| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Moderate to Severe Chronic Plaque Psoriasis |
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| E.1.1.1 | Medical condition in easily understood language |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
| 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 |
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| 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 equivalent efficacy between Bmab 1200 and Stelara® in patients with moderate to severe chronic plaque psoriasis. |
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| E.2.2 | Secondary objectives of the trial |
- To assess the efficacy of Bmab 1200 based on other efficacy parameters and timepoints over the study period as compared with Stelara®;
- To assess the safety and tolerability of Bmab 1200 as compared with Stelara® over the study period;
- To assess the immunogenicity of Bmab 1200 as compared with Stelara® over the study period;
- To assess the PK of Bmab 1200 as compared with Stelara®;
- To assess the safety and immunogenicity after switching from Stelara® to Bmab 1200;
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|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Patient is willing and able to provide informed consent form (ICF), able to follow study instructions, and comply with the protocol requirements as per the investigator’s opinion;
2. Patient is aged 18 to 80 years, both inclusive, and weighing <130 kg at the time of the screening visit;
3. Patient has a diagnosis of chronic plaque psoriasis for at least 6 months and is a candidate for systemic therapy or phototherapy at the time of the screening visit;
4. Patient with moderate to severe chronic plaque psoriasis as defined by BSA involvement ≥10%, PASI score ≥12, and sPGA ≥3 at the screening and baseline visits;
5. Patient has stable disease for at least 2 months before the baseline visit;
6. Patient has adequate renal and hepatic function at the screening
7. Patient has the following hematology laboratory test results at screening:
a) Hemoglobin ≥10.0 g/dL;
b) Absolute neutrophil count ≥1500/μL (SI units: ≥1.5 × 10^9 cells/L);
c) Platelet count ≥100 000/μL (SI units: ≥100 × 10^9 cells/L);
8. Patient has had a previous failure, inadequate response, intolerance, or contraindication to at least one antipsoriatic systemic therapy;
9. Women of childbearing potential must have a negative serum pregnancy test during screening and a negative urine pregnancy test at baseline. A female patient is considered not of childbearing potential when postmenopausal (at least 12 consecutive months without menses without an alternative medical cause) or surgically sterilized (hysterectomy, bilateral salpingectomy, and bilateral oophorectomy);
10. Women of childbearing potential and male patients with a female partner of childbearing potential must be willing to use highly effective contraceptive precautions which are consistent with local regulations regarding the use of birth control methods for patients participating in clinical studies throughout the study period and continuing for at least 15 weeks after the last dose of study drug. Please refer to APPENDIX 1 of protocol for acceptable highly effective contraceptive methods. Abstinence from heterosexual intercourse is accepted when this is the usual lifestyle of the patient and must be continued for at least 15 weeks after the last dose of study drug. |
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| E.4 | Principal exclusion criteria |
1. Patient has nonplaque psoriasis, such as erythrodermic psoriasis, pustular psoriasis, guttate psoriasis, medication-induced psoriasis, other skin conditions (eg, eczema), other current or chronic systemic autoimmune or inflammatory disease at the time of screening visit that would interfere with the evaluation of the effect of the study treatment of psoriasis. Patients with concurrent psoriatic arthritis will be allowed to participate;
2. Patient who has a current or past history of any of the following infections:
a) Current or past history of congenital or acquired immunodeficiency or patient is positive for the human immunodeficiency virus (HIV) antibodies (HIV-1 or HIV-2) at screening;
b) Patient has current infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) as per serological tests at screening;
c) Presence of active infection at screening or history of infection requiring intravenous antibiotics and/or hospitalization ≤8 weeks before baseline visit, or oral/intramuscular antibiotics ≤4 weeks before baseline visit, or topical antibiotics ≤2 weeks before baseline visit. Minor localized fungal infections or topical antibiotics for facial acne may be allowed;
d) Any recurrent bacterial, fungal, opportunistic, or viral infection including recurrent/disseminated herpes zoster that, based on the investigator´s clinical assessment, causes a safety risk and makes the patient unsuitable for the study;
e) History of invasive/systemic fungal infection (eg, histoplasmosis) or nontubercular mycobacterial infection.
3. Patient meeting any of the following tuberculosis (TB)-related conditions:
a) Patient who has current or history of active TB.
b) Patient who has signs or symptoms suggestive of active TB upon medical history or physical examination including chest radiography at screening.
c) Patients with current latent TB d) Patient who has had exposure to a person with active TB, such as first-degree family members or coworkers within 16 weeks before the baseline visit.
4. Patient has an underlying condition (including, but not limited to metabolic, hematologic, renal, hepatic, pulmonary, neurologic including central nervous system demyelinating disease, endocrine, cardiac, infection, or gastrointestinal) which, in the opinion of the investigator, significantly immune-compromises the patient and/or places the patient at unacceptable risk for receiving an immunomodulatory therapy.
5. Patient had a major surgical intervention within 12 weeks of the baseline or planned major surgery during the study period.
