Anti-Interleukin-6 (IL6) in Calciphylaxis
Tocilizumab for Chronic Kidney Disease (CKD)-Associated Calciphylaxis
Calciphylaxis is a rare but incredibly dangerous condition that causes small blood vessels in the skin to become blocked by calcium buildup and blood clots. This leads to painful skin sores (necrosis) that do not heal easily. Because these open wounds are prone to severe infections, the outlook for patients is often grim; more than half of those diagnosed do not survive past the first year. Currently, there are no Food and Drug Administration (FDA) approved medications specifically designed to stop the progression of this disease. However, recent research has identified a specific culprit: Interleukin-6 (IL-6). The research team is looking at a drug called Tocilizumab to turn off the progression of the disease.
This project aims to investigate whether Tocilizumab can consistently stop the cycle of inflammation and clotting, providing a much-needed lifeline for patients facing this life-threatening diagnosis. Ten participants with calciphylaxis and end-stage kidney disease will be enrolled to receive 3 infusions of Tocilizumab, follow-ups on a weekly basis, during their trip to the dialysis unit, for a total of 16 weeks.
Panoramica dello studio
Stato
Stato
Condizioni
Condizioni
Intervento / Trattamento
Intervento / Trattamento
Tipo di studio
Tipo di studio
Iscrizione (Stimato)
Iscrizione
Fase
Fase
- Fase 1
Contatti e Sedi
Contatto studio
Contatto studio
- Nome: Vipul Chitalia, MD PhD
- Numero di telefono: 617-638-7343
- Email: vichitali@bu.edu
Backup dei contatti dello studio
- Nome: Saran Lotfollahzadeh, PhD
- Email: slotfoll@bu.edu
Luoghi di studio
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Massachusetts
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Boston, Massachusetts, Stati Uniti, 02118
- Boston Medical Center
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Criteri di partecipazione
Criteri di ammissibilità
Criteri di ammissibilità
Età idonea allo studio
- Adulto
- Adulto più anziano
Accetta volontari sani
Descrizione
Inclusion Criteria:
- Must have a clinical diagnosis of calciphylaxis (calcific uremic arteriolopathy) as determined by a board-certified dermatologist or surgeon.
Diagnosis must be supported by either:
- Histopathology: A skin biopsy showing characteristic medial arteriolar calcification, subintimal fibrosis, or microvascular thrombosis.
- Clinical Presentation: In cases where a biopsy is clinically contraindicated, the presence of characteristic ischemic or necrotic skin lesions in a distribution typical for calciphylaxis (e.g., adipose-rich areas like the abdomen, thighs, or buttocks).
Must have advanced kidney disease, defined as:
- End-Stage Kidney Disease (ESKD): Requiring maintenance hemodialysis or peritoneal dialysis.
- Chronic Kidney Disease (CKD): Stage 4 or 5 [estimated Glomerular Filtration Rate (eGFR) < 30 mL/min/1.73m²].
- Participants must be able to understand and provide written informed consent. in accordance with local institutional and regulatory guidelines.
- Subjects of childbearing potential must agree to use highly effective contraception for the duration of the study and for at least 3 months following the final dose of Tocilizumab.
- Must be willing to undergo blood draws for systemic biomarker analysis (CRP, sTF) as outlined in the study schedule, and safety monitoring.
Exclusion Criteria:
- Presence of any active, clinically significant infection (bacterial, viral, fungal, or opportunistic) that, in the opinion of the investigator, would pose an unacceptable risk to the patient during IL-6 inhibition.
- Known history of diverticulitis, intestinal perforation, or active gastrointestinal ulceration, due to the increased risk of GI perforation associated with tocilizumab.
- Evidence of active tuberculosis (TB) or untreated latent TB [confirmed via positive Interferon-Gamma Release Assay (IGRA) or purified protein derivative (PPD) skin test].
- Evidence of active Hepatitis B [HBsAg positive, or HBcAb positive with detectable hepatitis B virus (HBV) DNA) or active Hepatitis C (HCV RNA positive]
Absolute Neutrophil Count (ANC) < 1,500 cells/mm³.
- Platelet count < 100,000 cells/mm³.
- Hemoglobin < 8.0 g/dL.
- Baseline elevations of (alanine aminotransferase test (ALT) or aspartate aminotransferase test (AST) > 1.5 times the upper limit of normal (ULN).
