buttocks). The PASI score ranges from 0 to 72. Higher scores represent worse symptom severity.
Time frame: Baseline (Day 1 [Week 0]), Weeks 4, 16, 28, 36 (dose intensification only), 40 (re-randomized FAS only), 44 (dose intensification only) and Week 52 (End of Study [EOS])
Population: Through Week 28 results are presented for the FAS with available data; last observation carried forward (LOCF) imputation was used. Post Week 28 results are presented for dose intensification participants with available observed data and re-randomized FAS participants with available data (LOCF imputation was used).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Group A (ABP 654) | PASI Percent Change at Other Timepoints | Week 16 | 85.88 Percent Change in PASI score | Standard Deviation 18.704 |
| Treatment Group A (ABP 654) | PASI Percent Change at Other Timepoints | Week 36 | 75.53 Percent Change in PASI score | Standard Deviation 11.038 |
| Treatment Group A (ABP 654) | PASI Percent Change at Other Timepoints | Week 4 | 44.15 Percent Change in PASI score | Standard Deviation 23.587 |
| Treatment Group A (ABP 654) | PASI Percent Change at Other Timepoints | Week 28 | 89.41 Percent Change in PASI score | Standard Deviation 14.228 |
| Treatment Group A (ABP 654) | PASI Percent Change at Other Timepoints | Week 52 | 77.80 Percent Change in PASI score | Standard Deviation 14.76 |
| Treatment Group A (ABP 654) | PASI Percent Change at Other Timepoints | Week 44 | 75.33 Percent Change in PASI score | Standard Deviation 15.563 |
| Treatment Group B (Ustekinumab) | PASI Percent Change at Other Timepoints | Week 44 | 78.42 Percent Change in PASI score | Standard Deviation 14.733 |
| Treatment Group B (Ustekinumab) | PASI Percent Change at Other Timepoints | Week 4 | 42.40 Percent Change in PASI score | Standard Deviation 24.536 |
| Treatment Group B (Ustekinumab) | PASI Percent Change at Other Timepoints | Week 16 | 85.86 Percent Change in PASI score | Standard Deviation 19.953 |
| Treatment Group B (Ustekinumab) | PASI Percent Change at Other Timepoints | Week 28 | 88.18 Percent Change in PASI score | Standard Deviation 18.771 |
| Treatment Group B (Ustekinumab) | PASI Percent Change at Other Timepoints | Week 36 | 74.12 Percent Change in PASI score | Standard Deviation 13.826 |
| Treatment Group B (Ustekinumab) | PASI Percent Change at Other Timepoints | Week 52 | 77.46 Percent Change in PASI score | Standard Deviation 18.109 |
| Post Week 28: ABP 654/ ABP 654 | PASI Percent Change at Other Timepoints | Week 40 | 93.60 Percent Change in PASI score | Standard Deviation 9.738 |
| Post Week 28: ABP 654/ ABP 654 | PASI Percent Change at Other Timepoints | Week 52 | 92.54 Percent Change in PASI score | Standard Deviation 11.808 |
| Post Week 28: Ustekinumab/ ABP 654 | PASI Percent Change at Other Timepoints | Week 40 | 94.22 Percent Change in PASI score | Standard Deviation 8.296 |
| Post Week 28: Ustekinumab/ ABP 654 | PASI Percent Change at Other Timepoints | Week 52 | 93.90 Percent Change in PASI score | Standard Deviation 8.987 |
| Post Week 28: Ustekinumab/ Ustekinumab | PASI Percent Change at Other Timepoints | Week 52 | 93.23 Percent Change in PASI score | Standard Deviation 16.029 |
| Post Week 28: Ustekinumab/ Ustekinumab | PASI Percent Change at Other Timepoints | Week 40 | 95.10 Percent Change in PASI score | Standard Deviation 8.529 |
Comparison: Week 4: Treatment Group A vs Treatment Group B.~LOCF imputation was used.95% CI: [-2.05, 5.94]
Comparison: Week 16: Treatment Group A vs Treatment Group B.~LOCF imputation was used.95% CI: [-2.97, 3.31]
Comparison: Week 28: Treatment Group A vs Treatment Group B.~LOCF imputation was used.95% CI: [-1.39, 4.07]
Comparison: Week 36: Treatment Group A vs Treatment Group B.~Observed data was used.95% CI: [-5.46, 7.98]
Comparison: Week 44: Treatment Group A vs Treatment Group B.~Observed data was used.95% CI: [-10.71, 3.28]
Comparison: Week 52: Treatment Group A vs Treatment Group B.~Observed data was used.95% CI: [-8.45, 7.13]
Comparison: Week 40: ABP 654 vs Ustekinumab.~LOCF imputation was used.95% CI: [-3.42, 0.59]
Comparison: Week 40: Ustekinumab/ABP 654 vs Ustekinumab.~LOCF imputation was used.95% CI: [-3.17, 1.48]
Comparison: Week 52: ABP 654 vs Ustekinumab.~LOCF imputation was used.95% CI: [-3.29, 2.17]
Comparison: Week 52: Ustekinumab/ABP 654 vs Ustekinumab.~LOCF imputation was used.95% CI: [-2.46, 3.86]
Secondary
Percentage of Participants With PASI 100 Response Throughout the Study
Reduction in disease was measured by PASI score. The PASI 100 response is a 100% improvement (reduction in disease \[PASI 100\]) from baseline in PASI score. The PASI is a measure of the average redness (erythema), thickness (induration), and scaliness (scaling; each graded on a 0-4 scale \[0 = clear; 1-4 = increasing severity\]) of the lesions, weighted by the area of involvement in the four main body areas (i.e., head, arms, trunk to groin, and legs to top of buttocks). The PASI score ranges from 0 to 72. Higher scores represent worse symptom severity.