6. Patient who has prior exposure to more than 1 biologic agent for the treatment of psoriasis or psoriatic arthritis.
7. Patient who has received or plans to receive any of the following prohibited medications or treatment that could affect psoriasis:
a) Topical therapies for the treatment of psoriasis within 2 weeks before the baseline visit.
b) Ultraviolet A phototherapy (with or without oral psoralen) or ultraviolet B phototherapy for the treatment of psoriasis within 4 weeks before the baseline visit.
c) Systemic steroids within 4 weeks before the baseline visit.
d) Any nonbiologic systemic therapies for the treatment of psoriasis or psoriatic arthritis within 4 weeks before the baseline visit.
e) Any biologic systemic therapy with a mechanism of action that could impact the course of psoriasis/psoriatic arthritis or its evaluations, within 5 half-lives or 90 days, whichever is longer, before the baseline visit.
f) Any monoclonal antibody (mAb) within 5 half-lives or 90 days, whichever is longer, before the baseline visit.
g) Any drug that directly targets interleukin (IL)-12, IL-17, or IL-23 including ustekinumab either investigational or approved.
h) Any investigational drug other than study treatment within 4 weeks or 5 half-lives (whichever is longer) before the baseline visit.
i) Any other drug that may impact psoriasis (eg, beta-blockers, lithium, antimalarials) within 4 weeks before the baseline visit.
j) Herbal or any nonpharmaceutical medicine to treat psoriasis within 2 weeks before the baseline visit.
8. Patient has received a live or live-attenuated vaccine within 4 weeks before the baseline visit.
9. Patient who has had Bacillus Calmette-Guérin (BCG) vaccination within 1 year before the baseline visit.
10. Patient who had confirmed coronavirus disease 2019 (COVID-19) infection and was hospitalized requiring oxygen in the last 8 weeks prior to screening. In case of asymptomatic/mildly symptomatic patient with confirmed COVID-19 infection during the last 4 weeks prior to screening, and who have not recovered from COVID-19 as per site and/ local regulatory guidelines at screening, would also be excluded from the study.
11. Patient who has received or is planning to receive COVID-19 vaccination within 2 weeks before or after the baseline visit.
For the complete list of exclusion criteria, please refer to the clinical trial protocol |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| Percentage change from baseline in the Psoriasis Area and Severity Index (PASI) score at Week 12 (Time Frame: Baseline [Day 1] to Week 12). |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
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| E.5.2 | Secondary end point(s) |
Secondary Endpoints:
Efficacy Endpoints:
•Percentage change from baseline in the PASI score at Weeks 4, 8, 16, 20, and 28, 40, and 52 (Time Frame: Baseline [Day 1] through Weeks 28 and 52).
•PASI improvement of ≥50% relative to baseline (PASI 50) , PASI improvement of ≥75% relative to baseline (PASI 75), and PASI improvement of ≥90% relative to baseline (PASI 90) at Weeks 4, 8, 12, 16, 20, and 28, 40, and 52 (Time Frame: Baseline [Day 1] through Weeks 28 and 52).
•Static Physician’s Global Assessment (sPGA) response of cleared or almost clear/minimal (PGA of 0 or 1) at Weeks 4, 8, 12, 16, 20, and 28, 40, and 52 (Time Frame: Baseline [Day 1] through Weeks 28 and 52).
•Area under effect curves (AUECs) of PASI score from baseline to Week 12 (Time Frame: Baseline [Day 1] through Week 12).
•Raw PASI scores at Weeks 4, 8, 12, 16, 20, and 28, 40, and 52 (Time Frame: Baseline [Day 1] through Weeks 28 and 52).
•Change from baseline in affected body surface area (BSA) at Weeks 4, 8, 12, 16, 20, and 28, 40, and 52 (Time Frame: Baseline [Day 1] through Weeks 28 and 52).
•Change from baseline in quality of life (QoL) as measured by Dermatology Life Quality Index (DLQI) scores at Weeks 4, 8, 12, 16, 20, and 28, 40, and 52 (Time Frame: Baseline [Day 1] through Weeks 28 and 52).
Safety Endpoints:
•Treatment-emergent adverse events (TEAEs) including adverse events of special interest (AESIs) and adverse reactions (ADRs) during the treatment periods (Time Frame: Baseline [Day 1] through Weeks 28 and 52).
•Injection site reactions and hypersensitivity at Day 1, Week 4, Week 16, Week 28, Week 40, and throughout the study (Time Frame: Baseline [Day 1] through Weeks 28 and 52).
•Other safety endpoints as follows (Time Frame: Baseline [Day 1] through Weeks 28 and 52):
•Absolute values and changes from baseline in Clinical laboratory assessments (hematology, clinical chemistry, and urinalysis)Vital sign parameters (systolic and diastolic blood pressure, pulse rate, respiratory rate, and body temperature) 12-lead electrocardiogram (ECG)
•Physical examination
Immunogenicity Endpoints:
•Proportion of patients developing antidrug antibodies (ADAs) and neutralizing antibodies (NAbs) during treatment period 1 (TP1) (Time Frame: Baseline [Day 1] through Week 16).
•Proportion of patients developing ADAs and NAbs during treatment period 2 (TP2) (Time Frame: post rerandomization/dosing on Week 16 through Week 28 predosing).
•Proportion of patients developing ADAs and NAbs during treatment period 3 (TP3) (Time Frame: post dosing on Week 28 through Week 52).
Pharmacokinetic (PK) Endpoints:
•Serum concentrations of ustekinumab during TP1 (Time Frame: Baseline [Day 1] through Week 16).
•Serum concentrations of ustekinumab during TP2 (Time Frame: post rerandomization/dosing on Week 16 through Week 28 predosing).
•Serum concentrations of ustekinumab during TP3 (Time Frame: post dosing on Week 28 through Week 52).
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|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| As specified within the list of endpoints |
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| 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 | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | Yes |
| 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 and tolerability |
|
| 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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 28 |
| 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 |
| Georgia |
| United States |
| Estonia |
| Latvia |
| Poland |
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| E.8.7 | Trial has a data monitoring committee | No |
| 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
|
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 8 |
| E.8.9.1 | In the Member State concerned days | 1 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 11 |
| E.8.9.2 | In all countries concerned by the trial days | 1 |
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