A Phase 2, open-label, imaging study to explore the effects of sonelokimab in patients with active psoriatic arthritis or axial spondyloarthritis

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]

Trial duration

23 Sep 2025 → ongoing

Decision date (initial)

2025-03-18

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: Efficacy, Safety

To assess the change in disease activity as measured by [68Ga]-fibroblast activation protein inhibitor (FAPI)- tracer uptake on FAPI-positron emission tomography (PET)/low-dose computed tomography (CT) scan (standardized uptake value [SUV]max) per lesion at Week 12.

Secondary objectives 18

1. To assess the change in disease activity as measured by 68Ga-FAPI tracer uptake SUVmean) at Week 12.
2. PsA only: To assess the change in inflammatory lesions based on magnetic resonance imaging (MRI) or ultrasound at Week 12.
3. PsA only: To assess the change in PsA symptoms at Week 12.
4. PsA only: To assess the change in disease activity using clinical scores at Week 12.
5. PsA only: To assess the change in psoriasis severity at Week 12.
6. PsA only: To assess the change in nail psoriasis severity at Week 12.
7. PsA only: To assess the change in physical function at Week 12.
8. PsA only: To assess the change in enthesitis at Week 12.
9. PsA only: To assess the change in dactylitis at Week 12.
10. PsA only: To assess the change in PROs at Week 12.
11. To assess the safety and tolerability over Week 16.
12. To assess the PK and immunogenicity.
13. To assess the effect of sonelokimab on biomarkers.
14. axSpA only: To assess the changes in inflammatory and structural lesions as detected by MRI and FAPI-PET/low-dose CT at Week 12.
15. axSpA only: To assess the change in disease activity using clinical scores at Week 12.
16. axSpA only: To assess the change in physical function at Week 12.
17. axSpA only: To assess the change in enthesitis at Week 12.
18. axSpA only: To assess the change in participant-reported outcomes (PROs) at Week 12.

Conditions and MedDRA coding

psoriatic arthritis

Regulatory references

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. Participants must be ≥18 years of age at the time of signing the informed consent form (ICF).
2. PsA only: Participant tests negative for anti-cyclic citrullinated peptide antibodies at Screening.
3. PsA only: Participant should have active PsA and must have at least 1 of the following:  Inadequate response to previous or current treatment with ≥1 non-biologic conventional DMARD (csDMARDs) at the maximally tolerated dose given for at least 12 weeks.  Intolerance to csDMARDs administration.  Contraindication(s) to csDMARD therapy.
4. axSpA only: Participant has nr-axSpA diagnosis with all of the following criteria (2009), adult-onset axSpA meeting ASAS classification criteria, inflammatory back pain for at least 3 months, age at symptom onset of less than 45 years, show disease activity on MRI in the SIJ or spine (observed within 8 weeks prior to Baseline) or positive C-Reactive protein (CRP) but NO radiographic evidence of sacroiliitis (in anterior-posterior pelvis or sacroiliac x-ray, not older than 12 months) OR Diagnosis of r-axSpA by the treating rheumatologist and classification based on the presence of radiographic damage in the SIJ and according to the ASAS classification criteria with documented radiologic evidence (observed within 1 year prior to Screening).
5. axSpA only: Evidence of active disease, based on a BASDAI score of ≥4 despite treatment with a full dose of at least 2 NSAIDs for ≥4 weeks prior to Screening.
6. axSpA only: Presence of signs of active disease on MRI of the SIJ or spine conducted within 8 weeks prior to Baseline.
7. axSpA only: SIJ radiographs, taken from routine visit, must be available within 12 months prior to Screening, to determine the presence of radiographic changes in the SIJ.
8. Positive FAPI-PET/CT (i.e., indication of high mesenchymal inflammatory disease activity).
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 serum human chorionic gonadotropin (hCG) pregnancy test at Screening and a negative urine pregnancy test at Week 0/Day 1 prior to the first administration of study treatment. See Appendix 4: Contraceptive and Barrier Guidance for the definition of nonchildbearing potential, childbearing potential, and highly effective methods of contraception.
10. Male participants must be willing to use a condom when sexually active with a WOCBP partner during the study and for at least 12 weeks after the last dose of study treatment, unless surgically sterile.
11. Participants are considered reliable and capable of adhering to the protocol, visit schedule, or medication intake, according to the judgment of the investigator and must be capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
12. PsA only: Participant has a confirmed diagnosis of PsA per the 2006 Classification Criteria for Psoriatic Arthritis (CASPAR) with symptoms for ≥3 months prior to Screening.
13. PsA only: Participant has evidence of active disease (defined by a TJC68 of ≥1 and a SJC66 of ≥1, OR ≥1 entheseal swelling or pain).
14. PsA only: Signs of inflammation (enthesitis, tendinitis, synovitis, dactylitis) in clinical investigation and/or ultrasound and/or MRI, maximum 8 weeks prior to baseline
15. PsA only: Participant has either current active psoriasis, nail changes consistent with psoriasis, or a history of psoriasis.

