Efficacy and Safety of Subcutaneous Sonelokimab Versus Placebo and Risankizumab in Adults with Active Psoriatic Arthritis and Inadequate Response to TNF-α Inhibitors
- Trial ID
- 2024-516219-25-00
- Protocol
- M1095-PSA-302
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** of sonelokimab at doses of 60 mg and 120 mg compared to placebo in participants with active **psoriatic arthritis** (PsA) at Week 16, using the ACR50 response criteria. This is clinically relevant as achieving an ACR50 response indicates a significant improvement in joint symptoms, which is crucial for enhancing the quality of life in patients with PsA.
Secondary objectives include:
- Evaluating the efficacy of sonelokimab 60 mg and 120 mg at Week 16 compared with placebo in participants with active PsA.
- Assessing the efficacy of sonelokimab 60 mg and 120 mg at Week 16 compared with risankizumab in participants with active PsA.
- Evaluating the safety and tolerability of sonelokimab 60 mg and 120 mg over time in the treatment of participants with active PsA.
Participants
The clinical trial involves a total of **228 participants** diagnosed with **psoriatic arthritis**. The study population includes both male and female subjects, aged **18 years and older**, who have been confirmed to meet the 2006 Classification for Psoriatic Arthritis (CASPAR) criteria. Participants are required to have moderate to severe active disease and must have been on a stable dose of NSAIDs for at least four weeks prior to screening, with inadequate symptom control, or have a documented intolerance or contraindication to at least one NSAID. The trial population was selected based on their ability to adhere to the protocol and their suitability for treatment with risankizumab, as determined by the investigator. Participants must have experienced an inadequate response to one or two TNFα inhibitors or have discontinued treatment due to safety or tolerability issues. Both male and female participants are required to use effective contraception methods during the study and for a specified period after the last dose of the study treatment. The trial does not exclude vulnerable populations, and the participants are expected to maintain compliance with the study requirements throughout the trial duration.
Plans and Procedures
The clinical trial is a **Phase 3**, parallel-group, randomized, double-blind, 4-arm, placebo-controlled, multicenter study designed to evaluate the efficacy and safety of subcutaneous **sonelokimab** in participants with active **psoriatic arthritis**. The trial includes an active reference arm with **risankizumab**. The study targets male and female participants aged 18 years and older who have shown an inadequate response or intolerance to tumor necrosis factor-α inhibitors. The primary objective is to assess the efficacy of sonelokimab at doses of 60 mg and 120 mg compared to placebo, using the ACR50 response criteria at Week 16. The trial is expected to conclude by December 2026, with recruitment starting in May 2025.
Participants will be randomly assigned to one of four arms: two arms receiving sonelokimab at different dosages, one arm receiving risankizumab as an active comparator, and one arm receiving a placebo. The trial will be conducted over a maximum treatment period of 48 weeks for sonelokimab and 40 weeks for risankizumab. The study involves several visits, starting with a screening visit to confirm eligibility based on criteria such as age, diagnosis of psoriatic arthritis, and previous treatment history. Follow-up visits will occur at regular intervals to monitor efficacy and safety outcomes, including the assessment of ACR response criteria, minimal disease activity, and changes in health assessment questionnaires. The end-of-study visit will evaluate the overall outcomes and any adverse events experienced by participants.
Participant involvement is expected to last for the duration of the treatment period, with additional follow-up as required by the study protocol. Conditions that may lead to early termination from the study include non-compliance with the study protocol, withdrawal of consent, or the occurrence of adverse events that necessitate discontinuation of the study drug. The trial is structured to ensure rigorous monitoring and data collection to support the evaluation of the investigational product's efficacy and safety in the target population.
Treatment
The clinical trial involves the administration of **Sonelokimab**, an experimental medication developed by Moonlake Immunotherapeutics AG. Sonelokimab is a **nanobody** that inhibits IL-17A and IL-17F, and is provided in the form of an **injection**. The medication is administered via **subcutaneous injection**. Two dosing regimens are employed in the study: 60 mg and 120 mg, with a maximum daily dose of 60 mg and 120 mg, respectively. The total maximum dose for the 60 mg regimen is 900 mg, while for the 120 mg regimen, it is 1800 mg. The treatment period extends up to 48 weeks. Compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol.
