Pragmatic, Open-Label Study to Pilot Evaluation for Clinical Trials in Relapsing Polychondritis (PROSECT RP)

Pragmatic, Open-Label, Two-Stage, Pilot Study of Effectiveness of Immunomodulatory Medications for Patients With Relapsing Polychondritis

Open label pragmatic two-stage non-randomized trial comparing the effectiveness of five different standard of care treatment options for patients with relapsing polychondritis (RP).

Study Overview

• Status: Recruiting
• Conditions: Relapsing Polychondritis
• Intervention / Treatment: Drug: Methotrexate (MTX); Drug: Azathioprine (AZA); Biological: Adalimumab; Biological: Infliximab; Biological: Tocilizumab

Detailed Description

Twenty eligible patients with mild to moderately active RP within 60 days prior to screening will be enrolled to the study.

Subjects will be eligible to enroll into stage 1 if they are naïve to methotrexate (MTX) or azathioprine (AZA), or having active disease on MTX or AZA for 8 weeks or less. Patients naïve to MTX and AZA will be started on MTX. AZA will be started if there is a contraindication to MTX. Patients on MTX/AZA for 8 weeks or less with active disease will be continued with the respective medication.

Patients who do not meet primary effectiveness end point in Stage 1 or develop relapse of RP or intolerance to MTX/AZA will move to Stage 2.

Patients eligible to be enrolled to Stage 2 directly

1. History of intolerance or side effects to MTX or AZA with active disease
2. Currently on MTX or AZA for at least 8 weeks or has received it within the past 60 days for at least 8 weeks and still has mild/ moderate active disease

All patients in Stage 2 will be started on Tumor necrosis factor inhibitor (TNFi) or Interleukin 6 inhibitor (IL6i). The two TNFis that will be used in the trial are adalimumab or infliximab. The choice between the 2 TNFis will be based on patients' preference/ feasibility. The IL6i in the study will be tocilizumab.

All patients will receive glucocorticoids (GC) which will be tapered to 5 mg daily by week 21 according to a standardized schedule in both stages of the trial.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Carol McAlear; Phone Number: 781-321-4567; Email: cmcalear@upenn.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania
      • Contact: Jessica Nguyen; Email: Jessica.Nguyen2@PennMedicine.upenn.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

A. ≥18 years of age

B. Must fulfill McAdam's or Damiani's or Michet's Criteria Diagnostic Criteria for Relapsing Polychondritis McAdam's Criteria (1976)

≥ 3 criteria out of 6 of the following:

1. Bilateral auricular chondritis
2. Non-erosive seronegative polyarthritis
3. Nasal chondritis
4. Ocular inflammation
5. Respiratory tract chondritis
6. Cochlear and/or vestibular dysfunction

Damiani's Criteria (1979)

1. ≥3 of McAdam's Criteria as above
2. ≥1 of McAdam's Criteria with histological confirmation of chondritis
3. ≥2 of McAdam's Criteria with positive response to glucocorticoids or dapsone

Michet's Criteria (1986)

Presence of ≥2 of the following criteria:

1. Auricular chondritis
2. Nasal chondritis
3. Laryngotracheal chondritis

Or presence of ≥1 of the above criteria and ≥2 of the following criteria

1. Seronegative inflammatory arthritis
2. Ocular inflammation
3. Hearing loss
4. Vestibular dysfunction

C. Mild to moderately active disease within 60 days prior to screening where the symptoms cannot be attributed to any cause other than RP and which, in the investigator's opinion, requires addition/ increase in prednisone dose between 15-60 mg/ day.

At the time of enrollment and during the trial, the following symptoms of active disease which will be evaluated:

1. Auricular inflammation: defined as increase/ new onset pain/ swelling/redness of external ear(s), ear canal
2. Nasal inflammation: defined as increase/ new onset pain/ swelling/redness of external nose
3. Ocular inflammation: defined as new onset/ worsening unilateral/ bilateral episcleritis/scleritis/ uveitis.
4. Inflammatory arthritis: defined as new onset/ worsening morning stiffness≥30 minutes, physician diagnosed tenderness/swelling in ≥1 joint; new onset/ worsening costochondritis.
5. Mild to moderate airway inflammation: defined as new onset/ worsening mild to moderate inflammation of upper airway diagnosed by direct laryngoscopy and attributed to RP; abnormal CT airway/ bronchoscopy showing wall thickening of airway (larynx, trachea, bronchi) and absence of severe manifestations such as new onset SGS/tracheomalacia/ bronchomalacia.
6. Sinonasal disease: defined as new onset/ increase in nasal crusting, discharge bleeding
7. Constitutional symptoms: defined as new onset/ worsening fever, unintentional weight loss of ≥ 5% of body weight, night sweats Patients must have at least 1 of the first 5 criteria within the past 60 days prior to the enrollment.

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

E. Both men and women of childbearing potential must be willing to use an effective means of birth control while receiving treatment throughout the study. Effective contraception methods include abstinence, oral contraceptives (birth control pills), intra-uterine-device, diaphragm, approved hormone injections, condoms, or medical sterilization.

F. Willing and able to provide written informed consent.

Exclusion Criteria:

A. Severe disease manifestations within the past 14 days requiring hospitalization, and/or intravenous pulsed dose glucocorticoid treatment for disease control.

