Ixekizumab + Tirzepatide for Psoriatic Arthritis

(TOGETHER-PsA Trial)

Recruiting at 94 trial locations

Overseen By Alan Kivitz

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

Must not be taking: Insulin, IL-17 inhibitors

Disqualifiers: T1DM, Obesity surgery, IBD, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: 13

250 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The main purpose of this study is to demonstrate that when participants with psoriatic arthritis and obesity or overweight in the presence of at least 1 weight-related comorbid condition receive ixekizumab and tirzepatide concomitantly administered, participants see improvement in their psoriatic arthritis and achieve weight reduction compared to when receiving ixekizumab. Participation in this study includes up to 12 visits and could last up to 61 weeks including screening, open label treatment period, and post-treatment follow-up period.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is the combination of Ixekizumab and Tirzepatide safe for humans?

Ixekizumab has been studied for safety in conditions like psoriatic arthritis and axial spondyloarthritis, showing it is generally safe for humans. However, there is no specific safety data available for the combination of Ixekizumab and Tirzepatide. ^{1 2 3 4 5}

How is the drug combination of Ixekizumab and Tirzepatide unique for treating psoriatic arthritis?

The combination of Ixekizumab and Tirzepatide is unique because Ixekizumab targets IL-17A, a protein involved in inflammation, while Tirzepatide is known for its role in managing blood sugar and weight, potentially offering a novel approach by addressing both inflammation and metabolic aspects of psoriatic arthritis. ^{1 2 6 7 8}

What data supports the effectiveness of the drug Ixekizumab for Psoriatic Arthritis?

Research shows that Ixekizumab is effective in improving joint symptoms and skin clearance in patients with psoriatic arthritis, with studies demonstrating its superiority over another drug, adalimumab, in achieving these improvements. ^{2 6 9 10 11}

Who Is on the Research Team?

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Are You a Good Fit for This Trial?

This trial is for adults with psoriatic arthritis who are also overweight or obese. Participants will visit the study site up to 12 times over a maximum of 61 weeks, including different phases like screening and follow-up.

Inclusion Criteria

I have active Psoriatic Arthritis with at least 3 tender and 3 swollen joints.

Have a body mass index (BMI) greater or equal to ≥27 kilograms per meter squared (kg/m²)

I have been diagnosed with Psoriatic Arthritis for at least 6 months.

Exclusion Criteria

I have used ixekizumab or tirzepatide before.

I had a bad reaction or no improvement with IL-17i or GLP-1 drugs.

I have had or am planning to have surgery for weight loss.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Open-label Treatment

Participants receive ixekizumab and tirzepatide concomitantly administered to improve psoriatic arthritis and achieve weight reduction

36 weeks

Up to 12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 21 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ixekizumab
• Tirzepatide

Trial Overview The trial tests if ixekizumab combined with tirzepatide helps improve psoriatic arthritis symptoms and aids in weight loss better than ixekizumab alone in participants with both conditions.

How Is the Trial Designed?

Group I: Ixekizumab and Tirzepatide Experimental Treatment 2 Interventions

Ixekizumab concomitantly administered with tirzepatide SC.

Group II: Ixekizumab Experimental Treatment 1 Intervention

Ixekizumab administered subcutaneous (SC).

Ixekizumab is already approved in United States, European Union for the following indications:

Approved in United States as Taltz for:

• Moderate-to-severe plaque psoriasis
• Active psoriatic arthritis
• Active ankylosing spondylitis
• Active non-radiographic axial spondyloarthritis

Approved in European Union as Taltz for:

• Moderate-to-severe plaque psoriasis
• Active psoriatic arthritis
• Active ankylosing spondylitis

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Published Research Related to This Trial

In a clinical trial involving biological disease-modifying antirheumatic drug-naïve patients with active psoriatic arthritis, ixekizumab (IXE) was found to be superior to adalimumab (ADA) in achieving significant improvements in both joint and skin disease at week 24, with 36% of IXE patients achieving the primary endpoint compared to 28% of ADA patients.

