Secukinumab for Polymyalgia Rheumatica

(REPLENISH Trial)

Not currently recruiting at 184 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Must be taking: Prednisone

Must not be taking: IL-6 inhibitors

Disqualifiers: Rheumatoid arthritis, Lupus, 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

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

Compensation: Varies

Number of Visits: 4

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called secukinumab for individuals with polymyalgia rheumatica (PMR), a condition causing shoulder and hip pain and stiffness. The study aims to determine if secukinumab, administered with a steroid called prednisone, is safe and effective for those who have recently experienced a PMR symptom flare-up. Participants will receive either a high dose, a low dose, or a placebo (a harmless pill resembling the real treatment) to compare results. Ideal candidates are adults over 50 whose PMR symptoms returned after reducing their prednisone dosage. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to the potential availability of a new treatment for PMR.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must be on prednisone between 7.5 mg/day and 25 mg/day at screening. If you are taking tocilizumab or similar medications, you must stop them at least 12 weeks before the study.

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

Research shows that secukinumab is generally well-tolerated. It significantly helps patients with polymyalgia rheumatica (PMR) feel better and have fewer symptoms compared to those who took a placebo. This suggests that secukinumab can help patients achieve remission, relieving symptoms. Patients with giant cell arteritis also experienced good results, showing a higher rate of lasting symptom relief.

While the treatment appears effective, any medication can have side effects. The studies reported no major safety concerns, suggesting that secukinumab is safe for many people. However, individual experiences can vary, so discussing any concerns with a healthcare provider is always advisable. ^{1 2 3 4 5}

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

Researchers are excited about Secukinumab for polymyalgia rheumatica because it offers a novel approach compared to traditional treatments like corticosteroids. Secukinumab is a biologic that works by targeting and inhibiting interleukin-17A, a protein involved in inflammatory responses, which sets it apart from typical steroid-based therapies. This targeted action has the potential to reduce inflammation with possibly fewer side effects, providing a promising alternative for patients who struggle with the long-term use of steroids. Additionally, with dosing options of both 150 mg and 300 mg every four weeks, it offers flexibility in treatment, which could improve patient outcomes and adherence.

What evidence suggests that secukinumab might be an effective treatment for polymyalgia rheumatica?

Research shows that secukinumab may help treat polymyalgia rheumatica (PMR). This trial will randomize participants to receive either secukinumab at 300 mg, secukinumab at 150 mg, or a placebo. Previous studies found that patients taking secukinumab felt significantly better compared to those taking a placebo, which contains no active medicine. More people improved and maintained their improvement with secukinumab. It also helped patients control their symptoms for a longer time. These results suggest that secukinumab could be a good option for managing PMR symptoms. ^{1 2 3 4 6}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

Adults over 50 with Polymyalgia Rheumatica (PMR) who've relapsed after trying to reduce their prednisone dosage can join. They must have been on prednisone for at least 8 weeks before and had a PMR flare-up while tapering off the drug within the last 12 weeks.

Inclusion Criteria

You have been diagnosed with polymyalgia rheumatica using specific guidelines from the American College of Rheumatology and the European League Against Rheumatism.

I am taking a steroid medication for my condition, between 7.5 and 25 mg/day.

I had a PMR flare-up while reducing my prednisone dose to 5 mg/day or more in the last 3 months.

Exclusion Criteria

I have a condition like rheumatoid arthritis or lupus.

My underactive thyroid is not properly managed.

I have been treated with drugs targeting IL-17 for my condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

up to 6 weeks

Treatment

Participants receive secukinumab or placebo subcutaneously for 52 weeks, with prednisone tapered over 24 weeks

52 weeks

Weekly visits for the first 4 weeks, then every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 24 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo to Secukinumab
• Secukinumab

Trial Overview The trial is testing Secukinumab, given as an injection under the skin, in two different doses (300 mg and 150 mg), compared to a placebo. All treatments are combined with a decreasing dose of prednisone over half a year.

How Is the Trial Designed?

Group I: Secukinumab 300 mg Experimental Treatment 1 Intervention

randomized in 1:1:1 ratio every 4 weeks

Group II: Secukinumab 150 mg Experimental Treatment 1 Intervention

randomized in 1:1:1 ratio every 4 weeks

Group III: Placebo to secukinumab Placebo Group 1 Intervention

randomized in 1:1:1 ratio every 4 weeks

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 is a newly approved interleukin-17 (IL-17) inhibitor that effectively targets and blocks the proinflammatory cytokine IL-17A, which is involved in autoimmune diseases like rheumatoid arthritis and psoriatic arthritis.

