Phase 2 Open-Label Imaging Study on Sonelokimab's Effects in Active Axial Spondyloarthritis Evaluated by 18NaF PET Scan Tracer Uptake

Trial ID: 2024-513498-36-00
Protocol: M1095-axSpA-202
Sponsor: MoonLake Immunotherapeutics AG

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Diseases & Conditions

Axial spondyloarthritis

Objectives

The primary objective of this Phase 2 open-label imaging study is to evaluate the **reduction of inflammatory activity** in patients with active **axial spondyloarthritis**. This is measured by the 18NaF maximum signal tracer uptake on positron emission tomography (PET) scan (SUVmax). The clinical relevance of this objective lies in its potential to demonstrate the efficacy of sonelokimab in reducing inflammation, which is a key factor in the management of axial spondyloarthritis.

Secondary objectives include:

Assessing the reduction of inflammatory activity as measured by 18NaF mean signal tracer uptake on PET scan (SUVmean) at Week 12.
Evaluating changes in inflammatory and structural lesions as detected by magnetic resonance imaging (MRI) and PET scan at Week 12.
Assessing changes in structural MRI lesions at Week 12.
Evaluating changes in disease activity clinical scores.
Assessing changes in physical function and spinal mobility.
Evaluating changes in enthesitis and patient-reported outcomes (PROs).
Assessing the safety and tolerability of sonelokimab.
Evaluating the pharmacokinetics (PK) and immunogenicity of sonelokimab.
Assessing the effect of sonelokimab on biomarkers.

These secondary objectives aim to provide a comprehensive understanding of the therapeutic effects and safety profile of sonelokimab in this patient population.

Participants

The clinical trial involves participants diagnosed with **axial spondyloarthritis**, including both non-radiographic and radiographic forms. The study population comprises adults aged 18 years and older, encompassing both male and female subjects. Participants are required to have a diagnosis of adult-onset axial spondyloarthritis, with inflammatory back pain persisting for at least three months and symptom onset before the age of 45. The trial includes individuals who exhibit active disease signs on MRI or positive NaF-PET, and those with a BASDAI score of 4 or higher despite prior NSAID treatment. Participants are ideally naïve to biologic or targeted synthetic DMARDs, although some may have received limited prior treatments with TNF inhibitors, IL-12/23p40, IL-23p19 inhibitors, or JAK inhibitors. Female participants must not be pregnant or breastfeeding and must adhere to effective contraception methods if of childbearing potential. Male participants are required to use condoms if sexually active with a woman of childbearing potential. The sponsor has not provided the total number of participants involved in the trial.

Plans and Procedures

The clinical trial is a **Phase 2 open-label study** designed to explore the effects of **sonelokimab** in patients with active **axial spondyloarthritis**. The primary objective is to assess the reduction of inflammatory activity as measured by 18NaF maximum signal tracer uptake on positron emission tomography (PET) scan (SUVmax). The trial is expected to commence recruitment on December 3, 2024, and conclude by May 5, 2026. Participants will receive **sonelokimab** via **subcutaneous injection**, with a maximum daily dose of 60 mg/ml and a total dose not exceeding 300 mg over the treatment period. The trial will span 16 weeks, with the treatment phase lasting up to 8 weeks.

The study involves several key visits, beginning with a screening visit to confirm eligibility based on criteria such as age, disease activity, and prior treatment history. Participants must be at least 18 years old and demonstrate active disease despite prior treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). The inclusion criteria also require evidence of active disease on MRI or PET scans. Following the screening, participants will undergo baseline assessments before initiating treatment. Subsequent visits will occur at regular intervals to monitor changes in disease activity, safety, and treatment response, with primary and secondary endpoints evaluated at Week 12. The end-of-study visit will include final assessments and evaluations of any adverse events or treatment-emergent adverse events (TEAEs).

Participant involvement is expected to last approximately 16 weeks, including follow-up. Conditions that may lead to early termination from the study include the occurrence of serious adverse events, non-compliance with the study protocol, or withdrawal of consent. The trial will employ various assessments, including changes in SUVmax and SUVmean signals, SPARCC MRI scores, and other disease activity indices. Safety evaluations will include monitoring adverse events, laboratory parameters, and the presence of antidrug antibodies. The study aims to provide valuable insights into the efficacy and safety of **sonelokimab** in treating **axial spondyloarthritis**.

Treatment

The clinical trial involves the administration of **Sonelokimab**, an experimental medication developed by Moonlake Immunotherapeutics AG. Sonelokimab is formulated as an **injection** and is classified as a protein of other origin. The active substance, sonelokimab, is administered via **subcutaneous injection**. The dosing regimen for this trial specifies a maximum daily dose of 60 mg/ml, with a total maximum dose of 300 mg/ml over the treatment period. The treatment duration is set for a maximum of 8 weeks. The pharmaceutical form of the medication is strictly for injection, and it is not a pediatric formulation. Compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus remains solely on evaluating the effects of Sonelokimab in patients with active **axial spondyloarthritis**. The primary objective is to assess the reduction of inflammatory activity as measured by 18NaF maximum signal tracer uptake on positron emission tomography (PET) scan (SUVmax). Participants' adherence to the treatment regimen is closely monitored to ensure the integrity of the trial data.

Efficacy

Efficacy in this clinical trial will be assessed by evaluating the reduction of inflammatory activity in patients with active axial spondyloarthritis. The primary endpoint is the change from baseline in **18F-NaF SUVmax** signals at Week 12 in the sacroiliac joints (SIJ) and spine, as detected by positron emission tomography (PET) scan. Secondary endpoints include changes from baseline in **18F-NaF SUVmean** signals, the number of SIJ quadrants and vertebral corners with **18F-NaF** uptake, and the Spondyloarthritis Research Consortium of Canada (SPARCC) MRI score in SIJ and spine at Week 12. Additional secondary endpoints involve the proportion of participants with changes in SPARCC MRI score, sacroiliac joint structural (SSS) score, and Ankylosing Spondylitis Disease Activity C-reactive protein (ASDAS-CRP) at Week 12. The trial will also assess the proportion of participants achieving ASDAS clinically important improvements, ASAS 20 and ASAS40 response, and changes in various disease activity and functional indices over 12 weeks. These include the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), and Maastricht Ankylosing Spondylitis Enthesitis Score (MASES). Patient-reported outcomes such as the Patient’s Global Assessment of Disease Activity (PtGADA), Work Productivity and Activity Impairment (WPAI) domain scores, and ASAS-Health Index (ASAS-HI) will also be measured. The Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score will be evaluated at Week 4 and Week 12. Changes in total and nocturnal spinal pain, as assessed on a numerical rating scale (NRS), will be monitored over 12 weeks. The trial will also track the incidence, seriousness, relatedness, and severity of adverse events (AEs) and treatment-emergent adverse events (TEAEs) over 16 weeks, including those leading to study withdrawal and adverse events of special interest (AESIs). Abnormal laboratory parameters, pharmacokinetics of sonelokimab, antidrug antibodies, and exploratory biomarker levels will be analyzed over 12 weeks.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Participants must be ≥18 years of age at the time of signing the informed consent.
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).
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.
Presence of signs of active disease on MRI of the SI joints or spine not older than 4 weeks prior to screening.
Presence of signs of active disease as defined by positive NaF-PET.
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
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.
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.
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.
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.

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Exclusion Criteria

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.
Participants with total ankylosis of the spine.
Diagnosis of rheumatic inflammatory diseases or conditions other than axSpA, e.g., rheumatoid arthritis, PsA, sarcoidosis, systemic lupus erythematosus, enteropathic or reactive arthritis.
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.
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.
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).
Participants with evidence of acute ocular inflammation, including active anterior uveitis (i.e., acute episode), within the last 4 weeks before the Baseline Visit.
Participants who have experienced a period of ≥3 weeks of unexplained diarrhea in the 24 weeks before the initiation of study treatment.
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.
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).
Participants with any current nontuberculous mycobacterial infection or any history of nontuberculous mycobacterial infection at Screening.
Participants with a concurrent acute or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at the Screening.
Participants with evidence of human immunodeficiency virus (HIV) infection at Screening.
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.
Participants with a history of a lymphoproliferative disorder 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 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.
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.
Participants who are unsuitable for IL-17A/IL-17F therapy according to the investigator’s discretion.
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.
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).
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.
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.
Participants who have a history of chronic alcohol or drug abuse in the past year before the Screening.
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.
For participants with biopsy samples taken: history of clinically relevant coagulation disorders or medication or known hypersensitivity against local anesthetics.
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.
Participants with previous exposure to anti-IL-17RA (e.g., brodalumab), and/or anti-IL- 17A/F therapies (e.g., bimekizumab), including sonelokimab.