A Phase 2 open-label imaging study to explore the effects of sonelokimab in patients with active 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 Dec 2024 → 5 Jan 2026

Decision date (initial)

2024-11-18

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 reduction of inflammatory activity as measured by 18NaF maximum signal tracer uptake on positron emission tomography (PET) scan (SUVmax).

Secondary objectives 11

1. To assess the reduction of inflammatory activity as measured by 18NaF mean signal tracer uptake on PET scan (SUVmean) at Week 12.
2. To assess the changes in inflammatory and structural lesions as detected by magnetic resonance imaging (MRI) and PET scan at Week 12.
3. To assess the change in structural MRI lesions at Week 12.
4. To assess the change in disease activity clinical scores.
5. To assess the change in physical function.
6. To assess the change in spinal mobility.
7. To assess the change in enthesitis.
8. To assess the change in PROs.
9. To assess the safety and tolerability of sonelokimab.
10. To assess the pharmacokinetics (PK) and immunogenicity of sonelokimab.
11. To assess the effect of sonelokimab on biomarkers.

Conditions and MedDRA coding

axial spondyloarthritis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Participants must be ≥18 years of age at the time of signing the informed consent.
2. Participant has nr-axSpA diagnosis with all of the following criteria: 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 4 weeks prior to Screening) or positive 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 SI joints and according to the ASAS classification criteria with documented radiologic evidence (observed within 1 year prior to Screening).
3. 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.
4. Presence of signs of active disease on MRI of the SI joints or spine not older than 4 weeks prior to screening.
5. Presence of signs of active disease as defined by positive NaF-PET.
6. Participants are ideally naïve to bDMARDs or tsDMARDs, or may have received: a. up to 2 prior TNFi b. Up to 1 IL-12/23p40 or up to 1 IL-23p19 inhibitors c. Up to 1 JAKi
7. Sacroiliac joint radiographs, taken from routine visit, must be available within 12 months prior to Screening, to determine the presence of radiographic changes in the SI joints and that the patients fulfill the ASAS classification criteria.
8. Female participants are eligible to participate if they are not pregnant or breastfeeding and must be of nonchildbearing potential or, if 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 pregnancy test at Screening and a negative urine test at Week 0/Day 1 before initiation of study treatment. See Appendix 4: Contraceptive and Barrier Guidance for the definition of nonchildbearing potential, childbearing potential, and highly effective methods of contraception.
9. Male participants must be willing to use a condom when sexually active with a WOCBP partner during the study and for at least 8 weeks after the last dose of study treatment, unless surgically sterile.
10. 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: Regulatory, Ethical, and Study Oversight Considerations, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion criteria 28

1. Participants with a known hypersensitivity to sonelokimab or any of its excipients; participants with a known hypersensitivity to 18F-fluoride sodium or any of its excipients.
2. Participants with total ankylosis of the spine.
3. Diagnosis of rheumatic inflammatory diseases or conditions other than axSpA, e.g., rheumatoid arthritis, PsA, sarcoidosis, systemic lupus erythematosus, enteropathic or reactive arthritis.
4. 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 axSpA.
5. 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.
6. Participants with a confirmed or suspected diagnosis of IBD (e.g., ulcerative colitis or Crohn’s disease), either in medical history or currently present. 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).
7. Participants with evidence of acute ocular inflammation, including active anterior uveitis (i.e., acute episode), within the last 4 weeks before the Baseline Visit.
8. Participants who have experienced a period of ≥3 weeks of unexplained diarrhea in the 24 weeks before the initiation of study treatment.
9. 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. Previous esophageal or systemic candidiasis. e. Current active candidiasis or Candida infection within the last 3 months before the initiation of study treatment. f. 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]). 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.
10. 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).
11. Participants with any current nontuberculous mycobacterial infection or any history of nontuberculous mycobacterial infection at Screening.
12. Participants with a concurrent acute or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at the Screening.
13. Participants with evidence of human immunodeficiency virus (HIV) infection at Screening.
14. 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.
15. Participants with a history of a lymphoproliferative disorder including lymphoma or current signs and symptoms suggestive of lymphoproliferative disease.
16. Participants with primary immunodeficiencies, prior splenectomy, or suppressive conditions, including participants taking immunosuppressive therapy following organ transplants.
17. 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.
18. 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.
19. Participants who are unsuitable for IL-17A/IL-17F therapy according to the investigator’s discretion.
20. Participants who are or were enrolled in another interventional investigational study for a device or drug within the last 6 months or within 5 half-lives of the investigational before Screening, whichever is longer.
21. Participants with the following laboratory abnormalities at Screening: 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 <60 mL/min (by Cockcroft Gault formula).
22. 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.
23. 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.
24. Participants who have a history of chronic alcohol or drug abuse in the past year before the Screening.
25. 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.
26. For participants with biopsy samples taken: history of clinically relevant coagulation disorders or medication or known hypersensitivity against local anesthetics.
27. Participants defined as primary non-responder 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.
28. Participants with previous exposure to anti-IL-17RA (e.g., brodalumab), and/or anti-IL- 17A/F therapies (e.g., bimekizumab), including sonelokimab.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in 18F-NaF SUVmax signals at Week 12 in the sacroiliac joints (SIJ) and spine as detected by PET scan.

Secondary endpoints 26

1. Change from baseline in 18F-NaF SUVmean signals at Week 12 in the SIJ and spine as detected by PET scan.
2. Change from baseline in the number of SIJ quadrants and vertebral corners with 18F-NaF uptake at Week 12 as detected by PET scan.
3. Change from baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) MRI score in SIJ and spine (separately) at Week 12.
4. Proportion of participants with a decrease, no change or increase from baseline in SPARCC MRI score in SIJ and spine (separately) at Week 12.
5. Change from baseline in sacroiliac joint structural (SSS) score at Week 12.
6. Proportion of participants with a decrease, no change or increase from baseline in SSS score at Week 12.
7. Change from baseline in Ankylosing Spondylitis Disease Activity Creactive protein (ASDAS-CRP) at Week 12.
8. Proportion of participants with ASDAS status (inactive disease, moderate, high, and very high disease activity) over 12 weeks.
9. Proportion of participants who achieve ASDAS clinically important improvements at Week 12.
10. Proportion of participants who achieve Assessment of Spondyloarthritis International Society (ASAS) 20 and ASAS40 response at Week 12.
11. Change from baseline in Physician’s Global Assessment of Disease Activity (PhGADA) score over 12 weeks.
12. Change from baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score over 12 weeks.
13. Change from baseline in swollen joint count of 66 joints/tender joint count of 68 joints (SJC66/TJC68) over 12 weeks.
14. Change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) score over 12 weeks.
15. Change from baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) (linear) score over 12 weeks.
16. Change from baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) over 12 weeks.
17. Change from baseline at Week 12 in: o Patient’s Global Assessment of Disease Activity (PtGADA)-NRS o Work Productivity and Activity Impairment (WPAI) domain scores o ASAS-Health Index (ASAS-HI).
18. Change from baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score at Week 4 and Week 12.
19. Change from baseline in total and nocturnal spinal pain as assessed on a numerical rating scale (NRS) over 12 weeks.
20. Incidence, seriousness, relatedness, and severity of adverse events (AEs) and treatment-emergent adverse events (TEAEs) over 16 weeks.
21. TEAEs /AEs leading to study withdrawal over 16 weeks.
22. Adverse events of special interest (AESIs) over 16 weeks.
23. Abnormal laboratory parameters (hematology, clinical chemistry, urinalysis) over 16 weeks.
24. PK of sonelokimab (trough levels)
25. Antidrug antibodies
26. Change from baseline in exploratory biomarkers levels over 12 weeks.

Investigational products

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

Test 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 10

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 18 files

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

Application history

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