Exclusion criteria 34

1. Participants with a known hypersensitivity to sonelokimab or any of its excipients; participants with a known hypersensitivity to 68Ga-FAPI or any of its excipients.
2. Participants with evidence of TB infection (active, history of active, latent or history of latent) at Screening. Participants may still enter the study if they have documented evidence that they have completed sufficient treatment, according to local routine clinical practice, at least 4 weeks before randomization. If they completed their treatment at least 4 weeks before and within 24 months of the Baseline Visit, to be enrolled they need to have documented evidence of treatment and have no evidence of active or latent disease. If they completed their treatment over 24 months before baseline, to be enrolled they need to have been adequately treated and confirmed to be fully recovered upon consultation with a TB specialist (see Section 8.1.3).
3. Participants with any current nontuberculous mycobacterial infection or any history of nontuberculous mycobacterial infection at Screening.
4. Participants with a concurrent acute or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at the Screening.
5. Participants with evidence of human immunodeficiency virus (HIV) infection at Screening.
6. Participants with a concurrent malignancy or a history of malignancy within 5 years of the initiation of study treatment with the following exceptions: a. Three or fewer successfully 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 treated, with no signs of recurrence or metastases for at least the past 2 years before study treatment initiation. c. Actinic keratosis. d. Squamous cell carcinoma in situ of the skin successfully treated >6 months before study treatment initiation. e. Localized carcinoma in situ of the cervix treated and considered cured.
7. Participants with a history of a lymphoproliferative disorder including lymphoma or current signs and symptoms suggestive of lymphoproliferative disease.
8. Participant with fibromyalgia, osteoarthritis symptoms, or any other condition that in the investigator’s opinion may potentially interfere with efficacy assessments.
9. Participants with primary immunodeficiencies, prior splenectomy, or suppressive conditions, including participants taking immunosuppressive therapy following organ transplants.
10. Participants who currently use or plan to use one or more prohibited treatments specified in this protocol (Section 6.10.2). Prohibited treatments and washout periods are described in Table 7, along with the permitted medications.
11. 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.
12. Participants with total ankylosis of the spine.
13. Participants who are enrolled in another interventional investigational study for a device or drug, or that have been enrolled in the last 28 days before the initiation of study treatment or within 5 half-lives of the investigational study drug before the initiation of study treatment, whichever is longer.
14. Participants with clinically significant laboratory abnormalities at the Screening, including any of the following: a. AST, ALT, or ALP >3×ULN. b. Serum direct bilirubin >1.5×ULN (in the absence of known Gilbert syndrome). c. White blood cell count <3.0×109/L. d. Absolute neutrophil count <1.5×109/L. e. Absolute lymphocyte count <0.7×109/L. f. Platelet count <100×109/L. g. Hemoglobin <85 g/L. h. Creatinine clearance <30 mL/min (by Cockcroft Gault formula).
15. Participants with any other laboratory abnormality which, in the opinion of the investigator, might compromise participant’s safety, prevent the participant from completing the study or would interfere with the interpretation of the study results.
16. Participants with severe cardiovascular comorbidities including history of myocardial infarction, unstable angina pectoris, stroke, heart failure (New York Association [NYHA classification III or IV]), or uncontrolled hypertension (characterized by 2 BP measurements separated at least 15 minutes with systolic BP >160 mmHg or diastolic BP >100 mmHg).
17. Participants who have had major surgery (e.g., joint surgery, hip replacement) within 6 months before the initiation of study treatment or are planning to have major surgery during the study.
18. Participants who have a history of chronic alcohol or drug abuse in the past year before the Screening.
