Study of the Efficacy, Safety, Pharmacokinetics, and Immu... | NCT06640517

Label	Type	Description	Intervention Names
NTK	Experimental	netakimab given subcutaneously during main period, open-label period and treatment discontinuation period	Drug: Netakimab
PBO	Placebo Comparator	placebo given subcutaneously during main period and treatment discontinuation period	Drug: Placebo
ADA	Active Comparator	adalimumab given subcutaneously during main period	Drug: Adalimumab

Name	Type	Description	Arm Group Labels	Other Names
Netakimab	Drug	netakimab will be administered subcutaneously with induction once a week for the first three weeks, then once every 4 weeks	NTK

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Proportion of subjects achieving PASI75	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).	Week 12
Proportion of subjects achieving sPGA0/1	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.	Week 12

Secondary Outcomes

Measure	Description	Time Frame
Proportion of subjects achieving PASI75	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 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).

Other Outcomes

Measure	Description	Time Frame
Mean change in the PSSI score from baseline (for subjects with PSSI>0 at baseline)	The scalp is assessed for erythema (redness), induration (hardness), and desquamation (shedding of skin) and percentage of area affected as follows: Erythema, Induration and Desquamation: 0 = Absent = Slight = Moderate = Severe = Severest Possible Percent of Scalp Involved: <10% 10% - 29% 30% - 49% 50% - 69% 70% - 89% 90% - 100% The PSSI score is a composite score derived from the sum of the scores for erythema, induration and desquamation multiplied by the score for the extent of scalp area involved (percent of scalp involved). The range is 0 (no psoriasis) to 72 (Most severe Disease).

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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 ≥3.
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.

Exclusion Criteria:

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. 5. Positive HIV-1 or HIV-2 test. 6. HBV/HCV infections (for details, see Section 6.5.7.2). 7. 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. 9. 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. 21. 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.

ID	Term
C000718740	netakimab
D000068879	Adalimumab

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins