A Study to Investigate Interchangeability of ABP 654 for the Treatment of Participants With Moderate to Severe Plaque Psoriasis

Phase 3

Completed

Conditions: Psoriasis

Interventions: Drug: Ustekinumab
Drug: ABP 654

Registration Number: NCT04761627

Lead Sponsor: Amgen

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 494

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Switching Group (Ustekinumab - ABP 654)	ABP 654	Participants will initially receive injection of ustekinumab up to Week 16. Thereafter, starting from Week 28, participants will switch between ABP 654 and ustekinumab every 12 weeks up to Week 52.
Continued-use Group (Ustekinumab)	Ustekinumab	Participants will receive subcutaneous injection of ustekinumab up to Week 52.
Switching Group (Ustekinumab - ABP 654)	Ustekinumab	Participants will initially receive injection of ustekinumab up to Week 16. Thereafter, starting from Week 28, participants will switch between ABP 654 and ustekinumab every 12 weeks up to Week 52.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.
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.
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.
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.
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.
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.
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.

Trial Locations

Locations (88): Enverus Medical Research
🇨🇦
Surrey, British Columbia, Canada
Guelph Dermatology Research
🇨🇦
Guelph, Ontario, Canada
Center for Clinical Studies, LTD., LLP
🇺🇸
Webster, Texas, United States
North York Research Inc. - Dermatology
🇨🇦
North York, Ontario, Canada
SimcoDerm Medical and Surgical Dermatology Center
🇨🇦
Barrie, Ontario, Canada
CCA Medical Research
🇨🇦
Ajax, Ontario, Canada
Praxis Hoffmann
🇩🇪
Witten, Nordrhein-Westfalen, Germany
Dr. Irina Turchin PC Inc.
🇨🇦
Fredericton, New Brunswick, Canada
Dr Wei Jing Loo Medicine Professional Corporation
🇨🇦
London, Ontario, Canada
Wiseman Dermatology Research Inc.
🇨🇦
Winnipeg, Manitoba, Canada
ETG Siedlce
🇵🇱
Siedlce, Poland
Rothhaar Studien GmbH
🇩🇪
Berlin, Germany
Dermazentrum Augsburg
🇩🇪
Augsburg, Bayern, Germany
,,Tbilisi Cancer center"LTD
🇬🇪
Tbilisi, T'bilisi, Georgia
Debreceni Egyetem Klinikai Központ Nagyerdei Campus
🇭🇺
Debrecen, Hajdú-Bihar, Hungary
Fachklinik Bad Bentheim
🇩🇪
Bad Bentheim, Niedersachsen, Germany
Confido Private Medical Clinic - General Practice/Medicine
🇪🇪
Tallinn, Harjumaa, Estonia
Dermatology Ottawa Research Centre
🇨🇦
Ottawa, Ontario, Canada
Universitätsklinikum Frankfurt am Main - Klinik für Dermatol
🇩🇪
Frankfurt/Main, Hessen, Germany
Klinische Forschung Dresden GmbH
🇩🇪
Dresden, Sachsen, Germany
MICS Centrum Medyczne Bydgoszcz
🇵🇱
Bydgoszcz, Poland
Krakowskie Centrum Medyczne Sp. z o.o.
🇵🇱
Krakow, Poland
Lynderm Research Inc
🇨🇦
Markham, Ontario, Canada
DermEdge Research Inc.
🇨🇦
Mississauga, Ontario, Canada
Dr. S. K. Siddha Medicine Professional Corporation - Doctor's Office
🇨🇦
Newmarket, Ontario, Canada
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
Encore Research Group-Jacksonville Center for Clinical Resea
🇺🇸
Jacksonville, Florida, United States
Southern California Dermatology, Inc
🇺🇸
Santa Ana, California, United States
Altus Research, Inc.
🇺🇸
Lake Worth, 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
Hamilton Research, LLC
🇺🇸
Alpharetta, Georgia, United States
Olympian Clinical Research
🇺🇸
Tampa, Florida, United States
