| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Moderate to severe plaque psoriasis |
|
| E.1.1.1 | Medical condition in easily understood language |
| Moderate to severe plaque psoriasis |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10071117 |
| E.1.2 | Term | Plaque psoriasis |
| E.1.2 | System Organ Class | 100000004858 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To demonstrate similarity of pharmacokinetics in subjects with multiple switches between ustekinumab and ABP 654 compared to subjects receiving continued use of ustekinumab |
|
| E.2.2 | Secondary objectives of the trial |
| To assess the efficacy, safety and immunogenicity in subjects with multiple switches between ABP 654 and ustekinumab compared with subjects receiving continued use of ustekinumab |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Subject is male or female and is ≥ 18 and ≤ 75 years of age inclusive, at the time of enrollment.
2. Subject has stable moderate to severe plaque psoriasis for at least 6 months (eg, no morphology changes or significant flares of disease activity in the opinion of the investigator).
3. Subject has a score of PASI ≥ 12, involvement of ≥ 10% body surface area (BSA) and static Physician Global Assessment (sPGA) ≥ 3 at screening and at baseline.
4. Subject is a candidate for phototherapy or systemic therapy.
5. Subject has previous failure, inadequate response, intolerance, or contraindication to at least 1 conventional antipsoriatic systemic therapy (eg, methotrexate, cyclosporine, psoralen plus ultraviolet light [PUVA]).
6. Female subject (except if at least 2 years postmenopausal or surgically sterile): a negative serum pregnancy test during screening and a negative urine pregnancy test at baseline.
7. Subject or legally acceptable representative is capable of giving signed Institutional Review Board (IRB)/Independent Ethics Committee (IEC) informed consent.
8. Subject has no known history of latent or active tuberculosis. Subject must meet any 1 of the following 3 criteria:
• Subject has a negative test for tuberculosis during screening, defined as either:
o Negative purified protein derivative (PPD); < 5 mm of induration at 48 hours to 72 hours after test is placed, or
o Negative Quantiferon®/T-spot® test.
• Subject with a positive PPD test and a history of Bacillus Calmette-Guérin (BCG)
vaccination is allowed with a negative Quantiferon/T-spot test
• Subject with a positive PPD test (without a history of BCG vaccination) or subject with a positive or indeterminate Quantiferon/T-spot test is allowed if he/she has all of the following:
o No symptoms per tuberculosis worksheet provided by the sponsor, Amgen Inc.
o Documented history of adequate prophylaxis initiation prior to receiving investigational product in accordance with local recommendations
o No known exposure to a case of active tuberculosis after most recent prophylaxis
o No evidence of active tuberculosis on chest radiograph within 3 months prior to the first dose of investigational product |
|
| E.4 | Principal exclusion criteria |
Skin Disease Related Conditions
1. Subject 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.
Other Medical Conditions
2. Subject has a planned surgical intervention during the duration of the study.
3. Subject has an active infection or history of infections, as follows:
a. Any active infection for which systemic anti-infectives were used within 28 days prior to enrollment
b. Serious infection, defined as requiring hospitalization or IV anti-infectives within 8 weeks prior to enrollment
c. Recurrent or chronic infections or other active infection that, in the opinion of the investigator, might cause this study to be detrimental to the subject
4. Subject has known history or tests positive of HIV at screening.
5. Subject has hepatitis B surface antigen or hepatitis C virus antibody positivity at screening.
6. Subject has uncontrolled, clinically significant systemic disease, such as uncontrolled diabetes mellitus, cardiovascular disease, renal disease, liver disease, or hypertension.
7. Subject has known malignancy within the previous 5 years (except treated or considered cured cutaneous squamous or basal cell carcinoma, in situ cervical cancer, or in situ breast ductal carcinoma).
8. Subject has active neurological disease, such as multiple sclerosis, Guillain Barre syndrome, optic neuritis, transverse myelitis, or history of neurologic symptoms suggestive of central nervous system demyelinating disease.
