- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT07708038
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.
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Type d'étude
Inscription (Estimé)
Phase
- La phase 1
Contacts et emplacements
Coordonnées de l'étude
- Nom: Vipul Chitalia, MD PhD
- Numéro de téléphone: 617-638-7343
- E-mail: vichitali@bu.edu
Sauvegarde des contacts de l'étude
- Nom: Saran Lotfollahzadeh, PhD
- E-mail: slotfoll@bu.edu
Lieux d'étude
-
-
Massachusetts
-
Boston, Massachusetts, États-Unis, 02118
- Boston Medical Center
-
-
Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
- Adulte
- Adulte plus âgé
Accepte les volontaires sains
La description
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
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: N / A
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: Tocilizumab group
Participants will receive a total of 3 doses of intravenous tocilizumab.
One does will be administered every 4 weeks.
|
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.
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability
Délai: weekly for 18 weeks
|
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.
|
weekly for 18 weeks
|
|
Feasibility of treatment
Délai: 18 weeks
|
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.
|
18 weeks
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Measurement of wound regression
Délai: weekly for 18 weeks
|
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.
|
weekly for 18 weeks
|
|
Pain assessment
Délai: weekly for 18 weeks
|
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.
|
weekly for 18 weeks
|
Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Chercheur principal: Vipul Chitalia, MD PhD, Boston Medical Center
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Estimé)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Maladies urogénitales
- Processus pathologiques
- Maladies urogénitales masculines
- Maladies rénales
- Maladies urologiques
- Maladies urogénitales féminines
- Maladies urogénitales féminines et complications de la grossesse
- Maladie chronique
- Attributs de la maladie
- Maladies métaboliques
- Insuffisance rénale
- Troubles du métabolisme calcique
- Calcinose
- Conditions pathologiques, signes et symptômes
- Maladies nutritionnelles et métaboliques
- Insuffisance rénale chronique
- Insuffisance rénale chronique
- Calciphylaxie
- toilizumab
Autres numéros d'identification d'étude
- H-46722
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
Informations sur les médicaments et les dispositifs, documents d'étude
Étudie un produit pharmaceutique réglementé par la FDA américaine
Étudie un produit d'appareil réglementé par la FDA américaine
produit fabriqué et exporté des États-Unis.
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .