Secukinumab for Giant Cell Arteritis and Polymyalgia Rheumatica

No longer recruiting at 43 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Novartis Pharmaceuticals

Disqualifiers: Pregnancy, Liver disease, Active infections, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 13

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the drug Secukinumab (also known as Cosentyx or AIN457) functions in the body and assesses its safety for individuals with giant cell arteritis (GCA) or polymyalgia rheumatica (PMR). The main goal is to understand the body's processing of the drug and ensure its tolerability after repeated use. Participants with active GCA, characterized by symptoms like sudden headaches or jaw pain, or PMR, marked by shoulder and hip pain, may be suitable for this trial. As a Phase 1 trial, the research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive it.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it does mention that you cannot use other investigational drugs within 5 half-lives of enrollment or within 30 days, whichever is longer. It's best to discuss your current medications with the trial investigators.

Is there any evidence suggesting that Secukinumab is likely to be safe for humans?

Research has shown that secukinumab is generally well-tolerated by people with polymyalgia rheumatica. Studies have found that it can provide long-lasting relief with fewer side effects than a placebo. For giant cell arteritis, secukinumab has also delivered promising results, with more participants experiencing lasting relief compared to a placebo. However, one study did not fully meet its primary goal for relief, resulting in mixed outcomes.

The FDA has already approved secukinumab for other conditions like psoriasis, indicating its well-established safety profile. In trials, common side effects include headaches or digestive issues, while serious problems are rare. Since this trial is in its early stages, the primary goal is to assess how the body handles the drug and ensure safety after multiple doses. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for GCA and PMR?

Researchers are excited about secukinumab for treating Giant Cell Arteritis (GCA) and Polymyalgia Rheumatica (PMR) because it offers a fresh approach compared to traditional treatments like corticosteroids and methotrexate. Most treatments for these conditions focus on broadly suppressing the immune system to reduce inflammation. However, secukinumab works uniquely by specifically targeting and blocking a protein called interleukin-17A (IL-17A), which plays a crucial role in the inflammatory process. This targeted action has the potential to reduce symptoms more effectively with fewer side effects than the current standard therapies.

What evidence suggests that Secukinumab might be an effective treatment for giant cell arteritis and polymyalgia rheumatica?

This trial will evaluate secukinumab for both polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). Research suggests that secukinumab could effectively treat PMR. In studies, patients taking secukinumab experienced significant and lasting symptom relief compared to those on a placebo, with symptoms improving and not quickly returning. For GCA, results are mixed. Some studies showed that secukinumab helped more patients achieve remission, especially those unresponsive to treatments like tocilizumab. However, other studies did not meet their primary goals for GCA. Overall, secukinumab shows promise, particularly for PMR. ^{1 3 4 6 7}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

Adults over 50 with Giant Cell Arteritis (GCA) or Polymyalgia Rheumatica (PMR), experiencing symptoms like severe headaches, vision loss, jaw pain when eating, and morning stiffness. Participants must have signs of active GCA not due to past damage and no other joint issues. They should also test negative for certain arthritis markers and show evidence of vasculitis on medical imaging or a temporal artery biopsy.

Inclusion Criteria

I was diagnosed with PMR less than 6 months ago and it is still active.

I am a man or a woman not pregnant or breastfeeding, and I am 50 years or older.

I am a man or a woman not pregnant or breastfeeding, and I am 50 years old or older.

Exclusion Criteria

For GCA: Pregnant or nursing women, history of hypersensitivity to study treatments, use of other investigational drugs within specified timeframes, clinically significant liver disease, active infections, active inflammatory bowel disease or uveitis, immuno-compromising diseases, severe progressive or uncontrolled diseases, confirmed diagnosis of any primary form of systemic vasculitis other than GCA

For PMR: Pregnant or nursing women, history of hypersensitivity to study treatments, use of other investigational drugs within specified timeframes, clinically significant liver disease, active infections, active inflammatory bowel disease or uveitis, immuno-compromising diseases, severe progressive or uncontrolled diseases, evidence of GCA, concurrent rheumatoid arthritis or other inflammatory arthritis, concurrent connective tissue diseases, concurrent neuropathic muscular diseases, inadequately treated hypothyroidism

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

6-8 weeks

1 visit (in-person)

Treatment

Participants receive 3 intravenous doses of Secukinumab over 12 weeks

12 weeks

3 visits (in-person at Week 0, Week 4, and Week 8)

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Visits at Weeks 9, 10, 11, 12, 16, and 20

What Are the Treatments Tested in This Trial?

Interventions

• Secukinumab

Trial Overview The trial is testing the safety and how well the body handles multiple doses of Secukinumab given through an IV in patients with GCA or PMR. It will track how the drug moves through and exits the body, as well as its tolerability after repeated infusions.

How Is the Trial Designed?

