Clinical trial NCT06488664: An Efficacy and Safety Study of GNR-068 (Ustekinumab Biosimilar) and Stelara® in the Treatment of Patients With Moderate to Severe Plaque Psoriasis
Official title: Multicenter International Single-blind Randomized Comparative Clinical Study of the Efficacy and Safety of GNR-068 (45 mg) and Stelara® (45 mg) and Assessment of the Safety, Tolerability and Long-term Effectiveness of GNR-068 in Patients With Moderate and Severe Forms of Plaque Psoriasis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Plaque Psoriasis
Keywords: ustekinumab
humanized monoclonal antibodies
safety
plaque psoriasis
equivalence
biosimilar
PASI (Psoriasis Area and Severity Index)
BSA (Body Surface Area)
DLQI (Dermatological Life Quality Index)
PGA (Physician's Global Assessment)
immunogenicity
Lead sponsor: AO GENERIUM
Sponsor class: INDUSTRY
First posted: 2024-07-05
Enrollment: 422
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized single-blind comparative parallel group efficacy and safety study of ustekinumab biosimilar GNR-068 (45 mg) and reference product Stelara® (45 mg) in the treatment of patients with moderate and severe forms of plaque psoriasis. Participants received a subcutaneous dose of ustekinumab 45 mg (GNR-068 or Stelara®) at weeks 0 and 4 weeks then every 12 weeks thereafter until week 28 and then all patients receive GNR-068 45 mg. For patients with partially respond to the initial regimen the regimen can be adjusted.

Detailed description: The drug GNR-068 (INN: ustekinumab) is being developed as a biosimilar to the drug Stelara®, solution for subcutaneous administration (Silag AG, Switzerland).

Preclinical studies and early phase clinical studies suggest that interleukins-12 (IL-12) and -23 (IL-23), two molecules that are part of the communication network in the immune system, may play an important role in psoriasis. Ustekinumab is a monoclonal antibody directed against IL-12 and IL-23. This is a randomized, single blind, parallel-group, multicenter study to determine the effectiveness and safety of ustekinumab biosimilar GNR-068 administered subcutaneously as compared with Stelara® in patients with moderate to severe plaque-type psoriasis. Patients receive GNR-068 45 mg or Stelara 45 mg administered subcutaneously at weeks 0 and 4 weeks then every 12 weeks thereafter until week 28, thereafter until week 52 all patients receive GNR-068. For patients who partially respond to the initial regimen, the dose can be adjusted to 90 mg and then the interval can be adjusted to every 8 weeks. The study included a screening period, comparative treatment period, non-comparative treatment period, follow up period. Allocation of patients to treatment groups was carried out by randomization in a ratio of 1:1. 422 patients (211 to each study groups) were randomized.

Eligibility criteria: Inclusion Criteria:

* Written informed consent to participate in the study.
* Men and women 18-75 years of age, inclusive, at the time of signing the informed consent form.
* Patients diagnosed with plaque psoriasis at least 6 months before screening:

  1. Moderate or severe form of the disease, which is defined as: PASI index ≥12, body surface area (BSA) affected by plaque psoriasis, ≥10%, PGA scale score ≥3 (on a scale from 0 to 4).
  2. Presence of indications for systemic therapy, defined as inadequate control of the disease against the background of: local treatment (including local glucocorticosteroids) and/or phototherapy and/or lack of clinical effect from the use of other systemic methods.
  3. It is acceptable to carry out basic therapy for psoriatic arthritis at a stable dose for ≥ 4 weeks before screening: prednisolone at a dose of ≤10 mg per day, NSAIDs, methotrexate at a dose of ≤15 mg per week, sulfasalazine at a dose of 2.0 g per day.
* Body weight less than 100 kg.
* If it is necessary to take drugs that worsen the course of psoriasis (beta blockers, calcium channel blockers, lithium drugs, etc.): a stable dose of these drugs for ≥ 4 weeks before randomization.
* Consent of women of childbearing age, women in menopause lasting less than 2 years and male patients to comply with adequate methods of contraception throughout the study and for 3 months after the end of ustekinumab therapy.
* Patients should not be donors of blood or its components 30 days before inclusion in the study and not become donors of blood or its components throughout the study and for 3 months after its completion.

Exclusion Criteria:

* Types of psoriasis other than plaque, except for concomitant psoriatic arthritis.
* History of therapy with ustekinumab or any therapy aimed at IL-12 or IL-23 (briakinumab, guselkumab, tildrakizumab).
* Therapy with TNF-alpha inhibitors or any other genetically engineered biological drugs within 3 months before randomization.
* Conducting other systemic therapies (including cyclosporine, acitretin, methotrexate, UV and PUVA therapy) within 1 month before randomization.
* Treatment with leflunomide for 6 months before randomization.
* Spread of the inflammatory process involving the gastrointestinal tract (inflammatory bowel diseases), the organ of vision (uveitis, iridocyclitis), musculoskeletal structures (high activity of psoriatic arthritis, osteoarthritis, uncontrolled against the background of basic therapy (clause 3 Inclusion criteria) ).
* Major surgery (including joint surgery) within 8 weeks before the start of the study or elective surgery within 6 months after the start of the study.
* A history of an adverse drug reaction to any of the components of the study drug or a reference drug.
* Immunization with any live or live attenuated vaccine within 1 month before the first dose of the study drug or comparator drug.
* A history of a disease associated with the accumulation of immune complexes that may distort the assessment of the effectiveness of ustekinumab therapy (including serum sickness, systemic lupus erythematosus, rheumatoid arthritis, polymyositis, scleroderma, Sjogren's syndrome, vasculitis, cryoglobulinemia).
* Concomitant diseases and conditions that, in the opinion of the Investigator and/or Sponsor, jeopardize the safety of the patient during participation in the study, or which will influence the analysis of safety data.
* Active systemic infection (bacterial, viral or fungal) within 14 days before signing the informed consent.
* Pregnancy or breastfeeding.
* History of tuberculosis, positive/doubtful result of screening for tuberculosis infection (tuberculosis allergen test or IGRA test or fluorography results). Inclusion of such patients is possible if effective specific treatment for tuberculosis infection has been carried out and there is a conclusion from a phthisiatrician about the possibility of ustekinumab therapy.
* Participation in clinical trials of drugs less than 5 half-lives of the study drug before signing the informed consent.
* Positive test for hepatitis B or C, HIV or syphilis.
* Unwillingness or inability to comply with the recommendations prescribed by this protocol.
* Identification during screening of other diseases/conditions not listed above that, in the opinion of the physician-researcher, prevent the inclusion of the patient in the study.

Primary outcomes:
measure: The proportion of subjects with Psoriasis Area and Severity Index (PASI) Score of 75 Percent or Above
timeFrame: Week 12
Secondary outcomes:
measure: The proportion of patients achieving PASI50/75/90/100
timeFrame: Week 60
measure: Time to reach PASI50, PASI75, PASI90, PASI100
timeFrame: Week 60
measure: Area under the curve (AUC) of PASI
timeFrame: Week 60
measure: The proportion of partial responders (ie, patients achieving ≥50% but <75% improvement in PASI compared to baseline)
timeFrame: Week 60
measure: Changes in the BSA index
timeFrame: Week 60
measure: Changes in PGA
timeFrame: Week 60
measure: Changes in the intensity of itching on the visual analogue scale (VAS)
timeFrame: Week 60
measure: Changes in quality of life, assessed using the Dermatology Life Quality Index (DLQI)
timeFrame: Week 60
measure: The proportion of patients who dropped out of the study due to lack of sufficient therapeutic response
timeFrame: Week 60
Other outcomes:
Locations:
city: Murino
country: Russian Federation
facility: Limited Liability Company "Available Polyclinic"
state: Leningrad Region
city: Korolev
country: Russian Federation
facility: Limited Liability Company "Family Clinic No. 4"
state: Moscow Region
city: Kazan
country: Russian Federation
facility: Limited Liability Company Medical Center "Azbuka Health"
state: Republic Of Tatarstan
city: St. Petersburg
country: Russian Federation
facility: Limited Liability Company "Clinic of Skin Diseases Pierre Wolkenstein"
state: Saint Petersburg
city: St. Petersburg
country: Russian Federation
facility: Limited Liability Company "International Medical Center"
state: Saint Petersburg
city: St. Petersburg
country: Russian Federation
facility: Limited Liability Company "Health Energy"
state: Saint Petersburg
city: St. Petersburg
country: Russian Federation
facility: Limited Liability Company "Institute of Medical Research"
state: Saint Petersburg
city: St. Petersburg
country: Russian Federation
facility: Limited Liability Company "PiterKlinika"
state: Saint Petersburg
city: St. Petersburg
country: Russian Federation
facility: Private medical institution "Euromedservice"
state: Saint Petersburg
city: St. Petersburg
country: Russian Federation
facility: Limited Liability Company "MEDINET"
state: Saint Petersburg
city: Barnaul
country: Russian Federation
facility: Federal State Budgetary Educational Institution of Higher Education "Altai State Medical University" of the Ministry of Health of the Russian Federation
city: Chelyabinsk
country: Russian Federation
facility: State budgetary healthcare institution "Chelyabinsk Regional Clinical Dermatovenerological Dispensary"
city: Chelyabinsk
country: Russian Federation
facility: Limited Liability Company "Ecology of Health"
city: Ekaterinburg
country: Russian Federation
facility: State budgetary institution of the Sverdlovsk region "Ural Research Institute of Dermatovenereology and Immunopathology"
city: Izhevsk
country: Russian Federation
facility: Limited Liability Company "Alliance Biomedical - Ural Group"
city: Kirov
country: Russian Federation
facility: Federal State Budgetary Educational Institution of Higher Education "Kirov State Medical University" of the Ministry of Health of the Russian Federation (FSBEI HE Kirov State Medical University of the Ministry of Health of Russia))
city: Lipetsk
country: Russian Federation
facility: State health care institution "Regional Dermatovenerological Dispensary"
city: Moscow
country: Russian Federation
facility: Limited Liability Company "OLLA-MED"
city: Moscow
country: Russian Federation
facility: Federal State Budgetary Institution "Research Institute of Rheumatology named after V.A. Nasonova"
city: Moscow
country: Russian Federation
facility: Limited Liability Company "Firma ORIS"
city: Moscow
country: Russian Federation
facility: State budgetary healthcare institution of the city of Moscow "Moscow Scientific and Practical Center of Dermatovenereology and Cosmetology of the Moscow Health Department"
city: Moscow
country: Russian Federation
facility: Federal State Budgetary Educational Institution of Higher Education "Russian University of Medicine" of the Ministry of Health of the Russian Federation (FSBEI HE "Russian University of Medicine" of the Ministry of Health of Russia)
city: Moscow
country: Russian Federation
facility: State budgetary healthcare institution of the Moscow region "Moscow Regional Research Clinical Institute named after M.F. Vladimirsky"
city: Novosibirsk
country: Russian Federation
facility: Limited Liability Company "Medical Center "Healthy Family"
city: Orenburg
country: Russian Federation
facility: Federal State Budgetary Educational Institution of Higher Education Orenburg State Medical University of the Ministry of Health of Russia
city: Ryazan
country: Russian Federation
facility: State budgetary institution of the Ryazan region "Regional clinical dermatovenerological dispensary"
city: Saint Petersburg
country: Russian Federation
facility: Limited Liability Company "Medical Technologies" LLC "Medical Technologies"
city: Saint Petersburg
country: Russian Federation
facility: Limited Liability Company "Interleukin"
city: Saint Petersburg
country: Russian Federation
facility: Limited Liability Company "Research Center Eco-Safety"
city: Saint Petersburg
country: Russian Federation
facility: Limited Liability Company "ArsVite North-West"
city: Saint Petersburg
country: Russian Federation
facility: Limited Liability Company "Curator"
city: Saratov
country: Russian Federation
facility: Limited Liability Company "SB Clinic of Cosmetology"
city: Smolensk
country: Russian Federation
facility: Regional state budgetary healthcare institution "Smolensk Dermatovenerological Dispensary"
city: Ulyanovsk
country: Russian Federation
facility: State Budgetary Healthcare Institution Ulyanovsk area Clinical Hospital
Study officials:
affiliation: JSC GENERIUM
name: Oksana A. Markova, MD
role: STUDY_CHAIR
References: