A Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy, Safety, Pharmacokinetics, and Immunogenicity of Netakimab in Children With Moderate to Severe Plaque Psoriasis
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- Biocad
- 入组人数
- 140
- 试验地点
- 28
- 主要终点
- Proportion of subjects achieving PASI75
研究概览
简要总结
The aim of the study is to evaluate the efficacy and safety of netakimab compared with placebo in a pediatric population of subjects over 6 years of age with moderate to severe plaque psoriasis. The study will have randomized, double-blind, placebo-controlled study with open-arm comparison.
详细描述
Following screening, subjects will be randomized to receive either netakimab, placebo or adalimumab and enter the main study period.
During the main study period, subjects will receive therapy with netakimab/placebo (double-blind arms) or adalimumab (open-label arm), which will be administered subcutaneously until week 12.
At Week 12, after completion of all scheduled procedures subjects in groups netakimab/placebo will continue to receive open-label netakimab for up to week 58, subjects in group adalimumab will switch to open-label adalimumab after 8-week "washout" period.
At Week 58, after completion of all scheduled procedures subjects with sPGA ≤1 will be re-randomised to recieve either netakimab or placebo in double-blind maner. The subjects with >1 will continue to recieve open-label netakimab.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 6 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent of the legal representative and the subject to participate in the study (the study subject signs the appendix to the information sheet for the legal representative of the clinical study subject with informed consent form).
- •For Stage 1 only: age ≥12 and <18 years at the time of randomization.
- •For Stage 2 only: age ≥6 and <12 years at the time of randomization.
- •A diagnosis of moderate to severe plaque psoriasis with a disease duration of the disease being at least 3 months before the signing of the ICF.
- •Subjects who are candidates for phototherapy or systemic therapy for psoriasis (including non-responders to systemic therapy or phototherapy), in the opinion of the Investigator, or who did not achieve adequate disease control with topical agents.
- •At the time of the screening examination, the body surface area affected by psoriasis is >10% of the body surface area (BSA), the Psoriasis Area and Severity Index (PASI) score is ≥12, and the static Physician's Global Assessment (sPGA) score is ≥
- •Subjects with the normal laboratory test results at screening.
- •Subjects with a negative whole blood IFN-γ release test.
- •The ability of the subject and his/her legal representative, in the Investigator's opinion, to perceive information and follow the Protocol procedures.
- •Willingness of subjects and their sexual partners of childbearing potential to use highly effective methods of contraception from the signing of the ICF to 12 weeks after the last dose of the investigational product. This requirement does not apply to subjects who have not reached sexual maturity or who have undergone surgical sterilization. The subject's legal representative must consent to the subject's use of contraception.
排除标准
- •1. Erythrodermic, pustular, guttate psoriasis, drug-induced psoriasis or any other skin diseases (e.g. eczema) at screening that can affect/complicate the assessment of psoriasis treatment with the investigational product.
- •2. Use of the following medications:
- •Prior use of drugs based on monoclonal antibodies against interleukin-17 or its receptor.
- •Prior use of adalimumab.
- •Prior use of monoclonal antibodies or their fragments within 12 weeks before signing the ICF.
- •Use of systemic non-biological medicinal products including methotrexate, sulfasalazine, cyclosporine or acitretin within 4 weeks prior to the date of signing the ICF. If previously used systemic non-biologic drugs are discontinued for any reason, the screening period can be extended for up to 8 calendar weeks, during which new systemic non-biologic drugs are not prescribed.
- •Use of phototherapy (including selective phototherapy [UV-B] and photochemotherapy [PUVA]) less than 4 weeks before the date of signing the ICF.
- •Vaccination with live vaccines at any time within 12 weeks prior to signing the ICF or an expected need for such vaccination during the study.
- •3. Recurrent, chronic, or any other active infection in which, in the opinion of the Investigator, the investigational product may harm the study subject.
- •4. Sepsis or risk of sepsis.
- •Positive HIV-1 or HIV-2 test.
- •HBV/HCV infections (for details, see Section 6.5.7.2).
- •Established diagnosis or a history of immunodeficiency syndrome (e.g., severe combined immunodeficiency syndrome, T and B cell deficiency syndromes, chronic granulomatous disease), or an infection characteristic of an immunodeficiency (e.g., pneumocystis pneumonia, histoplasmosis or coccidioidomycosis) at the time of signing the ICF.
- •8. Diagnosis of tuberculosis, including a history of tuberculosis.
- •A clinically significant infection caused by the varicella-zoster virus within 12 weeks prior to signing the ICF.
- •10. Body temperature ≥38°C at the screening. These subjects may be re-screened, but not earlier than 4 weeks after the first screening.
- •11. Other concomitant medical conditions that continued at the time of the screening examination, which increase the risk of adverse events during the study or may affect the evaluation of psoriasis symptoms, mask, enhance, or alter the symptoms of psoriasis, or cause clinical or laboratory symptoms similar to those of psoriasis and confirmed by the source documentation:
- •Active inflammatory diseases or aggravation of chronic inflammatory diseases other than psoriasis.
- •Functional class III-IV stable angina of effort, unstable angina or a history of myocardial infarction within 1 year before signing the IC.
- •Moderate to severe cardiac failure (NYHA class III-IV).
- •Grade 2 hypertension.
- •A history of atopic asthma, angioedema.
- •Moderate to severe respiratory failure, Grade 3/4 chronic obstructive pulmonary disease.
- •Decompensated diabetes mellitus; decompensated hypothyroidism, decompensated thyrotoxicosis.
- •Significant systemic autoimmune diseases according to the Investigator.
- •A history of Crohn's disease, ulcerative colitis.
- •Any other underlying conditions (including but not limited to metabolism, hematology, renal, hepatic, pulmonary, neurological, endocrine, cardiac, and gastrointestinal disorders; infections) that may, in the Investigator's opinion, affect the course of psoriasis, affect the assessment of its symptoms, or put the subject using the study therapy at unacceptable risk.
- •12. Malignant and lymphoproliferative diseases, including lymphoma; symptoms indicating the development of a lymphoproliferative disease (such as lymphadenopathy and/or splenomegaly), except for those previously excluded by a biopsy.
- •13. History of allergic reactions (anaphylactic shock or allergy to 2 or more drugs).
- •14. Known allergy or intolerance to monoclonal antibody products or any components of the investigational product.
- •15. Major surgery within 30 days before the screening, or a major surgery scheduled at any time during the study.
- •16. Severe infections (including those that required hospitalization or parenteral antibacterial, antimycotic, or antiprotozoal agents) within 6 months prior to signing the ICF.
- •17. Use of systemic antibacterial, antimycotic, or antiprotozoal agents within 2 months before signing the ICF.
- •18. More than 4 episodes of respiratory infections over the past 6 months prior to signing the ICF.
- •19. Any concomitant diseases in which, in the Investigator's opinion, the study therapy may harm the subject.
- •20. Signs of premature puberty at the screening examination.
- •Pregnancy, breastfeeding, or planning pregnancy while participating in the study.
- •22. Any psychiatric disorder, including a history of severe depressive disorders and/or suicidal thoughts, which, in the opinion of the Investigator, may pose an excessive risk to the subject or affect the subject's ability to follow the Protocol.
- •23. Drug addiction, alcoholism, or abuse with drugs or other psychoactive substances (including a history of such disorders).
- •24. Simultaneous participation in other clinical studies, as well as previous participation in other clinical studies less than 3 months before signing the ICF, prior participation in this study.
- •25. Use of any other investigational products at the time of signing the ICF or less than 28 days before the planned date of signing the ICF or 5 half-lives (whichever is longer) before the date of signing the ICF.
研究组 & 干预措施
PBO
placebo given subcutaneously during main period and treatment discontinuation period
干预措施: Placebo (Drug)
ADA
adalimumab given subcutaneously during main period
干预措施: Adalimumab (Drug)
NTK
netakimab given subcutaneously during main period, open-label period and treatment discontinuation period
干预措施: Netakimab (Drug)
结局指标
主要结局
Proportion of subjects achieving PASI75
时间窗: Week 12
PASI combines assessments of the extent of body surface involvement in 4 regions (head \& neck(h), trunk(t), arms(u), legs(l)) \& severity of scaling (S), redness (R), \& plaque induration/infiltration (thickness, T) in each region. Severity is rated for each index (R, S, T) on a 0-4 scale (0 for no involvement up to 4 for severe involvement): 0 = none, 1 = slight, 2 = mild, 3 = moderate, 4 = severe Fraction of total body surface area (BSA) affected is graded on a 0-6 scale (0 for no involvement to 6 for 90% - 100% involvement): 0 = 0% (clear), 1 = \>0% to \<10%, 2 = 10% to \<30%, 3 = 30% to \<50%, 4 = 50% to \<70%, 5 = 70% to 90%, 6 = 90% to 100%. Overall score ranges from 0 (no psoriasis) to 72 (most severe disease).
Proportion of subjects achieving sPGA0/1
时间窗: Week 12
Static Physician Global Assessment (sPGA): The physician's global assessment of the Participant's psoriasis lesions at a given time point. Plaques are assessed for induration, erythema, and scaling, and an overall rating of psoriasis severity is given using the anchors of clear (0), minimal (1), mild (2), moderate (3), severe (4), or very severe (5). An sPGA assessed as either 0 or 1 represents a clinically meaningful response of minimal plaque severity or complete resolution of plaque psoriasis.
次要结局
- Proportion of subjects achieving PASI75(Week 58, Week 102)
- Pharmacokinetics assessment(Through Week 102)
- Proportion of subjects achieving sPGA0/1(Week 58, Week 102)
- Proportion of subjects achieving IGA mod 2011 0/1(Week 12, Week 58, Week 102)
- Proportion of subjects achieving PASI90(Week 12, Week 58, Week 102)
- Proportion of subjects achieving PASI100(Week 12, Week 58, Week 102)
- Proportion of subjects achieving sPGA0(Week 12, Week 58, Week 102)
- Mean change in the PASI score from baseline(Week 12, Week 58, Week 102)
- Mean change in the Nail Psoriasis Severity Index NAPSI from baseline (for subjects with NAPSI>0 at baseline)(Week 12, Week 58, Week 102)
- Mean change in the pruritus severity score on the numerical rating scale (NRS) from baseline.(Week 12, Week 58, Week 102)
- Time to relapse defined as sPGA≥2 during the treatment discontinuation period(Week 58 through Week 102)
- Safety assessment(Through Week 124)
- Immunogenicity assessment(Through Week 102)