Advanced Medical Research PC
🇺🇸
Sandy Springs, Georgia, United States
Dundee Dermatology
🇺🇸
West Dundee, Illinois, United States
DS Research
🇺🇸
Clarksville, Indiana, United States
Integrated Clinical Trial Services Inc.
🇺🇸
West Des Moines, Iowa, United States
Kansas Medical Clinic, PA
🇺🇸
Topeka, Kansas, United States
Clinical Pharmacology Study Group
🇺🇸
Worcester, Massachusetts, United States
Hamzavi Dermatology
🇺🇸
Fort Gratiot, Michigan, United States
Minnesota Clinical Study Center
🇺🇸
New Brighton, Minnesota, United States
MediSearch Clinical Trials
🇺🇸
Saint Joseph, Missouri, United States
Psoriasis Treatment Center of Central New Jersey
🇺🇸
East Windsor, New Jersey, United States
Wilmington Dermatology Center
🇺🇸
Wilmington, North Carolina, United States
Oregon Medical Research Center
🇺🇸
Portland, Oregon, United States
Austin Institute for Clinical Research, Inc.
🇺🇸
Dripping Springs, Texas, United States
Austin Institute for Clinical Research, Inc - Dermatology
🇺🇸
Pflugerville, Texas, United States
International Dermatology Research, Inc.
🇺🇸
Miami, Florida, United States
Progressive Clinical Research [Texas]
🇺🇸
San Antonio, Texas, United States
UK-SH - Lübeck
🇩🇪
Lübeck, Schleswig-Holstein, Germany
Burke Pharmaceutical Research
🇺🇸
Hot Springs, Arkansas, United States
ActivMed Practices & Research, LLC.
🇺🇸
Portsmouth, New Hampshire, United States
LTD Aversi Clinic
🇬🇪
Tbilisi, T'bilisi, Georgia
Acad.Fridon Todua Medical Center- Research Institute of Clinical Medicine
🇬🇪
Tbilisi, T'bilisi, Georgia
LTD Israeli-Georgian Medical Research Clinic Helsicore
🇬🇪
Tbilisi, T'bilisi, Georgia
Smite Aija doctor practice in dermatology, venereology
🇱🇻
Talsi, Latvia
RENEW CLINIC Spolka Jawna
🇵🇱
Bialystok, Poland
RCMed Oddzia Warszawa
🇵🇱
Warszawa, Poland
DermMedica Sp. z o.o.
🇵🇱
Wroclaw, Poland
Skin Specialists PC
🇺🇸
Omaha, Nebraska, United States
Innomedica OÜ
🇪🇪
Tallinn, Estonia
Centrum Medyczne Plejady
🇵🇱
Krakow, Maopolskie, Poland
Twoja Przychodnia - Szczecinskie Centrum Medyczne
🇵🇱
Szczecin, Poland
Centrum Medyczne Evimed
🇵🇱
Warszawa, Poland
The Dermatology Group, PC
🇺🇸
Verona, New Jersey, United States
Clinical Research Center
🇪🇪
Tartu, Tartumaa, Estonia
Dermatologische Gemeinschaftspraxis Dres.Scholz Sebastian Schilling
🇩🇪
Mahlow, Brandenburg, Germany
Qualiclinic Kft
🇭🇺
Budapest, Pest, Hungary
Riga 1st hospital, Clinic of Dermatology and STD
🇱🇻
Riga, Rga, Latvia
Centrum Medyczne Pratia Gdynia
🇵🇱
Gdynia, Poland
Centrum Medyczne PROMED
🇵🇱
Krakow, Poland
Barbara Rewerska Diamond Clinic
🇵🇱
Krakow, Poland
Tartu University Hospital
🇪🇪
Tartu, Tartumaa, Estonia
,,KANVENI - Scientific/Research National Center of Dermatology and Venereology LLC
🇬🇪
Tbilisi, Georgia
J.Kisis LtD
🇱🇻
Riga, Rga, Latvia
Centrum Medyczne ALL-MED Badania Kliniczne
🇵🇱
Krakow, Maopolskie, Poland
Centrum Medyczne Pratia Bydgoszcz
🇵🇱
Bydgoszcz, Poland
RCMed Oddzial Sochaczew
🇵🇱
Sochaczew, Poland
Derma-Study-Center-FN
🇩🇪
Friedrichshafen, Baden-Württemberg, Germany
Brgyógyászati és Allergológiai Magánrendelés
🇭🇺
Szolnok, Jász-Nagykun-Szolnok, Hungary
UNOMEDICALTRIALS Kft
🇭🇺
Budapest, Pest, Hungary
MICS Centrum Medyczne Warszawa
🇵🇱
Warszawa, Mazowieckie, Poland
Research Toronto
🇨🇦
Toronto, Ontario, Canada
K. Papp Clinical Research Inc.
🇨🇦
Waterloo, Ontario, Canada
Universitätsklinikum Carl Gustav Carus
🇩🇪
Dresden, Sachsen, Germany
Charite - Campus Charite Mitte (CCM) - Dermatologie & Allergologie - Dermatologie & Allergologie
🇩🇪
Berlin, Germany