Ixekizumab + Tirzepatide for Psoriasis

(TOGETHER-PsO Trial)

Not currently recruiting at 76 trial locations

Overseen By Howard Sofen

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, Cancer, 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: 12

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two medications, ixekizumab (a monoclonal antibody) and tirzepatide (a GIP/GLP-1 receptor agonist), to determine their effectiveness in improving plaque psoriasis and aiding weight loss. It targets individuals who have had moderate to severe plaque psoriasis for at least six months and are either overweight or obese with a related health condition, such as high blood pressure or diabetes. Participants will attend up to 12 visits over approximately a year. The study compares those taking both medications to those taking only ixekizumab. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ixekizumab is generally safe for adults with moderate to severe plaque psoriasis. Long-term studies indicate it can be used safely for up to five years, though some individuals might experience side effects, such as an increased risk of infections.

Tirzepatide, a newer treatment approved for other conditions, has been found safe in studies for those uses, with most side effects being mild, such as stomach upset.

Early research suggests that using ixekizumab and tirzepatide together can improve psoriasis and aid in weight loss. While safety information for this combination is still being collected, each treatment has demonstrated safety when used individually. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining Ixekizumab and Tirzepatide for psoriasis because this treatment may offer a dual approach that stands out from current options like topical steroids or biologics targeting specific immune pathways. Ixekizumab is already known for its effectiveness in targeting the interleukin-17A pathway, which plays a key role in psoriasis. Tirzepatide, typically used for diabetes, introduces a novel mechanism by acting on the GLP-1 and GIP receptors, potentially addressing metabolic components linked with psoriasis. This combination might not only tackle the skin symptoms but also the underlying metabolic issues, offering a comprehensive treatment approach.

What evidence suggests that this trial's treatments could be effective for psoriasis?

Research has shown that ixekizumab, one of the treatments in this trial, effectively treats psoriasis. In one study, 94.3% of patients experienced at least a 75% improvement in their psoriasis. Additionally, 85.1% of patients achieved a 90% improvement, and 71.8% saw their psoriasis completely clear up.

This trial will also test a combination of ixekizumab and tirzepatide. Studies suggest that this combination may improve psoriasis and aid in weight loss. Early evidence indicates this combination could be particularly beneficial for individuals who are overweight or have diabetes, as it addresses both skin issues and weight concerns simultaneously. ^{1 6 7 8 9}

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 moderate-to-severe plaque psoriasis who are also overweight or obese. Participants should be interested in improving their skin condition and reducing weight. Specific eligibility criteria details were not provided, so it's important to contact the study organizers for more information.

Inclusion Criteria

Over 10% of my body is affected.

Have a body mass index (BMI) of ≥27 kilograms per meter squared (kg/m²)

My psoriasis is severe, with a sPGA score of 3 or more and a PASI score of 12 or more.

Exclusion Criteria

I have Type 1 Diabetes.

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

I have Type 2 Diabetes and take insulin.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Open-label Treatment

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

36 weeks

Up to 12 visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

21 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ixekizumab
• Tirzepatide

Trial Overview The study tests if taking Ixekizumab together with Tirzepatide helps improve psoriasis and supports weight loss better than just Ixekizumab alone. The trial involves up to 12 visits over a maximum of 61 weeks, including treatment and follow-up periods.

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 study involving 83 healthy adults, ixekizumab (IXE) was found to be noninferior to a control in terms of immune response to tetanus and pneumococcal vaccines, indicating it does not hinder the effectiveness of these vaccines.

IXE was well tolerated, with only mild treatment-emergent adverse events reported, suggesting it is a safe option for patients receiving vaccinations while on this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response to Tetanus and Pneumococcal Vaccination Following Administration of Ixekizumab in Healthy Participants. Gomez, EV., Bishop, JL., Jackson, K., et al.[2018]

In a study of 91 Japanese patients with moderate-to-severe psoriasis, ixekizumab demonstrated rapid improvements in skin clearance and quality of life, with significant enhancements in the Dermatology Life Quality Index (DLQI) and Itch Numeric Rating Scale (NRS) at weeks 4 and 12.

Patients who achieved complete skin clearance (PASI 100) by week 4 or 12 experienced better outcomes in itch relief, indicating that faster responses to treatment are crucial for improving overall patient well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationship Between Rapid Skin Clearance and Quality of Life Benefit: Post Hoc Analysis of Japanese Patients with Moderate-to-Severe Psoriasis Treated with Ixekizumab (UNCOVER-J). Honma, M., Cai, Z., Burge, R., et al.[2020]

In a study of 136 psoriasis patients treated with ixekizumab over 6 months, significant improvements were observed in disease severity, with a mean decrease in the Investigator Global Assessment (IGA*BSA) score of -45.5 and a body surface area (BSA) reduction of -12.4.

A high percentage of patients achieved significant treatment milestones, including 84.6% reaching an absolute Psoriasis Area and Severity Index (PASI) score of ≤ 5, indicating effective management of psoriasis symptoms across various patient groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Disease response and patient-reported outcomes among initiators of ixekizumab. Shahriari, M., Harrison, RW., Burge, R., et al.[2022]

Ixekizumab is a highly effective monoclonal antibody that targets IL-17A, showing rapid results and favorable long-term outcomes in treating moderate-to-severe psoriasis, as supported by Phase III trials and real-life data.

The safety profile of ixekizumab is considered adequate, making it a viable treatment option for both adults and children with psoriasis, psoriatic arthritis, and axial spondyloarthropathies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ixekizumab for the treatment of moderate-to-severe plaque psoriasis: the first septennium. Carmona-Rocha, E., Puig, L.[2023]

In a study involving 6892 adult patients with moderate-to-severe psoriasis, ixekizumab demonstrated a long-term safety profile with low incidence rates of serious adverse events (5.4 per 100 patient-years) and serious infections (1.3 per 100 patient-years) over a cumulative exposure of 18,025.7 patient-years.