19. Participants with any other clinically significant medical conditions or any other reasons, including any physical, psychological, or psychiatric condition, that in the opinion of the investigator would compromise the safety or interfere with participation in the study, would make the participant an unsuitable candidate to receive study treatment, or would put the participant at risk.
20. 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. For participants with biopsy samples taken: history of clinically relevant coagulation disorders or medication that, after discussion between the investigator and medical monitor, are considered to pose a significant risk of bleeding during biopsy, or known hypersensitivity against local anesthetics.
22. Participants who currently, or in their history, have an established diagnosis of arthritis mutilans a. Note: participants with any other PsA clinical subtype (e.g., symmetrical polyarthritis, asymmetrical oligoarthritis, distal interphalangeal arthritis, and arthritis with axial involvement) are eligible for the study.
23. Diagnosis of rheumatoid arthritis, systemic or cutaneous lupus erythematosus, reactive arthritis, enteropathic arthritis, or sarcoidosis
24. Participants with erythrodermic, guttate, or pustular form of psoriasis or drug-induced psoriasis.
25. Participants who have ever received more than two compounds of either bDMARDs (TNF inhibitors, IL-12/23 p40, IL-23 p19 inhibitors, or abatacept) or tsDMARDs (e.g., JAKi, tyrosine kinase 2 [TYK2] inhibitors) for PsA, psoriasis, or axSpA, whether investigational or approved, in any successive combination and order of use.
26. Participants who are unsuitable for IL-17A/IL-17F therapy according to the investigator’s discretion.
27. Participants defined as primary non-responders on anti-IL-17A therapy, according to the investigator’s judgment or are unsuitable for anti-IL-17A therapy for any other reason according to the investigator’s discretion. Washout period is described in Table 7 (Section 6.10.2).
28. Participants with previous exposure to anti-IL-17RA (e.g., brodalumab), and/or anti-IL-17A/F therapies (e.g., bimekizumab), including sonelokimab.
29. Participants with any other active rheumatic and/or inflammatory disease or condition that may, in the opinion of the investigator, interfere with the assessment of PsA or axSpA.
30. Participants with current severe or uncontrolled disease(s) or with underlying conditions that put(s) the participant at increased risk, including any medical or psychiatric condition that, in the investigator’s opinion, potentially places the participant at unacceptable risk or would preclude the participant from adhering to the protocol or completing the study per protocol.
31. Participant with evidence of acute ocular inflammation, including active anterior uveitis (i.e., acute episode), within the last 4 weeks before the Baseline Visit.
32. Participants with a confirmed or suspected diagnosis of IBD (e.g., ulcerative colitis or Crohn’s disease), either in medical history or currently present. a. Note: participants with functional gastrointestinal disorders (e.g., Irritable Bowel Syndrome) can be considered eligible for enrolment if IBD has been excluded and documented (e.g., formal clinical criteria, endoscopy, fecal calprotectin stool test).
33. Participants who have experienced a period of ≥3 weeks of unexplained diarrhea in the 24 weeks before the initiation of study treatment.
34. Participants with an active infection or history of infections including any of the following: a. Any infection (exception: common cold) requiring systemic anti-infective treatment within 14 days before initiation of study treatment. b. Serious infection, defined as requiring hospitalization or intravenous antiinfectives, within 2 months before initiation of study treatment. c. Candida infection requiring systemic therapy for ≥7 days in the last 12 months before initiation of study treatment. d. Any history of esophageal or systemic candidiasis. e. Current active candidiasis or Candida infection within the last 1 month before Baseline Visit. f. History of opportunistic infections caused by uncommon pathogens (e.g., Pneumocystis jirovecii, Blastomyces, Aspergillus, Cryptococcosis), or severe infections caused by common pathogens (e.g., cytomegalovirus, severe herpes zoster [i.e., 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]). g. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in 68Ga-FAPI SUVmax signal per lesion at Week 12, as detected by FAPI-PET/low-dose CT 46 scan, overall and per indication.

