An Efficacy and Safety Study of GNR-068 (Ustekinumab Biosimilar) and Stelara® in the Treatment of Patients With Moderate to Severe Plaque Psoriasis

Phase 3

Active, not recruiting

• Conditions: Plaque Psoriasis

• Registration Number: NCT06488664
• Lead Sponsor: AO GENERIUM

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.

Study Timeline

• Study Start: 2023-07-25
• Status Verified: 2024-06
• Study First Submitted: 2024-06-28
• Study First Submitted QC: 2024-07-03
• Last Update Submitted: 2024-07-03
• Study First Posted: 2024-07-05
• Last Update Posted: 2024-07-05
• Primary Completion: 2024-12-20
• Study Completion: 2025-03-20

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 422

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
The proportion of subjects with Psoriasis Area and Severity Index (PASI) Score of 75 Percent or Above	Week 12	PASI is a widely used tool for the measurement of severity of psoriasis. This is a test of how bad a person's psoriasis is. The scale combines redness, scaling, and thickness, as well as overall body involvement to determine the PASI score. The scale ranges from 0 (best) to 72 (worst).

Secondary Outcome Measures

Name	Time	Method
Area under the curve (AUC) of PASI	Week 60	PASI is a widely used tool for the measurement of severity of psoriasis. This is a test of how bad a person's psoriasis is. The scale combines redness, scaling, and thickness, as well as overall body involvement to determine the PASI score. The scale ranges from 0 (best) to 72 (worst).
The proportion of patients achieving PASI50/75/90/100	Week 60	PASI is a widely used tool for the measurement of severity of psoriasis. This is a test of how bad a person's psoriasis is. The scale combines redness, scaling, and thickness, as well as overall body involvement to determine the PASI score. The scale ranges from 0 (best) to 72 (worst).
The proportion of partial responders (ie, patients achieving ≥50% but <75% improvement in PASI compared to baseline)	Week 60	PASI is a widely used tool for the measurement of severity of psoriasis. This is a test of how bad a person's psoriasis is. The scale combines redness, scaling, and thickness, as well as overall body involvement to determine the PASI score. The scale ranges from 0 (best) to 72 (worst).
Changes in PGA	Week 60	The PGA is 7-point scale used in clinical trials of various diseases. In this the physician checks the state of the disease and gives them score from 0 (clear) to 5 (severe).
Changes in the intensity of itching on the visual analogue scale (VAS)	Week 60	The intensity of itching is carried out at all visits using a visual analogue scale (VAS), where the left end of the line is 0 = no itching, the right end of the line is 10 = intense itching
The proportion of patients who dropped out of the study due to lack of sufficient therapeutic response	Week 60	Treatment failure is assessed as no effect within 28 weeks (PASI response \<50%)
Time to reach PASI50, PASI75, PASI90, PASI100	Week 60	PASI is a widely used tool for the measurement of severity of psoriasis. This is a test of how bad a person's psoriasis is. The scale combines redness, scaling, and thickness, as well as overall body involvement to determine the PASI score. The scale ranges from 0 (best) to 72 (worst).
Changes in the BSA index	Week 60	Using the BSA (Body Surface Area) index, the surface area of the skin affected by psoriasis is assessed. BSA is measured in %. To determine the area of psoriatic skin lesions the "palm" rule is applicable. On the scalp, the affected area the size of one palm is assumed to be 10%, the torso - 3.3%, the upper extremities - 5%, the lower extremities - 2.5% of the area of the anatomical region of the body. To calculate the total BSA, each reported percentage must be multiplied by the corresponding factor of the corresponding body region (head = 0.1, torso = 0.3, upper extremities = 0.2, lower extremities = 0.4). The resulting four percentage values (percentage of skin affected by psoriasis on the scalp, upper extremities, trunk, and lower extremities) will be summed to estimate the BSA index.
Changes in quality of life, assessed using the Dermatology Life Quality Index (DLQI)	Week 60	The DLQI is a 10-item questionnaire, that in addition to evaluating overall quality of life, can be used to assess 6 different aspects that may affect quality of life: symptoms and feelings, daily activities, leisure, work or school performance, personal relationships, and treatment. Scores range from 0 (no impairment in quality of life) to 30 (most impairment in quality of life).

Trial Locations

Locations (34)

Limited Liability Company "Available Polyclinic"; 🇷🇺 Murino, Leningrad Region, Russian Federation

Limited Liability Company "Family Clinic No. 4"; 🇷🇺 Korolev, Moscow Region, Russian Federation

Limited Liability Company Medical Center "Azbuka Health"; 🇷🇺 Kazan, Republic Of Tatarstan, Russian Federation

Limited Liability Company "Clinic of Skin Diseases Pierre Wolkenstein"; 🇷🇺 St. Petersburg, Saint Petersburg, Russian Federation

Limited Liability Company "International Medical Center"; 🇷🇺 St. Petersburg, Saint Petersburg, Russian Federation

Limited Liability Company "Health Energy"; 🇷🇺 St. Petersburg, Saint Petersburg, Russian Federation

Limited Liability Company "Institute of Medical Research"; 🇷🇺 St. Petersburg, Saint Petersburg, Russian Federation

Limited Liability Company "PiterKlinika"; 🇷🇺 St. Petersburg, Saint Petersburg, Russian Federation

Private medical institution "Euromedservice"; 🇷🇺 St. Petersburg, Saint Petersburg, Russian Federation

Limited Liability Company "MEDINET"; 🇷🇺 St. Petersburg, Saint Petersburg, Russian Federation

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