Time frame: Baseline (Day 1 [Week 0]), Weeks 4, 16, 28, 36 (dose intensification only), 40 (re-randomized FAS only), 44 (dose intensification only) and Week 52 (EOS)
Population: Through Week 28 FAS results are presented for the FAS with available data; NRI was used. Post Week 28 results are presented for dose intensification participants with available observed data and re-randomized FAS participants with available data (NRI was used).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment Group A (ABP 654) | Percentage of Participants With PASI 100 Response Throughout the Study | Week 16 | 29.9 Percentage of participants |
| Treatment Group A (ABP 654) | Percentage of Participants With PASI 100 Response Throughout the Study | Week 36 | 0 Percentage of participants |
| Treatment Group A (ABP 654) | Percentage of Participants With PASI 100 Response Throughout the Study | Week 12 | 20.6 Percentage of participants |
| Treatment Group A (ABP 654) | Percentage of Participants With PASI 100 Response Throughout the Study | Week 4 | 0.4 Percentage of participants |
| Treatment Group A (ABP 654) | Percentage of Participants With PASI 100 Response Throughout the Study | Week 28 | 34.5 Percentage of participants |
| Treatment Group A (ABP 654) | Percentage of Participants With PASI 100 Response Throughout the Study | Week 52 | 4.0 Percentage of participants |
| Treatment Group A (ABP 654) | Percentage of Participants With PASI 100 Response Throughout the Study | Week 44 | 4.0 Percentage of participants |
| Treatment Group B (Ustekinumab) | Percentage of Participants With PASI 100 Response Throughout the Study | Week 28 | 31.6 Percentage of participants |
| Treatment Group B (Ustekinumab) | Percentage of Participants With PASI 100 Response Throughout the Study | Week 4 | 0.7 Percentage of participants |
| Treatment Group B (Ustekinumab) | Percentage of Participants With PASI 100 Response Throughout the Study | Week 12 | 19.1 Percentage of participants |
| Treatment Group B (Ustekinumab) | Percentage of Participants With PASI 100 Response Throughout the Study | Week 16 | 26.2 Percentage of participants |
| Treatment Group B (Ustekinumab) | Percentage of Participants With PASI 100 Response Throughout the Study | Week 44 | 2.9 Percentage of participants |
| Treatment Group B (Ustekinumab) | Percentage of Participants With PASI 100 Response Throughout the Study | Week 36 | 0 Percentage of participants |
| Treatment Group B (Ustekinumab) | Percentage of Participants With PASI 100 Response Throughout the Study | Week 52 | 14.7 Percentage of participants |
| Post Week 28: ABP 654/ ABP 654 | Percentage of Participants With PASI 100 Response Throughout the Study | Week 40 | 44.5 Percentage of participants |
| Post Week 28: ABP 654/ ABP 654 | Percentage of Participants With PASI 100 Response Throughout the Study | Week 52 | 47.0 Percentage of participants |
| Post Week 28: Ustekinumab/ ABP 654 | Percentage of Participants With PASI 100 Response Throughout the Study | Week 40 | 41.9 Percentage of participants |
| Post Week 28: Ustekinumab/ ABP 654 | Percentage of Participants With PASI 100 Response Throughout the Study | Week 52 | 42.7 Percentage of participants |
| Post Week 28: Ustekinumab/ Ustekinumab | Percentage of Participants With PASI 100 Response Throughout the Study | Week 52 | 44.8 Percentage of participants |
| Post Week 28: Ustekinumab/ Ustekinumab | Percentage of Participants With PASI 100 Response Throughout the Study | Week 40 | 46.6 Percentage of participants |
Comparison: Week 4: Treatment Group A vs Treatment Group B.~NRI was used.95% CI: [-3.16, 3.21]
Comparison: Week 12: Treatment Group A vs Treatment Group B.~NRI was used.95% CI: [-5.03, 8.18]
Comparison: Week 16: Treatment Group A vs Treatment Group B.~NRI was used.95% CI: [-3.62, 11.17]