Secondary endpoints 48

1. Change from baseline in 68Ga-FAPI SUVmean signal at Week 12, as detected by FAPI-PET/low-dose CT scan, overall and per indication.
2. PsA only: Change from baseline in psoriatic arthritis magnetic resonance imaging scoring system (PsAMRIS) or global OMERACT EULAR ultrasound synovitis score (GLOESS) at Week 12.
3. PsA only: Proportion of participants with PsAMRIS or GLOESS change at Week 12.
4. PsA only: Proportion of participants who achieve American college of rheumatology (ACR)20, ACR50 and ACR70 at Week 12.
5. PsA only: Proportion of participants who achieve ACR20, ACR50, ACR70, and ACR90 responses over 12 weeks (except Week 12 for ACR20, ACR50 and ACR70).
6. PsA only: Change from baseline in disease activity in psoriatic arthritis (DAPSA) score over 12 weeks.
7. PsA only: Change from baseline in psoriatic arthritis disease activity score (PASDAS) score over 12 weeks.
8. PsA only: Proportion of participants with PASDAS categories (remission; low, moderate, and high disease activity) over 12 weeks.
9. PsA only: Change from baseline in disease activity score 28 using C-reactive protein (DAS28-CRP) score over 12 weeks.
10. PsA only: Change from baseline in Psoriatic Arthritis Response Criteria (PsARC) score over 12 weeks.
11. PsA only: Proportion of participants achieving minimal disease activity (MDA) at Week 12.
12. PsA only: Proportion of participants achieving very low disease activity (VLDA) at Week 12.
13. PsA only: Change from baseline in physician global assessment of disease activity (PhGADA) score over 12 weeks.
14. PsA only: Change from baseline in Bath ankylosing spondylitis disease activity index (BASDAI) score over 12 weeks.
15. PsA only: Change from baseline in 66 swollen joint count and 68 tender joint count (SJC66/TJC68) over 12 weeks.
16. PsA only: Percentage change from baseline in psoriasis area severity index (PASI) score over 12 weeks.
17. PsA only: Proportion of participants achieving PASI 50, PASI 75, PASI 90, and PASI 100 responses over 12 weeks.
18. PsA only: Change from baseline in modified nail psoriasis severity index (mNAPSI) score over 12 weeks.
19. PsA only: Change from baseline in health assessment questionnaire - disability index (HAQ-DI) score over 12 weeks.
20. PsA only: Change from baseline in Leeds enthesitis index (LEI) enthesitis score over 12 weeks.
21. PsA only: Proportion of participants enthesitis-free according to LEI over 12 weeks.
22. PsA only: Change from baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) enthesitis index over 12 weeks.
23. PsA only: Proportion of participants enthesitis-free based on the SPARCC enthesitis score over 12 weeks.
24. PsA only: Change from baseline in Maastricht ankylosing spondylitis enthesitis score (MASES) over 12 weeks.
25. PsA only: Change from baseline in Leeds dactylitis index (LDI) over 12 weeks.
26. PsA only: Proportion of participants dactylitis-free according to LDI over 12 weeks.
27. PsA only: Change from baseline over 12 weeks in:  Patient global assessment of disease activity (PtGADA)  Patient’s assessment of arthritis pain (PtAAP)  Psoriatic assessment impact of disease (PsAID-12)  Functional assessment of chronic illness therapy (FACIT)-Fatigue  Short form-36 (SF-36) v2  Work productivity and activity impairment (WPAI) questionnaire for specific health problem (WPAI:PsA)  Psoriatic Arthritis Quality of Life (PsAQoL).
28. Incidence, seriousness, relatedness, and severity of adverse events (AEs) and treatment-emergent adverse events (TEAEs) over 16 weeks.
29. AEs / TEAEs leading to study withdrawal over 16 weeks.
30. Adverse events of special interest (AESIs) over 16 weeks.
31. Abnormal laboratory parameters (hematology, clinical chemistry, urinalysis) over 16 weeks.
32. PK of sonelokimab (trough levels).
33. Antidrug antibodies
34. Change in exploratory biomarker levels before and after treatment.
35. axSpA only: Change from baseline in the number of SIJ quadrants and vertebral corners with [68Ga]-FAPI uptake at Week 12, as detected by FAPI-PET/low-dose CT scan.
36. axSpA only: Change from baseline in SPARCC MRI score in SIJ and spine (separately).
37. axSpA only: Proportion of participants with a decrease, no change or increase from baseline in SPARCC MRI score at Week 12 in SIJ and spine (separately).
38. axSpA only: Change from baseline in sacroiliac joint structural score (SSS) at Week 12.
39. axSpA only: Proportion of participants with a decrease, no change or increase from baseline in SSS score at Week 12.
40. axSpA only: Change from baseline in ankylosing spondylitis disease activity score (ASDAS)- C-Reactive Protein (CRP) over Week 12.
41. axSpA only: Proportion of participants with ASDAS-CRP status (inactive disease, moderate, high, and very high disease activity) over 12 weeks.
42. axSpA only: Proportion of participants who achieve ASDAS-CRP clinically important improvement (≥ 1.1 units) at Week 12.
43. axSpA only: Proportion of participants who achieve assessment of spondyloarthritis international society (ASAS)20 and ASAS40 responses at Week 12.
44. axSpA only: Change from baseline in BASDAI score over 12 weeks.
45. axSpA only: Change from baseline in SJC66/TJC68 over 12 weeks.
46. axSpA only: Change from baseline in Bath ankylosing spondylitis functional index (BASFI) score over 12 weeks.
47. axSpA only: Change from baseline in MASES over 12 weeks.
48. axSpA only: Change from baseline over 12 weeks in PtGADA.

Investigational products

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

Test 1

Auxiliary 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

Kristian Reich

Public contact point

Organisation

MoonLake Immunotherapeutics AG

Contact name

Kristian Reich

Third parties 8

Locations

1 EU/EEA country · 1 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 21 files

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

Application history

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