Group I: Secukinumab: Polymyalgia Rheumatica (PMR) Experimental Treatment 1 Intervention

Group II: Secukinumab: Giant Cell Arteritis (GCA) Experimental Treatment 1 Intervention

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

Approved in European Union as Cosentyx for:

• Moderate to severe plaque psoriasis
• Psoriatic arthritis
• Ankylosing spondylitis
• Non-radiographic axial spondyloarthritis

Approved in United States as Cosentyx for:

• Moderate to severe plaque psoriasis
• Psoriatic arthritis
• Ankylosing spondylitis
• Non-radiographic axial spondyloarthritis
• Hidradenitis suppurativa

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

Secukinumab 150 mg demonstrated significantly better clinical efficacy in treating active rheumatoid arthritis (RA) patients who did not respond adequately to TNF inhibitors, with notable improvements in ACR20, ACR50, and ACR70 response rates over 24 weeks.

There was no increased risk of adverse effects or serious adverse effects associated with secukinumab compared to placebo, indicating it is a safe therapeutic option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of secukinumab in active rheumatoid arthritis with an inadequate response to tumor necrosis factor inhibitors: a meta-analysis of phase III randomized controlled trials. Huang, Y., Fan, Y., Liu, Y., et al.[2020]

In a 52-week study involving 237 patients with rheumatoid arthritis, those treated with 150 mg of secukinumab showed sustained improvements in disease activity scores from Week 20 to Week 52, indicating its long-term efficacy.

The safety profile of secukinumab remained consistent over the study period, with a 64.8% rate of adverse events, mostly mild to moderate, and no deaths reported, suggesting it is a relatively safe option for patients who do not respond to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

One-year efficacy and safety results of secukinumab in patients with rheumatoid arthritis: phase II, dose-finding, double-blind, randomized, placebo-controlled study. Genovese, MC., Durez, P., Richards, HB., et al.[2019]

Secukinumab, while effective for treating moderate-to-severe psoriasis and psoriatic arthritis, has been associated with a range of adverse events of special interest (AESI) in over 1077 patients, with inflammatory bowel disease being the most common.

Most AESI reported were mild to moderate in severity and typically resolved after discontinuation of secukinumab, suggesting that while the drug is effective, healthcare providers should monitor for these potential side effects to ensure timely management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of secukinumab-induced adverse events of special interest and its potential pathogenesis. Liang, J., Zhang, S., Li, Q., et al.[2022]

In a phase 2 clinical trial involving 30 patients with giant cell arteritis, tocilizumab significantly improved the rate of complete remission at week 12 compared to placebo, with 85% of patients achieving remission versus 40% in the placebo group.

Tocilizumab also allowed for a quicker reduction in glucocorticoid use, with patients in the tocilizumab group stopping glucocorticoids 12 weeks earlier on average, leading to a much lower cumulative dose of prednisolone compared to the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tocilizumab for induction and maintenance of remission in giant cell arteritis: a phase 2, randomised, double-blind, placebo-controlled trial. Villiger, PM., Adler, S., Kuchen, S., et al.[2022]

This phase II study involves 50 patients with newly diagnosed or relapsing giant cell arteritis (GCA) to evaluate the efficacy and safety of secukinumab, an anti-IL-17A antibody, compared to placebo, alongside a prednisolone taper regimen.

The primary goal is to determine the proportion of patients achieving sustained remission by week 28, marking the first placebo-controlled assessment of secukinumab's effectiveness in GCA treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of secukinumab in patients with giant cell arteritis: study protocol for a randomized, parallel group, double-blind, placebo-controlled phase II trial. Venhoff, N., Schmidt, WA., Lamprecht, P., et al.[2021]

In a prospective trial involving 13 patients with giant cell arteritis (GCA), ustekinumab (UST) combined with a 24-week prednisone taper led to remission in all patients within 4 weeks, but only 23% achieved the primary endpoint of prednisone-free remission by week 52.

The study faced a high rate of treatment failure, with 77% of patients not meeting the primary endpoint, indicating that while UST may induce initial remission, its long-term efficacy in preventing relapse in GCA is limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ustekinumab for the Treatment of Giant Cell Arteritis. Matza, MA., Fernandes, AD., Stone, JH., et al.[2021]

Tocilizumab (TCZ) significantly reduces the relapse rate of giant cell arteritis (GCA) from 0.84 relapses per person-year before treatment to 0.28 relapses per person-year while on TCZ, indicating its efficacy in managing the condition.

The treatment is well tolerated, with only 14.9% of patients discontinuing due to adverse events of significant interest (AESIs), but over 50% of patients relapsed after stopping TCZ, suggesting the need for further research on the optimal duration of therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relapse Risk and Safety of Long-Term Tocilizumab Use Among Patients With Giant Cell Arteritis: A Single-Enterprise Cohort Study. Samec, MJ., Rakholiya, J., Langenfeld, H., et al.[2023]

In a 4-year study involving 48 Taiwanese patients with active ankylosing spondylitis, secukinumab 150mg showed sustained efficacy, with significant improvements in ASAS20/40 responses throughout the treatment period.

