A study to investigate the efficacy and safety of subcutaneous sonelokimab versus placebo in participants aged 18 years and over with active psoriatic arthritis who are naive to biologic DMARDs

Overview

Sponsor-declared trial summary

Key facts

Sponsor

MoonLake Immunotherapeutics AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

25 Mar 2025 → ongoing

Decision date (initial)

2025-03-12

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

MoonLake Immunotherapeutics AG

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the efficacy of sonelokimab 60 mg Q4W with and without an induction regimen (Arms 1 and 2) at Week 16 compared with placebo (Arm 3) using ACR50 response criteria in participants with active psoriatic arthritis (PsA).

Secondary objectives 2

1. 1. To evaluate the efficacy of sonelokimab 60 mgQ4W with and without an induction regimen (Arms 1 and 2) at Week 16 compared with placebo (Arm 3) in participants with active PsA
2. 2. To evaluate the safety and tolerability of sonelokimab 60 mg Q4W with and without an induction regimen over time in the treatment of participants with active PsA

Conditions and MedDRA coding

Psoriatic arthritis

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. 1. Participants must be ≥18 years of age at the time of signing the informed consent.
2. 2. 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.
3. 3. Participants who have active disease (defined by a 68 tender joint count [TJC68] of ≥3 and a 66 swollen joint count [SJC66] of ≥3 at Screening Visit and confirmed at Randomization Visit).
4. 4. 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.
5. 5. Participants who test negative for both rheumatoid factor and anti-cyclic citrullinated peptide at the Screening Visit.
6. 6. Participants should have (a) been taking a stable dose of NSAIDs for a period of ≥4 consecutive weeks, any time prior to screening, with inadequate control of symptoms, or (b) should have a documented intolerance or contraindication to ≥1 NSAID.
7. 7. Participants should have had an inadequate response to ≥1 nonbiological conventional synthetic DMARDs (csDMARDs) [methotrexate, sulfasalazine, leflunomide], taken for at least 12 weeks (with a stable dose for ≥8 weeks), or should have a documented intolerance to or contraindication to at least one of these csDMARDs as defined by the investigator. Note: in case csDMARDs were discontinued before enrollment in this study, the washout requirements in Section 6.9 (Table 7) should be followed.
8. 8. Participants must have the presence of at least one of the following at the Screening Visit: (a) ≥1 erosion based on the Screening plain X-rays of hands and feet, as determined by centralized imaging review. (b) A hs-CRP value greater than the central laboratory-defined upper limit of normal.
9. 9. 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 8 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. Female participants of childbearing potential must refrain from donating oocytes during the study and for at least 8 weeks after the last dose of study treatment. See Appendix 4 for the definitions of nonchildbearing potential, childbearing potential, and highly effective methods of contraception.
10. 10. 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. Male participants must also agree to refrain from donating sperm during the study and for at least 8 weeks after the last dose of study treatment.
11. 11. Participants are considered reliable and capable of adhering to the protocol, visit schedule, or medication intake, according to the judgment of the investigator.
12. 12. Participants are able to understand and provide signed informed consent (see protocol Appendix 1).

Exclusion criteria 25

1. 1. Participants with a known hypersensitivity to sonelokimab or any of its excipients.
2. 12. 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).
3. 13. Participants with evidence of TB infection (active, history of active, latent or history of latent) at the Screening Visit.
4. 14. Participants with any current nontuberculous mycobacterial infection or any history of nontuberculous mycobacterial infection at the Screening Visit.
5. 15. 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.
6. 16. Participants with any condition that in the investigator’s judgement may potentially interfere with study efficacy assessments, including but not limited to fibromyalgia and reactivated osteoarthritis.
7. 17. Participants with erythrodermic, guttate, or pustular form of PsO or drug-induced PsO.
8. 18. Participants with a history of a lymphoproliferative disorder, including lymphoma, or current signs and symptoms suggestive of lymphoproliferative disease.
9. 19. Participants with primary immunodeficiencies, prior splenectomy, or suppressive conditions, including participants taking immunosuppressive therapy following organ transplants.
10. 2. 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.
11. 20. 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.
12. 21. Participants with severe cardiovascular comorbidities including but not limited to: documented history of myocardial infarction, unstable angina pectoris stroke, presence of heart failure (New York Heart Association classification III or IV), or evidence of severe, uncontrolled hypertension (characterized by 2 BP measurements separated by ≥15 minutes with systolic BP >180 mmHg or diastolic BP >120 mmHg).
13. 22. Participants with any other clinically significant medical conditions or any other reason, including any medical or surgical procedure or 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 or study data at risk.
14. 23. 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 protocol Section 6.9)
15. 24. Participants who have received a live (including attenuated) vaccination within 8 weeks before the Baseline Visit or plan 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.
16. 25. 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.
17. 26. 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. (c) White blood cell count <3.0×10^9/L. (d) Absolute neutrophil count <1.5×10^9/L. (e) Absolute lymphocyte count <0.8×10^9/L. (f) Platelet count <100×10^9/L. (g) Hemoglobin <85 g/L. (h) Creatinine clearance <30 mL/min
18. 27. 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.
19. 28. Participants who have a history of chronic alcohol or drug abuse in the past year before the Screening Visit.
20. 29. 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.
21. 3. 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.
22. 4. Participants who have experienced a period of ≥3 consecutive weeks of unexplained diarrhea in the 24 weeks before the Baseline Visit.
23. 5. 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.
24. 6. Previous exposure to sonelokimab.
25. 7. Participants who have ever received: (a) Any biologic immunomodulating agents for PsA or PsO, whether investigational or approved. (b) Any investigational agent for PsA or PsO, if given ≤ 5 half-lives prior to randomization. (c) Any biologic treatment for any other indication, if given ≤ 5 half-lives prior to randomization.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of participants achieving ACR50 (ie, ≥50% improvement on the ACR response criteria) at Week 16

Secondary endpoints 11

1. 1. Proportion of participants achieving ACR20 (ie, ≥20% improvement on the ACR response criteria) at Week 16
2. 2. Proportion of participants achieving Minimal Disease Activity (MDA) at Week 16
3. 3. Change from Baseline in Health Assessment Questionnaire—Disability Index (HAQ-DI) at Week 16
4. 4. Proportion of participants achieving a decrease of ≥90% in the Psoriasis Area and Severity Index (PASI90) response at Week 16 in the subgroup of participants with PsO involving ≥3% body surface area at Baseline
5. 5. Change from Baseline in SF-36 PCS at Week 16
6. 6. Change from Baseline to Week 16 in joint/bone structural damage (van der Heijde modified Total Sharp Score)
7. 7. Incidence, relatedness, severity, and seriousness of TEAEs
8. 8. Withdrawal due to TEAEs
9. 9. Clinically relevant abnormalities in vital signs (blood pressure and heart rate) and body weight
10. 10. Clinically relevant abnormalities in 12-lead ECG variables
11. 11. Clinically relevant abnormalities in laboratory parameters (hematology, biochemistry, and urinalysis)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

MoonLake Immunotherapeutics AG

Sponsor organisation

MoonLake Immunotherapeutics AG

Address

Dorfstrasse 29

City

Zug

Postcode

6300

Country

Switzerland

Scientific contact point

Organisation

MoonLake Immunotherapeutics AG

Contact name

Clinical Trial Information Point

Public contact point

Organisation

MoonLake Immunotherapeutics AG

Contact name

Clinical Trial Information Point

Third parties 6

Locations

16 EU/EEA countries · 154 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 323 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

13 submissions — initial application plus substantial / non-substantial modifications