This biologic treatment has shown promise in reducing inflammation and disease progression in moderate-to-severe cases of plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis, marking a significant advancement in the management of these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Secukinumab for rheumatology: development and its potential place in therapy. Koenders, MI., van den Berg, WB.[2019]

Secukinumab, a monoclonal antibody targeting IL-17A, has been shown to significantly improve symptoms of psoriatic arthritis (PsA) in patients who have not responded to previous treatments, with benefits maintained for up to 5 years.

In clinical trials, secukinumab effectively inhibited structural joint damage and improved physical function and quality of life, demonstrating its safety and efficacy as a treatment option for active PsA compared to traditional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Secukinumab: A Review in Psoriatic Arthritis. Blair, HA.[2021]

Secukinumab, a monoclonal antibody targeting IL-17A, has shown significant efficacy in improving symptoms of psoriatic arthritis in Phase III clinical trials, even in patients who had previously not responded to other treatments like NSAIDs or DMARDs.

The treatment is generally well tolerated, with mild to moderate infections being the most common side effects, making it a viable alternative to existing therapies such as tumor necrosis factor inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Secukinumab: A Review in Psoriatic Arthritis. Shirley, M., Scott, LJ.[2019]

In a phase III study involving patients with rheumatoid arthritis who did not respond to TNF-α inhibitors, secukinumab did not show statistically significant improvements in ACR20 response rates compared to placebo at week 24.

The study confirmed the safety of secukinumab, with no new adverse events reported, but suggested that it may not offer additional benefits over existing second-line therapies for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Secukinumab after anti-tumour necrosis factor-α therapy: a phase III study in active rheumatoid arthritis. Dokoupilová, E., Aelion, J., Takeuchi, T., et al.[2019]

Secukinumab is an effective treatment for psoriatic arthritis (PsA), showing improvements in skin symptoms, enthesitis, dactylitis, and preventing the progression of joint damage, based on clinical studies.

The treatment is generally well tolerated, with common side effects including nasopharyngitis, headache, and upper respiratory infections, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Secukinumab for the treatment of psoriatic arthritis. Baronaite Hansen, R., Kavanaugh, A.[2019]

Secukinumab (Cosentyx™) is a fully human monoclonal antibody that targets interleukin-17A, approved for treating psoriasis and psoriatic arthritis in adults who do not respond adequately to other systemic therapies.

It received its first global approval in Japan in December 2014 and was subsequently approved in the USA and EU in early 2015, with ongoing investigations for additional conditions like ankylosing spondylitis and rheumatoid arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Secukinumab: first global approval. Sanford, M., McKeage, K.[2019]

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]

Secukinumab, a monoclonal antibody targeting interleukin-17A, has been shown to significantly improve symptoms and quality of life in patients with active ankylosing spondylitis after 16 weeks of treatment, with benefits maintained for up to 2 years.

The drug is well tolerated and effective in both patients who have never used TNF inhibitors and those who have not responded to or cannot tolerate them, making it a promising treatment option for a diverse group of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Secukinumab: A Review in Ankylosing Spondylitis. Blair, HA., Dhillon, S.[2019]

Citations

1. novartis.com novartis.com/news/media-releases/novartis-cosentyx-meets-primary-and-all-secondary-endpoints-phase-iii-trial-patients-polymyalgia-rheumatica-pmr

Novartis Cosentyx® meets primary and all secondary ... Cosentyx® (secukinumab) achieved statistically significant and clinically meaningful sustained remission vs placebo at Week 521

2. rheumatologyadvisor.com rheumatologyadvisor.com/news/secukinumab-looks-promising-for-polymyalgia-rheumatica/

Secukinumab Looks Promising for Polymyalgia Rheumatica Findings showed the study met the primary endpoint, demonstrating statistically significant and clinically meaningful sustained remission at ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05767034

NCT05767034 | Phase III Study of Efficacy and Safety ... The purpose of this study is to demonstrate the efficacy and safety of secukinumab 300 milligram (mg) and 150 mg administered subcutaneously (s.c.) for 52 ...

4. pmlive.com pmlive.com/pharma_news/novartis-reports-positive-phase-3-results-for-cosentyx-in-polymyalgia-rheumatica/

Novartis reports positive phase 3 results for Cosentyx in ... The REPLENISH trial met all primary and secondary endpoints, demonstrating sustained remission vs placebo.

5. 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 ...

6. rheumnow.com rheumnow.com/news/replenish-secukinumab-works-polymyalgia-rheumatica

Secukinumab Works in Polymyalgia Rheumatica Topline results showed that SEC achieved statistically significant and clinically meaningful sustained remission (primary endpoint) and all ...