- Known active malignancy or a history of malignancy within the last 5 years (excluding successfully treated non-melanoma skin cancer or carcinoma in situ of the cervix).
- History of multiple sclerosis or other central demyelinating disorders.
- Recent or planned use of other biological response modifiers (e.g., tumor necrosis factor (TNF)-alpha inhibitors, IL-1 receptor antagonists, or B-cell depleting agents) within 3 months prior to enrollment.
- Receipt of a live or attenuated vaccine within 4 weeks prior to the first dose, or planned vaccination during the study period and for 4 weeks following the final dose.
- Known hypersensitivity to tocilizumab or any of its excipients.
- Pregnant or breastfeeding women, or those planning to become pregnant during the study period.
- Individuals who are unable to provide personal informed consent and do not have a Legally Authorized Representative (LAR) available to provide consent on their behalf
- Any other concurrent medical or psychiatric condition that, in the investigator's judgment, would make the subject inappropriate for the study or interfere with safety evaluations.
- Prisoners
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: N / A
- Modello interventistico: Assegnazione di gruppo singolo
- Mascheramento: Nessuno (etichetta aperta)
Numero di armi
Armi e interventi
Gruppo di partecipanti / ArmGruppo di partecipanti / Arm |
Intervento / TrattamentoIntervento / Trattamento |
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Sperimentale: Tocilizumab group
Participants will receive a total of 3 doses of intravenous tocilizumab.
One does will be administered every 4 weeks.
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Tocilizumab (8 mg/kg) will be administered intravenously every 4 weeks with weekly monitoring during the participant's dialysis visit.
Final assessments and safety labs will be performed 4 weeks after the last dose.
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability
Lasso di tempo: weekly for 18 weeks
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Safety will be measured through the incidence and severity of Treatment-Emergent Adverse Events (TEAEs), graded according to the CTCAE v5.0, with focused vigilance on serious infections, gastrointestinal complications, and infusion-related hypersensitivity.
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weekly for 18 weeks
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Feasibility of treatment
Lasso di tempo: 18 weeks
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Feasibility will be evaluated through specific operational metrics, including the ratio of successfully enrolled participants to those screened and the percentage of participants who complete the full 18-week study procedure schedule.
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18 weeks
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Misure di risultato secondarie
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Measurement of wound regression
Lasso di tempo: weekly for 18 weeks
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Quantitative measurement of the surface area (length x width) of the primary calciphylaxis lesion(s) using digital photography and standardized planimetry software will be done to track quantitative changes in ulcer surface area indicator of reduced ischemic necrosis.
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weekly for 18 weeks
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Pain assessment
Lasso di tempo: weekly for 18 weeks
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Patient-reported Visual Analog Scale (VAS) scores for pain intensity.
These intensity ratings will be cross-referenced with weekly Morphine Milligram Equivalent (MME) calculations and daily pain logbook entries to determine whether the intervention successfully reduces the overall systemic opioid burden.
Higher VAS scores are associated with greater pain intensity.
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weekly for 18 weeks
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Collaboratori e investigatori
Sponsor
Sponsor
Investigatori
Investigatori
- Investigatore principale: Vipul Chitalia, MD PhD, Boston Medical Center
Studiare le date dei record
Studia le date principali
Inizio studio (Stimato)
Inizio studio
Completamento primario (Stimato)
Completamento primario
Completamento dello studio (Stimato)
Completamento dello studio
Date di iscrizione allo studio
Primo inviato
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Effettivo)
Primo Inserito
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento pubblicato
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Malattie urogenitali
- Processi patologici
- Malattie urogenitali maschili
- Malattie renali
- Malattie urologiche
- Malattie urogenitali femminili
- Malattie urogenitali femminili e complicanze della gravidanza
- Malattia cronica
- Attributi della malattia
- Malattie metaboliche
- Insufficienza renale
- Disturbi del metabolismo del calcio
- Calcinosi
- Condizioni patologiche, segni e sintomi
- Malattie nutrizionali e metaboliche
- Insufficienza renale cronica
- Insufficienza renale cronica
- Calcifilassi
- tocicizumab
Altri numeri di identificazione dello studio
Altri numeri di identificazione dello studio
- H-46722
Piano per i dati dei singoli partecipanti (IPD)
Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?
Informazioni su farmaci e dispositivi, documenti di studio
Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti
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prodotto fabbricato ed esportato dagli Stati Uniti
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