A study to investigate the efficacy and safety of subcutaneous sonelokimab versus placebo and risankizumab (active reference arm) in participants aged 18 years and over with active psoriatic arthritis and antiTNFα inadequate response.

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] - Musculoskeletal Diseases [C05], 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

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the efficacy of sonelokimab 60 mg and 120 mg (Arms 1 and 2) at Week 16 compared with placebo (Arm 3) using ACR50 response criteria in participants with active PsA.

Secondary objectives 3

1. 1. To evaluate the efficacy of sonelokimab 60 mg and 120 mg (Arms 1 and 2) at Week 16 compared with placebo (Arm 3) in participants with active PsA
2. 2. To evaluate the efficacy of sonelokimab 60 mg and 120 mg (Arms 1 and 2) at Week 16 compared with risankizumab (Arm 4) in participants with active PsA
3. 3. To evaluate the safety and tolerability of sonelokimab 60 mg and 120 mg 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 moderate to severe active disease (defined by a TJC68 of ≥3 and a SJC66 of ≥3).
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 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.
6. 6. Participants who test negative for both rheumatoid factor and anti-cyclic citrullinated peptide at the Screening Visit.
7. 7. 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.
8. 8. 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
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 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.
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.
11. 11. Participants are considered reliable and capable of adhering to the protocol, visitschedule, or medication intake, according to the judgment of the investigator.
12. 12. Participants are able to understand and provide signed informed consent (See Appendix 1).

Exclusion criteria 28

1. 1. Participants with a known hypersensitivity to sonelokimab or any of its excipients.
2. 17. Participants with fibromyalgia, reactivated osteoarthritis, or any other condition that in the investigator’s opinion may potentially interfere with efficacy assessments.
3. 19. Participants with a history of a lymphoproliferative disorders, including lymphoma, or current signs and symptoms suggestive of lymphoproliferative disease.
4. 20. Participants with primary immunodeficiencies, prior splenectomy, or suppressive conditions, including participants taking immunosuppressive therapy following organ transplants.
5. 21. 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.
6. 22. 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).
7. 23. 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.
8. 24. 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.)
9. 25. 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.
10. 26. 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.
11. 27. 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.
12. 5. Participants who have experienced a period of ≥3 consecutive weeks of unexplained diarrhea in the 24 weeks before the Baseline Visit.
13. 28. 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.
14. 29. Participants who have a history of chronic alcohol or drug abuse in the past year before the Screening Visit.
15. 30. 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.
16. 13. 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).
17. 2. Participants with a known hypersensitivity, or any contraindication, to risankizumab or any of its excipients or component of the container.
18. 3. 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.
19. 4. 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.
20. 6. 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.
21. 7. Previous exposure to sonelokimab.
22. 8. Previous exposure to any other biologic immunomodulating agents for PsA or PsO whether investigational or approve
23. 14. Participants with evidence of TB infection (active, history of active, latent or history of latent) at the Screening Visit.
24. 15. Participants with any current nontuberculous mycobacterial infection or any history of nontuberculous mycobacterial infection at the Screening Visit.
25. 16. 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.
26. 18. Participants with erythrodermic, guttate, or pustular form of PsO or drug-induced PsO.
27. 9. Participants who have ever received any investigational agent for PsA or PsO, if given ≤ 5 half-lives prior to randomization.
28. 10. Participants who have ever received 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. 1. Proportion of participants achieving ACR50 (ie, ≥50% response on the ACR response criteria) at Week 16

Secondary endpoints 11

1. 1. Proportion of participants achieving ACR20 (ie, ≥20% response 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 PASI90 response at Week 16 in the subset 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. Proportion of participants achieving ACR50 at Week 16
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 2

Comparator 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

Fiona Guy

Public contact point

Organisation

MoonLake Immunotherapeutics AG

Contact name

Fiona Guy

Third parties 5

Locations

7 EU/EEA countries · 96 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 140 files

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

Application history

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