The safety profile of secukinumab remained consistent with previous studies, and no unexpected safety issues were reported, indicating it is a safe long-term treatment option for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Secukinumab Demonstrates Sustained Efficacy and Safety in a Taiwanese Subpopulation With Active Ankylosing Spondylitis: Four-Year Results From a Phase 3 Study, MEASURE 1. Tseng, JC., Wei, JC., Deodhar, A., et al.[2021]

Secukinumab, an IL-17 inhibitor, has shown significant efficacy and safety in treating psoriasis and psoriatic arthritis, based on results from seven phase III and five phase II clinical trials involving various patient populations.

The treatment led to rapid clinical improvement, with a favorable safety profile, where common side effects included nasopharyngitis and upper respiratory infections, indicating it is a promising option for patients who do not respond to existing therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Secukinumab in the Treatment of Psoriasis and Psoriatic Arthritis: A Review of the Literature. Abrouk, M., Gandy, J., Nakamura, M., et al.[2019]

Imaging techniques like color duplex sonography can effectively diagnose giant cell arteritis (GCA) without the need for a temporal artery biopsy, although their role in patient follow-up remains uncertain.

Recent studies indicate that biologics, particularly the interleukin-6 antagonist tocilizumab, can reduce glucocorticoid (GC) requirements and relapse rates in patients with GCA and polymyalgia rheumatica, suggesting a promising direction for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Management of polymyalgia rheumatica and large vessel vasculitis]. Hellmich, B.[2018]

The first treat-to-target (T2T) recommendations for managing giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) emphasize the importance of shared decision-making between patients and physicians, particularly for urgent treatment in GCA to prevent serious complications.

Key treatment targets include achieving and maintaining remission, preventing tissue damage, and considering comorbidities when assessing disease activity, highlighting a comprehensive approach to improving patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treat-to-target recommendations in giant cell arteritis and polymyalgia rheumatica. Dejaco, C., Kerschbaumer, A., Aletaha, D., et al.[2023]

A systematic review of 76 studies, including 31 randomized clinical trials, found that Treat to Target (T2T) strategies in Polymyalgia Rheumatica (PMR) primarily focused on managing glucocorticoid doses and tapering, while in Giant Cell Arteritis (GCA), the emphasis was on preventing relapses and achieving remission.

No studies directly compared T2T strategies to standard care, indicating a significant gap in research that could inform better treatment recommendations for PMR and GCA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence on treat to target strategies in polymyalgia rheumatica and giant cell arteritis: a systematic literature review. Hysa, E., Bond, M., Ehlers, L., et al.[2023]

In a phase 3 trial involving 161 patients with giant cell arteritis, sirukumab treatment led to a lower proportion of disease flares compared to placebo, suggesting it may be effective in managing the condition.

Despite the study being terminated early, sirukumab was generally well-tolerated, with no unexpected safety issues reported, although a high percentage of patients experienced treatment-emergent adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Multicentre, Randomised, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Sirukumab in the Treatment of Giant Cell Arteritis. Schmidt, WA., Dasgupta, B., Luqmani, R., et al.[2021]

Citations

1. novartis.com novartis.com/us-en/news/media-releases/novartis-provides-update-phase-iii-gcaptain-study-cosentyx-giant-cell-arteritis-gca

Novartis provides update on Phase III GCAptAIN study of ... The GCAptAIN study did not meet its primary endpoint of sustained remission at Week 52 in adults with newly diagnosed or relapsing GCA1 ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40366735/

Secukinumab is effective and safe for patients with giant ... Conclusions: Secukinumab demonstrated effectiveness in achieving clinical and imaging remission in patients with GCA failing tocilizumab. These ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0003496725011185

OP0062 Secukinumab in patients with giant cell arteritis ... Secukinumab treatment resulted in a higher sustained remission rate in GCA patients compared to placebo at week 28 (70% vs. 20%) with effects lasting 52 weeks ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04930094

NCT04930094 | Phase III Study of Efficacy and Safety ... This is a phase III study of efficacy and safety of secukinumab versus placebo, in combination with glucocorticoid taper regimen, in patients with giant cell ...

5. thelancet.com thelancet.com/journals/lanrhe/article/PIIS2665-9913(23)00101-7/abstract

Safety and efficacy of secukinumab in patients with giant ... Patients with active giant cell arteritis had a higher sustained remission rate in the secukinumab group than in the placebo group at week 28, in combination ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03765788

A Placebo-controlled Phase 2 Trial to Investigate the Safety ... This study was designed to evaluate the efficacy and safety of secukinumab compared to placebo to maintain disease remission up to 28 weeks.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8369438/

Efficacy and safety of secukinumab in patients with giant ... There is anecdotal evidence of successful induction and maintenance of remission with the monoclonal anti-IL-17A antibody secukinumab.