Comparison: Week 28: Treatment Group A vs Treatment Group B.~NRI was used.95% CI: [-4.68, 10.78]
Comparison: Week 40: ABP 654 vs Ustekinumab.~NRI was used.95% CI: [-12.85, 8.89]
Comparison: Week 40: Ustekinumab/ABP 654 vs Ustekinumab.~NRI was used.95% CI: [-17.39, 7.73]
Comparison: Week 52: ABP 654 vs Ustekinumab.~NRI was used.95% CI: [-8.42, 13.3]
Comparison: Week 52: Ustekinumab/ABP 654 vs Ustekinumab.~NRI was used.95% CI: [-14.91, 10.19]
Secondary
Percentage of Participants With PASI 75 Response Throughout the Study
Reduction in disease was measured by PASI score. The PASI 75 response is a 75% or greater improvement (reduction in disease \[PASI 75\]) from baseline in PASI score. The PASI is a measure of the average redness (erythema), thickness (induration), and scaliness (scaling; each graded on a 0-4 scale \[0 = clear; 1-4 = increasing severity\]) of the lesions, weighted by the area of involvement in the four main body areas (i.e., head, arms, trunk to groin, and legs to top of buttocks). The PASI score ranges from 0 to 72. Higher scores represent worse symptom severity.
Time frame: Baseline (Day 1 [Week 0]), Weeks 4, 16, 28, 36 (dose intensification only), 40 (re-randomized FAS only), 44 (dose intensification only) and Week 52 (EOS)
Population: Through Week 28 FAS results are presented for the FAS with available data; non-responder imputation (NRI) was used. Post Week 28 results are presented for dose intensification participants with available observed data and re-randomized FAS participants with available data (NRI was used).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment Group A (ABP 654) | Percentage of Participants With PASI 75 Response Throughout the Study | Week 16 | 80.8 Percentage of participants |
| Treatment Group A (ABP 654) | Percentage of Participants With PASI 75 Response Throughout the Study | Week 36 | 52.0 Percentage of participants |
| Treatment Group A (ABP 654) | Percentage of Participants With PASI 75 Response Throughout the Study | Week 12 | 69.8 Percentage of participants |
| Treatment Group A (ABP 654) | Percentage of Participants With PASI 75 Response Throughout the Study | Week 4 | 11.4 Percentage of participants |
| Treatment Group A (ABP 654) | Percentage of Participants With PASI 75 Response Throughout the Study | Week 28 | 85.8 Percentage of participants |
| Treatment Group A (ABP 654) | Percentage of Participants With PASI 75 Response Throughout the Study | Week 52 | 64.0 Percentage of participants |
| Treatment Group A (ABP 654) | Percentage of Participants With PASI 75 Response Throughout the Study | Week 44 | 48.0 Percentage of participants |
| Treatment Group B (Ustekinumab) | Percentage of Participants With PASI 75 Response Throughout the Study | Week 28 | 82.3 Percentage of participants |
| Treatment Group B (Ustekinumab) | Percentage of Participants With PASI 75 Response Throughout the Study | Week 4 | 10.3 Percentage of participants |
| Treatment Group B (Ustekinumab) | Percentage of Participants With PASI 75 Response Throughout the Study | Week 12 | 70.2 Percentage of participants |
| Treatment Group B (Ustekinumab) | Percentage of Participants With PASI 75 Response Throughout the Study | Week 16 | 80.1 Percentage of participants |
| Treatment Group B (Ustekinumab) | Percentage of Participants With PASI 75 Response Throughout the Study | Week 44 | 64.7 Percentage of participants |
| Treatment Group B (Ustekinumab) | Percentage of Participants With PASI 75 Response Throughout the Study | Week 36 | 55.9 Percentage of participants |
| Treatment Group B (Ustekinumab) | Percentage of Participants With PASI 75 Response Throughout the Study | Week 52 | 58.8 Percentage of participants |
| Post Week 28: ABP 654/ ABP 654 | Percentage of Participants With PASI 75 Response Throughout the Study | Week 40 | 94.7 Percentage of participants |
| Post Week 28: ABP 654/ ABP 654 | Percentage of Participants With PASI 75 Response Throughout the Study | Week 52 | 89.5 Percentage of participants |
| Post Week 28: Ustekinumab/ ABP 654 | Percentage of Participants With PASI 75 Response Throughout the Study | Week 40 | 95.7 Percentage of participants |
| Post Week 28: Ustekinumab/ ABP 654 | Percentage of Participants With PASI 75 Response Throughout the Study | Week 52 | 92.3 Percentage of participants |
| Post Week 28: Ustekinumab/ Ustekinumab | Percentage of Participants With PASI 75 Response Throughout the Study | Week 52 | 92.2 Percentage of participants |
| Post Week 28: Ustekinumab/ Ustekinumab | Percentage of Participants With PASI 75 Response Throughout the Study | Week 40 | 94.0 Percentage of participants |
Comparison: Week 4: Treatment Group A vs Treatment Group B.~NRI was used.95% CI: [-4.02, 6.42]
Comparison: Week 12: Treatment Group A vs Treatment Group B.~NRI was used.95% CI: [-7.87, 7.23]
Comparison: Week 16: Treatment Group A vs Treatment Group B.~NRI was used.95% CI: [-5.75, 7.37]
Comparison: Week 28: Treatment Group A vs Treatment Group B.~NRI was used.95% CI: [-2.37, 9.84]
Comparison: Week 36: Treatment Group A vs Treatment Group B.~Observed data was used.95% CI: [-28.15, 21.76]
Comparison: Week 40: ABP 654 vs Ustekinumab.~NRI was used.95% CI: [-3.74, 7.54]
Comparison: Week 40: Ustekinumab/ABP 654 vs Ustekinumab.~NRI was used.95% CI: [-4.89, 8.39]
Comparison: Week 52: ABP 654 vs Ustekinumab.~NRI was used.95% CI: [-8.61, 4.41]
Comparison: Week 52: Ustekinumab/ABP 654 vs Ustekinumab.~NRI was used.95% CI: [-7.32, 7.43]
Secondary
Percentage of Participants With sPGA Responses (0/1) at Week 12 and Week 52
The sPGA is a 6-point scale ranging from 0 (clear) to 5 (very severe) used to measure the severity of disease (induration, scaling, and erythema). A sPGA response was defined as a sPGA value of clear (score 0) or almost clear (score 1). Higher scores represent worse symptom severity.
Time frame: Week 12 and Week 52 (EOS)
Population: Week 12 results are presented for the FAS with available data; NRI was used. Week 52 results are presented for dose intensification participants with available data and re-randomized FAS participants with available data (NRI was used).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment Group A (ABP 654) | Percentage of Participants With sPGA Responses (0/1) at Week 12 and Week 52 | Week 52 | 24.0 Percentage of participants |
| Treatment Group A (ABP 654) | Percentage of Participants With sPGA Responses (0/1) at Week 12 and Week 52 | Week 12 | 55.2 Percentage of participants |
| Treatment Group B (Ustekinumab) | Percentage of Participants With sPGA Responses (0/1) at Week 12 and Week 52 | Week 52 | 35.3 Percentage of participants |
| Treatment Group B (Ustekinumab) | Percentage of Participants With sPGA Responses (0/1) at Week 12 and Week 52 | Week 12 | 52.8 Percentage of participants |
| Post Week 28: ABP 654/ ABP 654 | Percentage of Participants With sPGA Responses (0/1) at Week 12 and Week 52 | Week 52 | 71.3 Percentage of participants |
| Post Week 28: Ustekinumab/ ABP 654 | Percentage of Participants With sPGA Responses (0/1) at Week 12 and Week 52 | Week 52 | 70.9 Percentage of participants |
| Post Week 28: Ustekinumab/ Ustekinumab | Percentage of Participants With sPGA Responses (0/1) at Week 12 and Week 52 | Week 52 | 78.4 Percentage of participants |
Comparison: Week 12: Treatment Group A vs Treatment Group B.~NRI was used.95% CI: [-5.65, 10.71]
Comparison: Week 52: ABP 654 vs Ustekinumab.~NRI was used.95% CI: [-15.41, 3.29]
Comparison: Week 52: ABP 654/Ustekinumab vs Ustekinumab.~NRI was used.95% CI: [-18.41, 3.74]