IXE also demonstrated a better safety profile, with serious adverse events reported in 3.5% of IXE patients compared to 8.5% in ADA patients, indicating that IXE may be a safer option for patients with inadequate response to conventional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A head-to-head comparison of the efficacy and safety of ixekizumab and adalimumab in biological-naïve patients with active psoriatic arthritis: 24-week results of a randomised, open-label, blinded-assessor trial. Mease, PJ., Smolen, JS., Behrens, F., et al.[2020]

In a phase III study involving 417 patients with psoriatic arthritis, ixekizumab (IXE) demonstrated sustained efficacy over 52 weeks, with ACR20 response rates of approximately 69% for both dosing regimens (every 2 weeks and every 4 weeks).

The safety profile of IXE was consistent with previous studies, showing minimal serious adverse events (0-4%) and no reported deaths, with common side effects including nasopharyngitis and injection site reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Ixekizumab in Patients with Active Psoriatic Arthritis: 52-week Results from a Phase III Study (SPIRIT-P1). van der Heijde, D., Gladman, DD., Kishimoto, M., et al.[2022]

In a study of 679 patients with psoriatic arthritis, ixekizumab treatment led to significantly higher rates of resolution for enthesitis (39% for IXEQ4W and 35% for IXEQ2W) and dactylitis (78% for IXEQ4W and 65% for IXEQ2W) compared to placebo (21% for enthesitis and 24% for dactylitis).

Resolution of enthesitis was linked to notable improvements in physical function and health-related quality of life, with patients experiencing a mean improvement in the Health Assessment Questionnaire-Disability Index (HAQ-DI) of -0.44 for those who resolved enthesitis, compared to -0.25 for those who did not.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ixekizumab and complete resolution of enthesitis and dactylitis: integrated analysis of two phase 3 randomized trials in psoriatic arthritis. Gladman, DD., Orbai, AM., Klitz, U., et al.[2020]

In the SPIRIT-H2H trial, ixekizumab was found to be significantly more effective than adalimumab in achieving both joint symptom improvement (ACR50) and complete skin clearance (PASI100) in patients with psoriatic arthritis and moderate-to-severe psoriasis, with results maintained through 52 weeks.

Patients treated with ixekizumab also showed higher rates of nail psoriasis clearance and reported a better quality of life, with no new safety concerns identified during the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Ixekizumab Versus Adalimumab in Biologic-naïve Patients With Active Psoriatic Arthritis and Moderate-to-severe Psoriasis: 52-week Results From the Randomized SPIRIT-H2H Trial. Reich, K., Kristensen, LE., Smith, SD., et al.[2022]

In a real-world study of 89 adult patients with psoriatic arthritis (PsA) treated with ixekizumab (IXE), the treatment showed high persistence rates of 95.5% at 24 weeks and 68.5% at 104 weeks, indicating that most patients continued their therapy without discontinuation.

Patients experienced significant improvements in disease activity, as measured by the Disease Activity in Psoriatic Arthritis (DAPSA) scores, which decreased from an average of 23.7 at baseline to 14.3 at 24 weeks, suggesting that IXE is an effective treatment option for managing PsA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Persistence and Use of Ixekizumab in Patients with Psoriatic Arthritis in Real-World Practice in Spain. The PRO-STIP Study. Joven, B., Hernández Sánchez, R., Pérez-Pampín, E., et al.[2023]

Ixekizumab, a monoclonal antibody targeting IL-17A, showed a higher risk of injection site reactions compared to placebo and adalimumab, with rates of up to 25.3%, but had significantly fewer serious adverse events than adalimumab in patients with psoriatic arthritis (PsA).

In terms of efficacy, ixekizumab was found to be as effective as adalimumab across various PsA disease activity domains and outperformed it in psoriasis outcomes, indicating its potential as a strong treatment option for PsA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ixekizumab for Psoriatic Arthritis: Safety, Efficacy, and Patient Selection. Miller, J., Puravath, AP., Orbai, AM.[2022]

In a study involving 1,118 patients with psoriatic arthritis, ixekizumab was associated with a higher frequency of treatment-emergent adverse events (68.1%) compared to placebo (56.7%), but no unexpected safety outcomes were reported.

Common side effects included injection site reactions (21.4% for ixekizumab vs. 4.5% for placebo) and non-serious hypersensitivities (5.3% for ixekizumab vs. 1.8% for placebo), while serious infections were low (1.3% for ixekizumab) and no cases of active tuberculosis or major adverse cardiac events were observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Ixekizumab in Patients With Psoriatic Arthritis: Results From a Pooled Analysis of Three Clinical Trials. Mease, P., Roussou, E., Burmester, GR., et al.[2020]

In a study involving 932 patients with axial spondyloarthritis treated with ixekizumab for up to 116 weeks, 64.9% of patients with radiographic axSpA and 57.7% with non-radiographic axSpA achieved significant improvement (ASAS40) by week 116, indicating sustained efficacy.

