Secukinumab for Polymyalgia Rheumatica

(REPLENISH-EXT Trial)

Recruiting at 135 trial locations

Overseen By Andrew Sulich

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Must not be taking: Prohibited medications

Disqualifiers: Chronic infections, Malignancy, Live vaccinations, 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

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

Compensation: Varies

Number of Visits: 15

300 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the long-term safety and tolerability of secukinumab, an immunosuppressant drug, for individuals with polymyalgia rheumatica, a condition causing muscle pain and stiffness. Participants will receive a dose of secukinumab every four weeks for up to two years. The trial seeks individuals who completed a previous secukinumab study, experienced a relapse, and have not required emergency medication since. Participants must not have certain infections or a recent cancer history. 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.

Will I have to stop taking my current medications?

The trial information mentions the use of prohibited medications, but it does not specify which ones. It's best to discuss your current medications with the trial team to see if any need to be stopped.

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

Research has shown that secukinumab is generally safe for patients. Studies found no new safety issues for those using secukinumab. In another study on a similar condition, more patients stayed in remission with secukinumab than with a placebo, and no major safety problems occurred. These results suggest that secukinumab is safe for long-term use, though side effects can still occur. Patients should always discuss any concerns with their doctor. ^{1 2 3 4 5}

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

Most treatments for polymyalgia rheumatica involve corticosteroids, like prednisone, which reduce inflammation but can have significant side effects with long-term use. Secukinumab is unique because it targets a specific protein called interleukin-17A, which plays a role in inflammation. This targeted approach could potentially offer effective relief with fewer side effects compared to broad-acting steroids. Researchers are excited about secukinumab because it might provide a more tailored treatment option, reducing inflammation more precisely and improving patients' quality of life over the long term.

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

Research has shown that secukinumab may help treat polymyalgia rheumatica, a condition causing muscle pain and stiffness. In this trial, all eligible participants will receive secukinumab, starting at 300 mg under the skin every 4 weeks, with possible adjustments to 150 mg if the investigator deems it appropriate. Studies found that more patients experienced lasting relief with secukinumab compared to a placebo, meaning they felt better for a longer time. These results suggest that secukinumab could be a promising option for people with polymyalgia rheumatica. ^{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?

This trial is for patients with Polymyalgia Rheumatica who completed a previous 52-week secukinumab study and had a relapse. They haven't received rescue treatment, and the doctor believes more benefits than risks are present.

Inclusion Criteria

My condition worsened during the follow-up period after my initial treatment.

I completed a 52-week secukinumab study for PMR.

My doctor thinks secukinumab could help me more than harm.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

up to 4 weeks

Treatment Period 1

Participants receive secukinumab from Baseline to Week 24 with visits every 4 weeks

24 weeks

6 visits (in-person), optional visits at Weeks 16 and 20

Treatment Period 2

Participants continue receiving secukinumab up to 2 years with visits every 12 weeks

up to 2 years

8 visits (in-person) every 12 weeks, with option for more frequent visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

16 weeks

1 visit (in-person) 20 weeks after last dose

What Are the Treatments Tested in This Trial?

Interventions

• Secukinumab

Trial Overview The trial tests the long-term safety of Secukinumab in treating Polymyalgia Rheumatica. It's an open-label extension study, meaning everyone knows they're getting Secukinumab and it's given over an extended period.

How Is the Trial Designed?

Group I: Secukinumab 300mg Experimental Treatment 1 Intervention

All eligible participants will receive secukinumab 300 mg s.c. (2 x 150mg/1mL PFS secukinumab) from baseline and every 4 weeks up to 2 years. The study medication may be modified/adjusted after the initial doses of 300mg s.c. (decreased to 150mg s.c. q4w or increased again from 150mg s.c. q4w to 300mg s.c. q4w) if deemed appropriate by the investigator. Dose modification/adjustment may only occur from Week 24 visit onwards. The modification/adjustment of the study medication will be determined at a site visit.

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 (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]

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, 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]

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 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]

Secukinumab, a biologic treatment approved for psoriatic arthritis (PsA) in 2016, shows promising safety and efficacy based on clinical trial evidence, indicating it may be as effective as other treatment options.

Further direct comparison studies are needed to better understand secukinumab's role in treatment guidelines for PsA, as current evidence suggests it is a viable option among existing therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review of the Use of Secukinumab for Psoriatic Arthritis. Patel, NU., Vera, NC., Shealy, ER., et al.[2021]

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]

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

Safety and efficacy of secukinumab in patients with giant ... Secukinumab was tolerated well with no new safety concerns. This proof-of-concept phase 2 study further supports the development of secukinumab as a treatment ...