**Skyrizi** (risankizumab) serves as the active comparator in this study. Manufactured by AbbVie Deutschland GmbH & Co. KG, Skyrizi is a **solution for injection** provided in a pre-filled syringe. It is also administered via **subcutaneous injection**. The dosage for Skyrizi is 150 mg, with a maximum total dose of 750 mg over a treatment period of 40 weeks. The administration and dosing schedule for Skyrizi are designed to align with standard clinical practices for its use in treating conditions similar to those being studied in this trial.
A **placebo** is utilized as a control in this trial. The placebo is a sterile solution provided in a single-use prefilled syringe intended for **subcutaneous administration**. The placebo is designed to mimic the administration of the active treatments without containing any active pharmaceutical ingredients. This allows for the assessment of the efficacy and safety of Sonelokimab by providing a baseline for comparison.
Efficacy
The efficacy of **sonelokimab** in the treatment of active psoriatic arthritis will be assessed in a Phase 3, randomized, double-blind, placebo-controlled clinical trial. The primary endpoint for evaluating efficacy is the proportion of participants achieving an ACR50 response, which indicates a 50% improvement according to the American College of Rheumatology (ACR) response criteria, at Week 16. Secondary endpoints include the proportion of participants achieving ACR20 (20% improvement) and Minimal Disease Activity (MDA) at Week 16, as well as changes from baseline in the Health Assessment Questionnaire—Disability Index (HAQ-DI) and the SF-36 Physical Component Summary (PCS) at Week 16. Additionally, the proportion of participants achieving a PASI90 response, indicating a 90% improvement in the Psoriasis Area and Severity Index, will be evaluated in a subset of participants with psoriasis involving at least 3% of body surface area at baseline.
Efficacy assessments will be conducted at specified timepoints, with the primary and secondary endpoints measured at Week 16. The ACR response criteria, HAQ-DI, and SF-36 PCS are validated scales used to quantify symptom improvement and quality of life changes. The trial will also monitor the incidence, relatedness, severity, and seriousness of treatment-emergent adverse events (TEAEs), as well as any clinically relevant abnormalities in vital signs, 12-lead ECG variables, and laboratory parameters. These assessments will provide a comprehensive evaluation of the efficacy and safety of sonelokimab in comparison to placebo and the active reference arm, risankizumab.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Participants must be ≥18 years of age at the time of signing the informed consent.
- Participants who have a confirmed diagnosis of PsA per the 2006 Classification for Psoriatic Arthritis (CASPAR) criteria with symptoms for ≥6 months before the Screening Visit.
- Participants who have moderate to severe active disease (defined by a TJC68 of ≥3 and a SJC66 of ≥3).
- Participants who have current active plaque PsO with ≥1 psoriatic plaque of ≥2 cm or nail changes consistent with PsO or a dermatologist-confirmed personal history of plaque PsO.
- Participants who are, in the opinion of the investigator, a suitable candidate for treatment with risankizumab per approved prescribing information, and agrees to maintain compliance with the approved prescribing information throughout study participation.
- Participants who test negative for both rheumatoid factor and anti-cyclic citrullinated peptide at the Screening Visit.
- Participants should have been taking a stable dose of NSAIDs for a period of ≥4 weeks before screening, with inadequate control of symptoms, or should have a documented intolerance or contraindication to ≥1 NSAID.
- Participants must have received one or more biologic TNFα inhibitors for PsA or PsO and must have experienced an inadequate response to treatment with at least one TNFα inhibitor given at an approved dose for PsA for ≥3 months, or have stopped treatment due to safety/tolerability problems after ≥1 administration of a TNFα inhibitor. Note: the washout requirements for TNFα inhibitors in Section 6.9 (Table 7) should be followed
- Female participants are eligible to participate if they are not pregnant or breastfeeding and must be of nonchildbearing potential or (if women of childbearing potential [WOCBP]) must agree to use highly effective methods of contraception during the study and for at least 21 weeks after the last dose of study treatment. WOCBP must have a negative urine pregnancy test at screening and a negative urine pregnancy test at Week 0/Day 1 before initiation of study treatment. See Appendix 4 for the definition of nonchildbearing potential, childbearing potential, and highly effective methods of contraception. NOTE: Additional precautions in WOCBP may be required beyond 21 weeks after the last dose of study treatment due to use of any other concomitant medications. Please refer to the relevant local prescribing information for the relevant medications.
- Male participants must be willing to use a condom when sexually active with a partner of childbearing potential during the study and for at least 8 weeks after the last dose of study treatment, unless surgically sterile.
- Participants are considered reliable and capable of adhering to the protocol, visitschedule, or medication intake, according to the judgment of the investigator.
- Participants are able to understand and provide signed informed consent (See Appendix 1).
Exclusion Criteria
- Participants with a known hypersensitivity to sonelokimab or any of its excipients.
- Participants with fibromyalgia, reactivated osteoarthritis, or any other condition that in the investigator’s opinion may potentially interfere with efficacy assessments.
- Participants with a history of a lymphoproliferative disorders, including lymphoma, or current signs and symptoms suggestive of lymphoproliferative disease.
- Participants with primary immunodeficiencies, prior splenectomy, or suppressive conditions, including participants taking immunosuppressive therapy following organ transplants.
- Participants who have had major surgery (including joint surgery) within 6 months before the Baseline Visit or are planning to have major surgery during the study.
- Participants with severe cardiovascular comorbidities including history of myocardial infarction, unstable angina pectoris, stroke, heart failure (New York Heart Association classification III or IV), or uncontrolled hypertension (characterized by 2 BP measurements separated by ≥15 minutes with systolic BP >160 mmHg or diastolic BP>100 mmHg).
- Participants with any other clinically significant medical conditions or any other reason, including any physical, psychological, or psychiatric condition that could, in the opinion of the investigator, compromise the participant’s safety, interfere with their participation in the study, make the participant an unsuitable candidate to receive study treatment, or put the participant at risk.
- Participants who currently use or plan to use one or more of the prohibited treatments specified in this protocol (unless permitted according to criteria in Section 6.9.)
- Participants who have received a live (including attenuated) vaccination within 8 weeks before the Baseline Visit or have a firm medical indication to receive a live vaccination during the study and up to 8 weeks after the last dose of study treatment. Examples of restricted vaccinations include, but are not limited to: a. Zoster vaccine live (Zostavax). b. Measles-mumps-rubella or measles-mumps-rubella-varicella. c. Monovalent live attenuated influenza A (intranasal). d. Oral polio. e. Rotavirus. f. Seasonal trivalent live attenuated influenza (intranasal). g. Smallpox. h. Oral typhoid. i. Varicella (chicken pox). j. Yellow fever. k. Participants who have received a Bacillus Calmette-Guérin vaccination within 1 year before the Baseline Visit.
- Participants with clinically significant ECG abnormalities on centrally read ECG at the Screening Visit. Clinically significant ECG abnormalities are considered changes that often indicate underlying cardiac conditions that may require immediate medical attention.
- Participants with laboratory abnormalities at the Screening Visit, including any of the following: a. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase (ALP) >3×upper limit of normal (ULN). b. Serum direct bilirubin >1.5×ULN (in the absence of known Gilbert’s syndrome). c. White blood cell count <3.0×109/L. d. Absolute neutrophil count <1.5×109/L. e. Absolute lymphocyte count <0.8×109/L. f. Platelet count <100×109/L. g. Hemoglobin <85 g/L. h. Creatinine clearance <30 mL/min.
- Participants who have experienced a period of ≥3 consecutive weeks of unexplained diarrhea in the 24 weeks before the Baseline Visit.
- Any other laboratory abnormality that could, in the opinion of the investigator, compromise the participant’s safety, prevent the participant from completing the study, or interfere with the interpretation of the study results.
- Participants who have a history of chronic alcohol or drug abuse in the past year before the Screening Visit.
- Participants who are an employee or a direct relative of an employee of the sponsor, a study center, or a third-party organization involved in the study.
- Participants who have an active infection or history of infections, including any of the following: a. Any infection (exception: common cold) requiring systemic treatment within 14 days before the Baseline Visit. b. Serious infection, defined as infection requiring hospitalization or intravenous anti-infective treatment, within 2 months before the Baseline Visit. c. History of opportunistic infections caused by uncommon pathogens (eg, Pneumocystis jirovecii, Blastomyces, aspergillus, cryptococcosis), or severe infections caused by common pathogens (eg, cytomegalovirus, severe herpes zoster [ie, multidermatomal herpes zoster, herpes zoster with organ involvement, ophthalmic herpes, or recurrent herpes zoster, defined as 2 episodes within 2 years before the Baseline Visit]). d. History of other opportunistic, recurrent, or chronic infections that, in the opinion of the investigator, might cause study participation to be detrimental to the participant. e. Candida infection requiring systemic therapy for ≥7 days in the last 12 months before the Baseline Visit. f. Any history of esophageal or systemic candidiasis. g. Current active candidiasis or Candida infection within the 1 month before the Baseline Visit. h. Concurrent acute or chronic viral hepatitis B or C, or human immunodeficiency virus (HIV).
- Participants with a known hypersensitivity, or any contraindication, to risankizumab or any of its excipients or component of the container.
- Participants who have a diagnosis of chronic inflammatory conditions other than PsO or PsA, including but not limited to rheumatoid arthritis, reactive arthritis, enteropathic arthritis, ankylosing spondylitis, sarcoidosis, atopic dermatitis, and systemic or cutaneous lupus erythematosus.
- Participants with a confirmed or suspected diagnosis of inflammatory bowel disease (eg,ulcerative colitis or Crohn’s disease), either in medical history or currently present.
- Participants who currently, or in their history, have an established diagnosis of arthritis mutilans. Note: participants with any other PsA clinical subtype (eg, symmetrical polyarthritis, asymmetrical oligoarthritis, distal interphalangeal arthritis, and arthritis with axial involvement) are eligible for the study.
- Previous exposure to sonelokimab.
- Previous exposure to any other biologic immunomodulating agents for PsA or PsO whether investigational or approve
- Participants with evidence of TB infection (active, history of active, latent or history of latent) at the Screening Visit.
- Participants with any current nontuberculous mycobacterial infection or any history of nontuberculous mycobacterial infection at the Screening Visit.
- Participants with a concurrent malignancy or a history of malignancy during the past 5 years of the Baseline Visit, with the following exceptions: a. ≤3 excised or ablated basal cell carcinomas of the skin. b. One squamous cell carcinoma of the skin not worse than Stage T1 that has been successfully excised or ablated (no other previous treatments allowed), with no signs of recurrence or metastases for ≥2 years before the Baseline Visit. c. Actinic keratosis. d. Squamous cell carcinoma in situ of the skin successfully excised or ablated at >6 months before the Baseline Visit. e. Localized carcinoma in situ of the cervix, treated and considered cured.
- Participants with erythrodermic, guttate, or pustular form of PsO or drug-induced PsO.
- Participants who have ever received any investigational agent for PsA or PsO, if given ≤ 5 half-lives prior to randomization.
- Participants who have ever received any biologic treatment for any other indication, if given ≤ 5 half-lives prior to randomization.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Bulgaria | Recruiting | 02 May 2025 | 70 |
 Czechia | Recruiting | 02 May 2025 | 35 |
 France | Recruiting | 02 May 2025 | 15 |
 Germany | Recruiting | 02 May 2025 | 45 |
 Hungary | Recruiting | 02 May 2025 | 35 |
 Poland | Recruiting | 02 May 2025 | 137 |
 Spain | Recruiting | 02 May 2025 | 35 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Skyrizi 150 mg solution for injection in pre-filled syringe | Comparator | SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE | SUBCUTANEOUS INJECTION | 150 | 40 | PRD8999092 |
Sonelokimab | Test | INJECTION | SUBCUTANEOUS INJECTION | 60 | 48 | PRD10271601 |
Sonelokimab | Test | INJECTION | SUBCUTANEOUS INJECTION | 120 | 48 | PRD10271602 |
Placebo is a sterile solution in a single use prefilled syringe (PFS) intended for subcutaneous administration. | Placebo | N/A | — | — | — | N/A |