No new or unexpected safety events were reported, with the incidence rates for major adverse cerebro-cardiovascular events and inflammatory bowel disease remaining low, indicating that ixekizumab is a safe treatment option for psoriasis over extended periods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Ixekizumab in Adult Patients with Moderate-to-Severe Psoriasis: Data from 17 Clinical Trials with Over 18,000 Patient-Years of Exposure. Griffiths, CEM., Gooderham, M., Colombel, JF., et al.[2022]

A case study of a 51-year-old woman treated with ixekizumab for plaque psoriasis revealed a rare instance of varicella zoster virus (VZV) reactivation, leading to meningoradiculitis and cerebral venous thrombosis, suggesting a potential risk of viral reactivation during treatment with this IL-17 inhibitor.

Despite the reported safety profile of ixekizumab, this case highlights the need for vigilance regarding neurological complications from VZV, even in the absence of skin lesions, and emphasizes the importance of PCR testing of cerebrospinal fluid for accurate diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meningoradiculitis due to varicella zoster virus reactivation in a patient treated with ixekizumab. Dubois, M., Morel, G., Tone, A., et al.[2021]

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 198 patients with moderate-to-severe plaque psoriasis treated with ixekizumab for 24 months, 94.3% achieved a 75% improvement in psoriasis severity (PASI75), demonstrating its long-term effectiveness.

Patients began to see improvements as early as 4 weeks after starting treatment, with significant enhancements in quality of life noted by Week 12, indicating that ixekizumab not only reduces symptoms but also positively impacts overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ixekizumab is effective in the long-term management in moderate-to-severe plaque psoriasis: results from an Italian retrospective cohort study (the LOTIXE study). Chiricozzi, A., Megna, M., Giunta, A., et al.[2023]

In phase 3 UNCOVER trials, ixekizumab was found to be significantly more effective than placebo and etanercept in treating moderate to severe plaque psoriasis, with patients showing a ≥75% reduction in psoriasis severity within 12 weeks.

Ixekizumab was generally well tolerated, with low immunogenicity and sustained clinical responses over 60 weeks, making it a promising treatment option that requires only one maintenance dose every 4 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ixekizumab: A Review in Moderate to Severe Plaque Psoriasis. Syed, YY.[2017]

In a phase III trial involving 1,227 patients with moderate-to-severe plaque psoriasis, continuous dosing of ixekizumab every 2 weeks (Q2W) for 52 weeks showed significantly higher efficacy compared to every 4 weeks (Q4W), with 85.9% achieving a 75% improvement in psoriasis severity versus 79.0% for Q4W.

Both dosing regimens had comparable safety profiles, indicating that the increased efficacy of the Q2W regimen did not come with a higher risk of treatment-emergent or serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of continuous every-2-week dosing of ixekizumab over 52 weeks in patients with moderate-to-severe plaque psoriasis in a randomized phase III trial (IXORA-P). Langley, RG., Papp, K., Gooderham, M., et al.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37434099/

Data from the United States Taltz Customer Support Program Patient-reported improvements in BSA, itch, skin pain, dermatology-specific quality of life, and overall PsO severity were seen as early as 2 weeks after ...

2. taltz.lilly.com taltz.lilly.com/hcp/dermatology/adult-psoriasis

Adult Psoriasis (PsO) - Taltz - Eli Lilly Ixekizumab results in persistent clinical improvement in moderate-to-severe genital psoriasis during a 52 week, randomized, placebo-controlled, phase 3 clinical ...

3. mdpi.com mdpi.com/2077-0383/14/3/833

Comparative Analysis of Ixekizumab Effectiveness with and ... Among anti-IL-17 agents, ixekizumab showed promising results with a 4-year drug survival rate of 82.6%, second only to risankizumab. Stratified analysis ...

4. tandfonline.com tandfonline.com/doi/full/10.1080/09546634.2023.2246606

Full article: Ixekizumab is effective in the long-term ... At Month 24, 94.3% of patients achieved PASI75 response, while 85.1 and 71.8% achieved PASI90 and PASI100, respectively; and 91.1% of the ...

5. link.springer.com link.springer.com/article/10.1007/s12325-025-03258-9

Real-World Evidence for Ixekizumab in the Treatment of ... In the real-world setting, ixekizumab was shown to have a positive impact on patient quality of life and generally high levels of persistence ...

6. arthritis-research.biomedcentral.com arthritis-research.biomedcentral.com/articles/10.1186/s13075-023-03257-7

Long-term safety of Ixekizumab in adults with psoriasis ... Here, we present the final, end-of-study program update, examining integrated safety data, following long-term IXE treatment in adult patients ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9209552/

Safety of Ixekizumab in Adult Patients with Moderate-to ... We report a comprehensive summary of the safety outcomes in adult patients with moderate-to-severe psoriasis with up to 5 years of exposure to ixekizumab.

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/125521s014lbl.pdf

Taltz - accessdata.fda.gov Overall, the safety profile observed in patients with psoriatic arthritis treated with TALTZ Q4W is consistent with the safety profile in adult patients with ...

9. taltz.lilly.com taltz.lilly.com/hcp/rheumatology/psoriatic-arthritis

Efficacy and Safety in PsA Treatment | Taltz® (ixekizumab) Taltz may increase the risk of infection. Serious infections have occurred. In clinical trials of adult patients with plaque psoriasis, the Taltz group had a ...