B. Prior exposure of 4 weeks or longer to adalimumab, infliximab, and/or tocilizumab.

C. Prior exposure to >2 biologics and/or JAKi.

D. Evidence of active infection.

E. Known infection with human immunodeficiency virus (HIV), untreated hepatitis C infection, or a positive hepatitis B virus surface antigen.

F. Patients at risk for tuberculosis (TB) defined as follows:

1. Current clinical, radiographic or laboratory evidence of active TB, even if currently being treated. Chest x-rays (posterior/anterior and lateral) obtained within the 6 months prior to screening and TB testing (IFN gamma release assay or PPD) performed in the past month prior to screening will be accepted; however, a copy of the reports must be placed in the participant binder.
2. A history of active TB unless there is documentation that the patient had received prior anti-TB treatment that was appropriate in duration and type according to local health authority guidelines.
3. Patients with a positive TB screening test indicative of latent TB will not be eligible for the study unless they: i. Have no evidence of current TB based on chest x-ray performed during the screening period and by history and physical exam, and ii. They are currently being treated for latent TB or the site has documentation of successful prior treatment of latent TB. Treatment regimens should be dictated by local guidelines as long as the treatment dose and duration meet or exceed local health authority guidelines. Patients with latent TB may be eligible for the trial prior to completion of treatment as long as they have completed at least 4 weeks of treatment and they have no evidence of current TB on chest x-ray at screening.

G. Inability to comply with study guidelines.

H. Cytopenia: platelet count <80,000/mm3, absolute neutrophil count <1500/mm3, hematocrit < 20%.

I. Other uncontrolled disease (co-morbidity) that could prevent a subject from fulfilling the study requirements or that would increase the risk of study procedures.

J. Patients who have a present malignancy or previous malignancy within the last 5 years prior to screening (except documented history of cured non-metastatic squamous or basal cell skin carcinoma or cervical carcinoma in situ). Patients who had a screening procedure that is suspicious for malignancy, and in whom the possibility of malignancy cannot be reasonably excluded following additional clinical, laboratory or other diagnostic evaluations.

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

L. A live vaccination < 4 weeks before enrollment

M. Presence of any of the following diseases:

1. ANCA-associated vasculitis
2. Polyarteritis nodosa
3. Giant cell arteritis
4. Takayasu's arteritis
5. Cogan's syndrome
6. Tuberculosis or atypical mycobacterial infections
7. Deep fungal infections
8. Lymphoma, lymphomatoid granulomatosis, or other type of malignancy that mimics vasculitis
9. Overlap with other systemic autoimmune diseases which would impair assessment of response
10. Diagnosis of VEXAS syndrome

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Azathioprine or Methotrexate	Drug: Methotrexate (MTX); Weekly methotrexate dose of 20 mg (oral or subcutaneous).; Drug: Azathioprine (AZA); Azathioprine dose will be 2-3 mg/kg body weight per day.
Experimental: Adalimumab, Infliximab, or Tocilizumab	Biological: Adalimumab; Adalimumab dose will be 40 mg subcutaneously every 1-2 weeks; Biological: Infliximab; Infliximab dose will be 5mg/kg at week 0 and week 2, and then every 4-8 weeks.; Biological: Tocilizumab; Tocilizumab dose will be 162 mg subcutaneous injection every week or 4-8 mg/kg every 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of the study drugs for the treatment of relapsing polychondritis.	The proportion of subjects in remission at week 26	26 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physician's global assessment of response	Health-related quality of life as measured using physician's global assessment scale.	Assessed at weeks 0, 12, and 26
Response rates for each of the study drugs	Proportion of patient with complete response and significant response to therapy at weeks 12 and 26	Response evaluated weeks 12 and 26
Patient's global assessment of response	Health-related quality of life as measured using patient's global assessment scale.	Assessed at weeks 0, 12, and 26
Health-related quality of life	Health-related quality of life as measured using SF-36	Assessed at weeks 0, 12, and 26
Time to disease flare	Disease flare defined as increase on a disease activity instrument by at least 1 point	26 weeks
Safety of study drugs in RP	Safety of study drugs in patients with RP as assessed by reported adverse events.	26 weeks

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Investigators: Principal Investigator: Shubhasree Banerjee, MD, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: April 15, 2025
• First Submitted That Met QC Criteria: April 15, 2025
• First Posted (Actual): April 23, 2025

Study Record Updates

• Last Update Posted (Actual): September 2, 2026
• Last Update Submitted That Met QC Criteria: August 28, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Vasculitis; RP; Relapsing Polychondritis; Polychondritis, relapsing
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Vascular Diseases; Cardiovascular Diseases; Connective Tissue Diseases; Cartilage Diseases; Skin and Connective Tissue Diseases; Polychondritis, Relapsing; Vasculitis; Amino Acids, Peptides, and Proteins; Proteins; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nucleic Acids, Nucleotides, and Nucleosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Purines; Nucleosides; Pterins; Pteridines; Aminopterin; Thionucleosides; Mercaptopurine; Adalimumab; Infliximab; Methotrexate; Azathioprine; tocilizumab
• Other Study ID Numbers: VCRC5565

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No