| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Active Psoriatic Arthritis | |
| E.1.1.1 | Medical condition in easily understood language | | Chronic, inflammatory disease of the joints and the places where tendons and ligaments connect to bone. | |
| E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.0 | | E.1.2 | Level | LLT | | E.1.2 | Classification code | 10037160 | | E.1.2 | Term | Psoriatic arthritis | | E.1.2 | System Organ Class | 100000004859 | |
| 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 evaluate the efficacy of 3 different dose regimens of sonelokimab (120 mg once every 2 weeks [Q2W], 60 mg Q2W, and 60 mg once every 4 weeks [Q4W]) compared with placebo in the treatment of participants with active psoriatic arthritis (PsA). | |
| E.2.2 | Secondary objectives of the trial | 1. To evaluate the safety and tolerability of 3 different dose regimens of sonelokimab (120 mg Q2W, 60 mg Q2W, and 60 mg Q4W) compared with placebo in the treatment of participants with active PsA;
2. To assess the pharmacokinetics (PK) and immunogenicity of 3 different dose regimens of sonelokimab (120 mg Q2W, 60 mg Q2W, and 60 mg Q4W) in the treatment of participants with active PsA. | |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria | 1. Participant is ≥18 years of age;
2. Participant has a confirmed diagnosis of PsA per the 2006 ClASsification criteria for Psoriatic ARthritis (CASPAR) with symptoms for ≥6 months prior to the Screening Visit;
3. Participant has active disease (defined by a TJC68 of ≥3 and a SJC66 of ≥3);
4. Participant has either current active PsO or a history of PsO; in either case, this diagnosis must have been confirmed by a dermatologist;
5. Participant tests negative for rheumatoid factor (RF) at the Screening Visit;
6. Participant tests negative for anti-cyclic citrullinated peptide (CCP) antibodies at the Screening Visit;
7. Participant must be, in the opinion of the investigator at both the Screening Visit and study treatment initiation, a suitable candidate for treatment with adalimumab per approved local product information. If a chest X-ray or computer tomography (CT) scan for tuberculosis (TB) screening is required per local guidance, the X-ray or CT scan must be taken within 3 months prior to the Screening Visit;
8. Participant has had an inadequate response at the Screening Visit (lack of efficacy after ≥12-week duration of therapy) to previous or current treatment with ≥1 non-biologic disease-modifying anti-rheumatic drug (DMARD) at maximally tolerated dose, or participant has an intolerance to or contraindication for DMARDs as defined by the investigator;
9. If the participant is female, she must be of non-childbearing potential or – if of childbearing potential, participant must agree to use highly effective methods of contraception.
10. Women of childbearing potential must have a negative serum human chorionic gonadotropin (hCG) pregnancy test at the Screening Visit and a negative urine pregnancy test at Week 0/Day 1 prior to the first administration of study treatment;
11. If male, participant must be willing to use a condom when sexually active with a partner of childbearing potential during the study and for 12 weeks after the last dose of study treatment, unless surgically sterile;
12. Participant is considered reliable and capable of adhering to the protocol, visit schedule, or medication intake according to the judgment of the investigator;
13. Participant is able to understand and provide signed informed consent. | |
| E.4 | Principal exclusion criteria | 1. Known hypersensitivity to sonelokimab, adalimumab or any of its excipients;
2. Subjects who currently uses or plans to use 1 or more prohibited treatments specified in this protocol. Prohibited treatments and washout periods detailed in the protocol must be adhered to;
3. Subjects who has previously failed on anti (IL)-17 therapy, after at least 16 weeks of treatment; or is unsuitable for anti-IL-17 therapy for any reason according to the investigator’s discretion;
4. Subjects who has previously failed on anti-tumor necrosis factor alpha (TNFα) therapy, after at least 16 weeks of treatment; or is unsuitable for anti-TNFα therapy for any other reason according to the investigator’s discretion;
5. Subjects who has had previous exposure to more than 2 biologic agents of any type to treat PsA prior to the Screening Visit, including but not limited to IL-17 inhibitors, IL-23 inhibitors, TNFα inhibitors, etc;
6. Subjects who has a diagnosis of chronic inflammatory conditions other than PsO or PsA, including but not limited to rheumatoid arthritis (RA), sarcoidosis, systemic lupus erythematosus, Crohn’s disease, or ulcerative colitis;
7. Has a diagnosis of arthritis mutilans;
8. Has an active infection or history of infections, as defined in the protocol;
9. Subjects who received a live (including attenuated) vaccination within 8 weeks before study treatment initiation, or planned to receive a live vaccination during the study and up to at least 12 weeks after the last dose of study treatment. Examples of restricted vaccinations provided in the protocol;
10. Subjects who received a Bacillus Calmette-Guérin (BCG) vaccination within 1 year before study treatment initiation;
11. Participant with:
a. A history of active tuberculosis (TB).
b. Evidence of TB infection, unless the criteria as defined by the protocol apply.
12. Any current nontuberculous mycobacterial (NTM) infection or any history of pulmonary NTM infection at the Screening Visit;
13. Evidence of acute ocular inflammation, including active anterior uveitis (i.e., acute episode), within the last 4 weeks before study treatment initiation;
14. Concurrent malignancy or a history of malignancy during the past 5 years of the Screening Visit, exceptions providing in the protocol;
15. Subjects with fibromyalgia, osteoarthritis symptoms, or any other condition that in the investigator’s opinion may potentially interfere with efficacy assessments;
16. Subjects with erythrodermic, guttate, or pustular form of PsO or drug-induced PsO;
17. History of a lymphoproliferative disorders, including lymphoma, or current signs and symptoms suggestive of lymphoproliferative disease;
18. Primary immunodeficiencies, prior splenectomy, or suppressive conditions, including participants taking immunosuppressive therapy following organ transplants;
19. Had major surgery (including joint surgery) within 6 months, or is planning to have major surgery during the study;
20. Presence of active suicidal ideation, or positive suicidal behaviour, shows any history of suicidal attempt (including an actual attempt, interrupted attempt, or aborted attempt), or suicidal ideation in the past 6 months;
21. Subjects has presence of moderately severe depression or severe depression, indicated by a score of ≥15 using the screening PHQ-9. Subjects are permitted to use 1 medication to treat depression provided dose is stable for 4 weeks prior to initiation of study treatment. Subjects on multiple medications for depression are excluded from the study;
22. Severe cardiovascular comorbidities including history of myocardial infarction, unstable angina pectoris, stroke, heart failure, or uncontrolled hypertension;
23. Clinically significant ECG abnormalities on centrally read ECG at the Screening Visit;
24. Any other clinically significant medical conditions or any other reason, including any physical, psychological, or psychiatric condition, that would compromise the safety or interfere with participation in the study, would make the subjects an unsuitable candidate to receive study treatment, or would put the subjects at risk;
25. Subjects with laboratory abnormalities at the Screening Visit, as defined by the protocol;
26. Subjects is enrolled in another interventional investigational device or drug study, or has been in another investigational device or drug study in the last 28 days or within 5 half-lives of the investigational study treatment prior to the Screening Visit, whichever is greater;
27. Subjects is pregnant or breastfeeding, or plans to become pregnant while enrolled in the study and up to 12 weeks after the last dose of study treatment;
28. History of chronic alcohol or drug abuse in the past year prior to the Screening Visit;
29. Subjects is an employee, or direct relative of an employee, of the sponsor, at a study site, or of a third-party organization involved in the study. | |
| E.5 End points |
| E.5.1 | Primary end point(s) | | Response rate of at least 50% improvement in the American College of Rheumatology (ACR50) response criteria at Week 12 compared with baseline. | |
| E.5.1.1 | Timepoint(s) of evaluation of this end point | | From Baseline to week 12. | |
| E.5.2 | Secondary end point(s) | 1. ACR20 response rate at Week 12 compared with baseline;
2. Psoriasis Area and Severity Index (PASI) 100 at Week 12 (in the subgroup of participants with psoriasis [PsO] involving at least 3% body surface area [BSA] at baseline). | |
| E.5.2.1 | Timepoint(s) of evaluation of this end point | From Baseline to week 12.
| |
| 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 | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| 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 | |
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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 | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 5 |
| E.8.3 | The trial involves single site in the Member State concerned | Information not present in EudraCT |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 51 |
| 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 | | United States | | Poland | | Bulgaria | | Spain | | Czechia | | Germany | | Hungary | |
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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 | |
| 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 | 10 |
| E.8.9.1 | In the Member State concerned days | |
| 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 | 10 |
