Immunomodulatory Medications for Polychondritis

(PROSECT RP Trial)

Overseen By Carol McAlear

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Pennsylvania

Must not be taking: Biologic DMARDs

Disqualifiers: Severe disease, CNS disease, Cardiac disease, Active infection, Malignancy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of different standard treatments for relapsing polychondritis (RP), a condition characterized by inflamed cartilage. Participants will receive one of five medications: Adalimumab, Azathioprine, Infliximab, Methotrexate, or Tocilizumab. The trial seeks individuals who have experienced RP symptoms, such as ear or nose pain, joint swelling, or breathing issues, within the last 60 days. By testing these treatments, the researchers aim to improve care for those managing this chronic condition. As a Phase 2 trial, it focuses on assessing treatment efficacy in an initial, smaller group, offering participants an opportunity to contribute to advancing RP care.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, patients with current or prior use of certain medications like methotrexate or azathioprine are eligible, while those with exposure to biologic DMARDs are excluded. It's best to discuss your specific medications with the trial team.

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

A previous study showed that treatment with infliximab and tocilizumab led to significant improvements in patients over six months, suggesting these drugs are generally well-tolerated. Another study found that 62.9% of patients responded positively to biologics like adalimumab, infliximab, and tocilizumab, indicating they are fairly safe.

For azathioprine and methotrexate, the information is less clear. However, one report noted a case of pancreatitis (inflammation of the pancreas) in a patient using azathioprine, suggesting some risk of side effects. Therefore, monitoring is important.

Overall, while these treatments have shown promise, patients should pay attention to how their bodies respond and discuss any concerns with their doctors. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for polychondritis because they offer new ways to tackle this condition. Unlike standard therapies that often rely on corticosteroids to manage inflammation, these investigational treatments include biologics like Adalimumab, Infliximab, and Tocilizumab, which specifically target inflammatory cytokines such as TNF-alpha and IL-6, potentially reducing inflammation more effectively. Additionally, Adalimumab and Infliximab are administered via injection, which can provide targeted and sustained relief compared to oral medications. These unique approaches could offer more precise control over the symptoms of polychondritis, providing hope for better disease management.

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

This trial will evaluate the effectiveness of different immunomodulatory medications for relapsing polychondritis (RP). Participants in one arm of the trial will receive Adalimumab, Infliximab, or Tocilizumab. Studies have shown that these treatments can be effective for RP, with Infliximab and Tocilizumab improving symptoms in patients with certain inflammatory conditions. Specifically, a series of cases demonstrated that Adalimumab provided partial or complete relief in about 86% of cases, helping many patients with symptoms like breathing difficulties.

In another arm of the trial, participants will receive Azathioprine or Methotrexate. Reviews of studies report a response rate of around 72% for these treatments, which is promising. Both drugs are commonly used to manage the symptoms of this challenging condition. ^{1 2 6 7 8}

Who Is on the Research Team?

Shubhasree Banerjee, MD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

This trial is for patients with relapsing polychondritis, a condition where cartilage becomes inflamed. Participants should have this diagnosis and be in need of treatment.

Inclusion Criteria

Willing and able to provide written informed consent

Must fulfill McAdam's or Damiani's or Michet's Criteria Diagnostic Criteria for Relapsing Polychondritis

Willing and able to comply with treatment and follow-up procedures

Exclusion Criteria

Patients at risk for tuberculosis (TB)

Inability to comply with study guidelines

Receipt of an investigational agent or device within 30 days prior to enrollment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Stage 1 Treatment

Participants receive methotrexate (MTX) or azathioprine (AZA) for up to 8 weeks if naïve or with active disease on these medications

8 weeks

Stage 2 Treatment

Participants who do not meet primary effectiveness end point in Stage 1 or develop relapse/intolerance to MTX/AZA will receive TNFi or IL6i

18 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Adalimumab
• Azathioprine
• Infliximab
• Methotrexate
• Tocilizumab

Trial Overview The study tests five medications: Methotrexate (MTX), Azathioprine (AZA), Adalimumab, Tocilizumab, and Infliximab to see which is most effective for treating relapsing polychondritis. It's an open-label, non-randomized pilot study.

How Is the Trial Designed?

Group I: Azathioprine or Methotrexate Experimental Treatment 2 Interventions

Group II: Adalimumab, Infliximab, or Tocilizumab Experimental Treatment 3 Interventions

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10366079/

Six-month outcomes of infliximab and tocilizumab therapy ... IFX and TCZ infusions showed statistically significant improvement of non-infectious RV as shown by ASUWOG FA Scoring System.

2. clinexprheumatol.org clinexprheumatol.org/article.asp?a=7121

Biologics in relapsing polychondritis: a case series A TNF-antagonist was most frequently used as first-line biologic therapy (7/9), leading to partial or complete efficacy in six cases (85.7%). Loss of efficacy ...

3. acrabstracts.org acrabstracts.org/abstract/biologic-therapy-for-relapsing-polychondritis-old-and-new-efficacy-indices/

Biologic Therapy For Relapsing Polychondritis: Old and ... At 12 months, anti-TNF were effective in 67% (etanercept in 60%) and anakinra in 50% (no follow-up at 12 months is yet available for tocilizumab), RPDAI and ESR ...

4. acrjournals.onlinelibrary.wiley.com acrjournals.onlinelibrary.wiley.com/doi/10.1002/acr2.70027

Clinical Manifestations and Treatment in Patients With ... Relapsing polychondritis (RP) is a rare, heterogeneous, multisystem disease lacking standard treatment guidelines. This study describes clinical manifestations.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6946571/

Assessment of TNF-α inhibitors in airway involvement of ... Anti-TNF-α therapy was associated with improved health status and respiratory symptoms in 67.8% and 60.1% of cases, respectively.

6. rheumatologyadvisor.com rheumatologyadvisor.com/news/efficacy-safety-of-biologics-assessed-in-relapsing-polychondritis/

Efficacy, Safety of Biologics Assessed in Relapsing ... Response rates and complete response rates during the first 6 months were 62.9% and 19.0%, respectively. Response rates were the lowest for ...

7. acrabstracts.org acrabstracts.org/abstract/efficacy-and-safety-of-biologics-in-relapsing-polychondritis-a-national-multicenter-study-in-france/

Efficacy and Safety of Biologics in Relapsing Polychondritis Outcomes are presented in Table 1. PR or CR rate during the first 6 months was 62.9% while CR rate was 19.0%. There was only a modest reduction ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12090363/

Clinical Manifestations and Treatment in Patients With ... This is a cross‐sectional study and does not report follow‐up or outcome data. There are plans to analyze the clinical data and outcomes when a ...