9. Subject has a mean QT internal or abnormal long QTcF of > 450 msec (male) or > 470 msec (female) at baseline that, in the opinion of the investigator, is abnormal or clinically significant.
10. Subject has moderate to severe heart failure (New York Heart Associate class III/IV).
11. Subject has known hypersensitivity to the investigational product or to any of the excipients.
12. Subject has any concurrent medical condition that, in the opinion of the investigator, could cause this study to be detrimental to the subject.
Laboratory Abnormalities
13. Subject has laboratory abnormalities at screening, including any of the following:
a. Hemoglobin < 9 g/dL
b. Platelet count < 100,000/mm3
c. White blood cell count < 3,000 cells/mm3
d. Aspartate aminotransferase and/or alanine aminotransferase ≥ 2.0 × the upper limit of normal
e. Creatinine clearance < 50 mL/min (Cockcroft Gault formula)
f. Any other laboratory abnormality which, in the opinion of the investigator, will prevent the subject from completing the study or will interfere with the interpretation of the study results
Washouts and Non-permitted Drugs
14. Subject has had previous treatment with any agent specifically targeting IL-12 or IL-23 within 1 year prior to enrollment.
15. Subject has received biologic treatment for psoriasis within the previous month or 5 drug half-lives (whichever is longer) prior to enrollment.
16. Subject has received any investigational agents within the previous month or 5 half-lives (whichever is longer) prior to enrollment.
17. Subject has received non-biologic systemic psoriasis therapy within 4 weeks prior to enrollment.
18. Subject 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.
19. Subject has received topical psoriasis treatment within 2 weeks prior to enrollment.
20. Subject has received live viral or live bacterial vaccination within 2 weeks prior to enrollment.
21. Subject has received BCG vaccination within 1 year prior to enrollment.
22. Subject has received other investigational procedures within 4 weeks prior to enrollment and during the course of the study.
General
23. Subject has active substance abuse within 24 weeks prior to enrollment.
24. Female subject 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.
25. Sexually active subjects and their partners who are of childbearing potential and not agreeing to use adequate contraception while participating in the study and for 5 months after the last dose of investigational product. Male subjects must agree not to donate sperm during the study and for 5 months following after last dose of investigational product or until the scheduled EOS visit (whichever is longer).
26. Subject is not likely to comply with all required study procedures (eg, Clinical Outcome Assessments) to the best of the subject and investigator knowledge.
27. Subject has any physical or psychiatric disorder that, in the opinion of the investigator, may compromise the ability of the subject to give informed consent and/or to comply with all the required study procedures. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Pharmacokinetic parameters:
• AUCtau between week 52 and week 64
• Cmax between week 52 and week 64 |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| between week 52 and week 64 |
|
| E.5.2 | Secondary end point(s) |
Pharmacokinetic-related Endpoints:
• tmax between week 52 and week 64
• Ctrough,ss between week 28 and week 52
Efficacy-related Endpoints:
• PASI percent improvement from baseline (day 1) to week 64
• PASI 75 response at week 64
• PASI 100 response at week 64
Safety-related Endpoints:
• Treatment-emergent adverse events and serious adverse events, post randomization
• Events of interest, post randomization
• Incidence of antidrug antibodies, post randomization |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Pharmacokinetic-related Endpoints:
• between week 52 and week 64
• between week 28 and week 52
Efficacy-related Endpoints:
• week 64
• week 64
• week 64
Safety-related Endpoints:
• post randomization
• post randomization
• post randomization |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| Immunogenicity, interchangeability |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 69 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Canada |
| United States |
| Georgia |
| Serbia |
| Estonia |
| Germany |
| Hungary |
| Latvia |
| Poland |
| Spain |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| The end of the study is defined as the date of the last visit of the last subject in the study or last scheduled procedure shown in the Schedule of Assessments for the last subject in the study globally. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 1 |
Print
