Sonelokimab for Psoriatic Arthritis

(IZAR-2 Trial)

Recruiting at 8 trial locations

Overseen By Moonlake Clinical Trial Helpdesk

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: MoonLake Immunotherapeutics AG

Must be taking: TNFα inhibitors

Must not be taking: Biologic immunomodulators

Disqualifiers: Chronic inflammatory conditions, IBD, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

600 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a study to confirm the clinical efficacy and safety of sonelokimab compared with placebo in the treatment of adults with active psoriatic arthritis who have had a previous inadequate response or intolerance to anti-tumor necrosis factor (TNF)α therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants must have had an inadequate response or intolerance to anti-TNFα therapy, which suggests that you may need to have tried and not responded well to certain medications before joining.

What evidence supports the effectiveness of the drug Sonelokimab for treating psoriatic arthritis?

Sonelokimab, which targets both IL-17A and IL-17F, has shown promising results in early studies for psoriasis, and similar drugs like bimekizumab have demonstrated effectiveness in treating psoriatic arthritis by targeting these same proteins. This suggests that Sonelokimab could potentially be effective for psoriatic arthritis as well. ^{1 2 3 4 5}

What is known about the safety of Sonelokimab for human use?

Sonelokimab has been studied in phase I and II trials for psoriasis, showing promising safety results. These studies suggest it is generally safe for human use, although more research is needed to confirm its safety across different conditions. ^{1 2 4 6 7}

What makes the drug Sonelokimab unique for treating psoriatic arthritis?

Sonelokimab is unique because it is a trivalent nanobody that targets both IL-17A and IL-17F, which are proteins involved in inflammation, potentially offering better disease control compared to treatments that target only one of these proteins. ^{2 4 6 8 9}

Eligibility Criteria

This trial is for adults over 18 with active psoriatic arthritis and plaque psoriasis who haven't responded well to or can't tolerate TNFα inhibitors. They must have at least 3 tender and swollen joints, not have rheumatoid arthritis markers, and meet specific diagnostic criteria.

Inclusion Criteria

I have tried 1 or 2 TNFα inhibitors for my PsA or PsO without success or stopped due to side effects.

I have been diagnosed with psoriatic arthritis for at least 6 months.

I tested negative for rheumatoid arthritis markers.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Participants receive an induction regimen of 4 doses of sonelokimab or placebo

8 weeks

4 visits (in-person)

Maintenance Treatment

Participants receive maintenance dosing of sonelokimab or placebo every 4 weeks starting at Week 8

8 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Sonelokimab

Trial Overview The study tests the effectiveness of Sonelokimab against a placebo in those unresponsive to anti-TNFα treatments. It aims to confirm if Sonelokimab is safe and works better for managing symptoms of psoriatic arthritis.

Participant Groups

Group I: sonelokimab dose 2 with an induction regimen Experimental Treatment 1 Intervention

Subjects randomized to this arm will receive sonelokimab dose 2 SC as an induction regimen of 4 doses, followed by sonelokimab SC Q4W maintenance dosing starting at Week 8.

Group II: sonelokimab dose 1 with an induction regimen Experimental Treatment 1 Intervention

Subjects randomized to this arm will receive sonelokimab dose 1 subcutaneously (SC) as an induction regimen of 4 doses , followed by sonelokimab SC every 4 weeks (Q4W) maintenance dosing starting at Week 8.

Group III: risankizumab Active Control 1 Intervention

Subjects randomized to this arm will receive risankizumab SC

Group IV: Placebo Placebo Group 1 Intervention

Subjects randomized to this arm will receive placebo SC

Who Is Running the Clinical Trial?

MoonLake Immunotherapeutics AG

Lead Sponsor

Trials

7

Recruited

2,800+

Findings from Research

In a phase III trial with 417 patients suffering from active psoriatic arthritis, ixekizumab significantly improved disease activity, with 62.1% of patients on the 80 mg every 2 weeks regimen achieving an ACR20 response compared to only 30.2% in the placebo group.

While ixekizumab showed efficacy in reducing disease symptoms and preventing structural damage, it also had a higher rate of treatment-emergent adverse events (65.7-66.4%) compared to placebo (47.2%), indicating a need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo-controlled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1. Mease, PJ., van der Heijde, D., Ritchlin, CT., et al.[2022]

In a phase 2b study involving 206 patients with active psoriatic arthritis, bimekizumab significantly improved symptoms compared to placebo, with higher response rates observed in the 16 mg and 160 mg dosage groups.

The safety profile of bimekizumab was acceptable, with most adverse events being mild or moderate, and no serious complications like deaths or inflammatory bowel disease reported, supporting further investigation in phase 3 trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bimekizumab in patients with active psoriatic arthritis: results from a 48-week, randomised, double-blind, placebo-controlled, dose-ranging phase 2b trial. Ritchlin, CT., Kavanaugh, A., Merola, JF., et al.[2020]

In a study of 42 patients with active psoriatic arthritis, secukinumab showed greater clinical responses and improvements in quality of life compared to placebo, particularly at weeks 12 and 24, despite not meeting the primary endpoint at week 6.

The safety profile of secukinumab was comparable to placebo, with a similar frequency of adverse events, indicating that it is a safe option for patients with psoriatic arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of secukinumab, a fully human anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe psoriatic arthritis: a 24-week, randomised, double-blind, placebo-controlled, phase II proof-of-concept trial. McInnes, IB., Sieper, J., Braun, J., et al.[2022]

Bimekizumab, a dual inhibitor targeting both IL-17A and IL-17F, has shown efficacy and safety in treating psoriasis and psoriatic arthritis across multiple phases of clinical trials (I, II, and III).

Sonelokimab, a trivalent nanobody also targeting IL-17A and IL-17F, has demonstrated promising results in early phase studies for psoriasis, indicating potential for effective treatment options in these chronic immune-mediated disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual inhibition of IL-17A and IL-17F in psoriatic disease. Iznardo, H., Puig, L.[2021]

Bimekizumab, a dual inhibitor antibody targeting both IL-17A and IL-17F, shows promising results in treating psoriatic arthritis, outperforming both placebo and treatments that inhibit IL-17A alone, based on a Phase 2b trial.

Early data from open-label extensions indicate that bimekizumab is safe and maintains its effectiveness, with Phase III trials currently underway to further evaluate its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Overview of Bimekizumab for the Treatment of Psoriatic Arthritis: The Evidence so Far. Oliveira, DG., Faria, R., Torres, T.[2023]

In a phase 2b trial involving 313 participants with moderate to severe plaque-type psoriasis, sonelokimab demonstrated significant efficacy, with 48.1% of patients in the 30 mg group and up to 88.2% in the 120 mg augmented load group achieving clear or almost clear skin (IGA score of 0 or 1) at week 12, compared to 0% in the placebo group.

Sonelokimab exhibited a safety profile comparable to secukinumab, with mostly mild to moderate adverse events, and a notable incidence of manageable Candida infections in the sonelokimab group, indicating it is a safe treatment option for psoriasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IL17A/F nanobody sonelokimab in patients with plaque psoriasis: a multicentre, randomised, placebo-controlled, phase 2b study. Papp, KA., Weinberg, MA., Morris, A., et al.[2022]

Brodalumab, an IL-17 antagonist approved for moderate-to-severe plaque psoriasis, has a safety profile similar to other IL-17 treatments, based on data from phase II and III clinical trials.

While common adverse events include nasopharyngitis and upper respiratory infections, a significant concern arose from six reported suicides among patients, leading to a black box warning, although no direct causal link was established.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brodalumab: A Review of Safety. Rusta-Sallehy, S., Gooderham, M., Papp, K.[2019]

Secukinumab, a monoclonal antibody targeting interleukin-17A, has shown strong efficacy in treating moderate to severe psoriasis, psoriatic arthritis, and ankylosing spondylitis, with a favorable safety profile based on data from 2800 patients in the SERENA study.

The SERENA study, which includes patients who have been on secukinumab for an average of one year, aims to provide insights into the long-term effectiveness and safety of the treatment in real-world settings, confirming that the baseline demographics align with existing literature.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Secukinumab Use in Patients with Moderate to Severe Psoriasis, Psoriatic Arthritis and Ankylosing Spondylitis in Real-World Setting in Europe: Baseline Data from SERENA Study. Kiltz, U., Sfikakis, PP., Gaffney, K., et al.[2021]

In a study involving 1414 patients with psoriatic arthritis (PsA) and 1164 patients with ankylosing spondylitis (AS), secukinumab demonstrated a very low incidence of treatment-emergent antidrug antibodies (TE-ADA), with only 0.35% in PsA and 0.69% in AS patients, indicating good immunogenicity safety.

The presence of TE-ADA did not affect the pharmacokinetics or efficacy of secukinumab, suggesting that the treatment remains effective even in patients who develop these antibodies, and no adverse events were linked to TE-ADA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Secukinumab Immunogenicity over 52 Weeks in Patients with Psoriatic Arthritis and Ankylosing Spondylitis. Deodhar, A., Gladman, DD., McInnes, IB., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo-controlled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Bimekizumab in patients with active psoriatic arthritis: results from a 48-week, randomised, double-blind, placebo-controlled, dose-ranging phase 2b trial. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of secukinumab, a fully human anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe psoriatic arthritis: a 24-week, randomised, double-blind, placebo-controlled, phase II proof-of-concept trial. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Dual inhibition of IL-17A and IL-17F in psoriatic disease. [2021]

5. New Zealand pubmed.ncbi.nlm.nih.gov

An Overview of Bimekizumab for the Treatment of Psoriatic Arthritis: The Evidence so Far. [2023]

6. England pubmed.ncbi.nlm.nih.gov

IL17A/F nanobody sonelokimab in patients with plaque psoriasis: a multicentre, randomised, placebo-controlled, phase 2b study. [2022]

7. Canada pubmed.ncbi.nlm.nih.gov

Brodalumab: A Review of Safety. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Secukinumab Use in Patients with Moderate to Severe Psoriasis, Psoriatic Arthritis and Ankylosing Spondylitis in Real-World Setting in Europe: Baseline Data from SERENA Study. [2021]

9. Canada pubmed.ncbi.nlm.nih.gov

Secukinumab Immunogenicity over 52 Weeks in Patients with Psoriatic Arthritis and Ankylosing Spondylitis. [2022]