Secukinumab for Polymyalgia Rheumatica

(REPLENISH Trial)

Recruiting at 146 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

381 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests secukinumab injections for adults with relapsed Polymyalgia Rheumatica (PMR). The treatment aims to reduce inflammation by calming the immune system. Researchers will compare the effectiveness and safety of secukinumab over a period of time. Secukinumab has been shown to improve signs and symptoms in various inflammatory conditions such as ankylosing spondylitis and psoriatic arthritis in multiple clinical trials.

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.

What data supports the effectiveness of the drug Secukinumab for treating Polymyalgia Rheumatica?

Secukinumab has been shown to be effective in treating other inflammatory conditions like psoriatic arthritis and ankylosing spondylitis by targeting a protein called interleukin-17A, which plays a role in inflammation. This suggests it might also help with Polymyalgia Rheumatica, which involves inflammation. ^{1 2 3 4 5}

Is secukinumab generally safe for human use?

Secukinumab, also known as Cosentyx, has been studied for conditions like rheumatoid arthritis and psoriatic arthritis. It is generally well tolerated, with common side effects being mild to moderate infections, such as colds. It has been approved for use in several countries, indicating a favorable safety profile. ^{1 2 4 6 7}

How does the drug Secukinumab differ from other treatments for polymyalgia rheumatica?

Secukinumab is unique because it is a monoclonal antibody that targets interleukin-17A, a protein involved in inflammation, and is administered subcutaneously (under the skin). This mechanism of action is different from traditional treatments for inflammatory conditions, which often involve corticosteroids or non-steroidal anti-inflammatory drugs (NSAIDs). ^{1 2 4 5 8}

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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 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 (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, 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]

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]

References

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

Secukinumab: A Review in Psoriatic Arthritis. [2019]

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

Secukinumab: A Review in Psoriatic Arthritis. [2021]

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

Secukinumab for rheumatology: development and its potential place in therapy. [2019]

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

Secukinumab: first global approval. [2019]

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

Secukinumab: A Review in Ankylosing Spondylitis. [2019]

6. Germany 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. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Secukinumab after anti-tumour necrosis factor-α therapy: a phase III study in active rheumatoid arthritis. [2019]

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

Secukinumab for the treatment of psoriatic arthritis. [2019]