The safety profile of ixekizumab remained consistent with previous studies, with no new safety concerns identified, suggesting it is a safe long-term treatment option for patients with axSpA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ixekizumab treatment in patients with axial spondyloarthritis: 2-year results from COAST. Braun, J., Kiltz, U., Deodhar, A., et al.[2022]

In a post hoc analysis of the SPIRIT-P1 trial involving patients with severe psoriatic arthritis, ixekizumab significantly improved joint and skin symptoms compared to placebo, with 63.3% of patients on ixekizumab Q4W achieving a 20% improvement (ACR 20) versus only 24.5% on placebo.

The safety profile of ixekizumab in this severe population was consistent with previous findings, indicating no new safety concerns, which supports its use as an effective treatment option for severe psoriatic arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ixekizumab Efficacy in Patients with Severe Peripheral Psoriatic Arthritis: A Post Hoc Analysis of a Phase 3, Randomized, Double-Blind, Placebo-Controlled Study (SPIRIT-P1). Kameda, H., Hagimori, K., Morisaki, Y., et al.[2023]

Ixekizumab is a humanized monoclonal antibody specifically designed to inhibit interleukin-17A (IL-17A), a key cytokine involved in inflammatory conditions, making it a targeted treatment for plaque psoriasis.

The approval of ixekizumab in the USA marks a significant milestone in its development, highlighting its efficacy in managing plaque psoriasis by reducing inflammation associated with the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ixekizumab: First Global Approval. Markham, A.[2018]

In a study of 12 Japanese patients with generalized pustular psoriasis (GPP) and erythrodermic psoriasis (EP), ixekizumab demonstrated efficacy, with 57% of GPP patients and 20% of EP patients achieving 'resolved' or 'improved' status by Week 12.

The treatment was found to be safe, with only one non-drug related serious adverse event reported and no adverse events from Week 12 to Week 20 in GPP patients, indicating a favorable safety profile for continuous dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ixekizumab 80 mg Every 2 Weeks Treatment Beyond Week 12 for Japanese Patients with Generalized Pustular Psoriasis and Erythrodermic Psoriasis. Morita, A., Okubo, Y., Morisaki, Y., et al.[2022]

Citations

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

A head-to-head comparison of the efficacy and safety of ixekizumab and adalimumab in biological-naïve patients with active psoriatic arthritis: 24-week results of a randomised, open-label, blinded-assessor trial. [2020]

2. Canada pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Ixekizumab in Patients with Active Psoriatic Arthritis: 52-week Results from a Phase III Study (SPIRIT-P1). [2022]

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

Ixekizumab and complete resolution of enthesitis and dactylitis: integrated analysis of two phase 3 randomized trials in psoriatic arthritis. [2020]

4. Austria pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Ixekizumab Versus Adalimumab in Biologic-naïve Patients With Active Psoriatic Arthritis and Moderate-to-severe Psoriasis: 52-week Results From the Randomized SPIRIT-H2H Trial. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Persistence and Use of Ixekizumab in Patients with Psoriatic Arthritis in Real-World Practice in Spain. The PRO-STIP Study. [2023]

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

Ixekizumab for Psoriatic Arthritis: Safety, Efficacy, and Patient Selection. [2022]

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

Safety of Ixekizumab in Patients With Psoriatic Arthritis: Results From a Pooled Analysis of Three Clinical Trials. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ixekizumab treatment in patients with axial spondyloarthritis: 2-year results from COAST. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Ixekizumab Efficacy in Patients with Severe Peripheral Psoriatic Arthritis: A Post Hoc Analysis of a Phase 3, Randomized, Double-Blind, Placebo-Controlled Study (SPIRIT-P1). [2023]

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

Ixekizumab: First Global Approval. [2018]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Ixekizumab 80 mg Every 2 Weeks Treatment Beyond Week 12 for Japanese Patients with Generalized Pustular Psoriasis and Erythrodermic Psoriasis. [2022]