Treatment of Refractory Hemochromatosis Rheumatism by Anakinra: a Preliminary Phase II Study
Information source: Rennes University Hospital
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Refractory Hemochromatosis Rheumatism
Intervention: Anakinra (Drug)
Phase: Phase 2
Status: Recruiting
Sponsored by: Rennes University Hospital Official(s) and/or principal investigator(s): Pascal Richette, Principal Investigator, Affiliation: Groupe Hospitalier Lariboisière - Paris Pascal Guggenbuhl, Principal Investigator, Affiliation: Rennes University Hospital
Overall contact: Pascal Guggenbuhl, Phone: +33 2 99 26 71 40, Email: pascal.guggenbuhl@chu-rennes.fr
Summary
Treatment of refractory hemochromatosis rheumatism by Anakinra. Prospective, multicenter,
non-randomised, single-arm, open-label, phase II trial.
Clinical Details
Official title: Treatment of Refractory Hemochromatosis Rheumatism by Anakinra: a Preliminary Phase II Study
Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Rate of patients with improvement of joint pain
Secondary outcome: Assessment of the disease activityAssessment of the number of painful joints Assessment of the number of swollen joints Assessment of analgesics consumption Assessment of non-steroidal anti-inflammatory drugs (NSAID) consumption Assessment of colchicine consumption Assessment of steroids injections consumption Assessment of the quality of life Assessment of the quality of life Functional evaluation Functional evaluation Assessment of joint damage Synovial fluid analysis Synovial fluid analysis Synovial fluid analysis Biological effects on inflammation and iron metabolism Time at which Cmax of anakinra was observed (Tmax) Maximum observed concentration (Cmax) of anakinra Half-life (T1/2) of anakinra Area under the concentration-time curve of time 0 to the last detectable concentration (AUC0−last) of anakinra Area under the concentration-time curve of time 0 to infinity (AUC0−∞) of anakinra Plasma clearance after administration (CL/F) of anakinra
Detailed description:
Hereditary hemochromatosis (HH) is a genetic disease characterized by tissue iron overload.
The most common genotype is homozygosity for the p. Cys282Tyr mutation of the HFE gene (MIM
235200). It is a serious disease which can lead to life threatening complications such as
cirrhosis, liver carcinoma, heart failure or diabetes mellitus. Currently, these
complications can be prevented by phlebotomies. Two-thirds of patients complain of joint
symptoms which represent a major cause of impaired quality of life. Phlebotomies are
ineffective on HH rheumatism and patients' quality of life is very often altered while life
threatening complications are prevented. Furthermore, there is a significant higher risk for
joint replacement surgery in these patients compared to controls (X 9). There is currently
no approved treatment for hemochromatosis rheumatism. As it looks like severe
osteoarthritis, calcium pyrophosphate deposition disease (CPDD) or chondrocalcinosis,
symptomatic treatments are employed such as analgesics (type I or II), non-steroidal
anti-inflammatory drugs or colchicine in case of acute joint flare, corticosteroids
intra-articular injections or occasionally oral glucocorticoids. However in some cases these
treatments remain ineffective leading to a true disability.
Frequently, there are local inflammatory symptoms. Interleukin 1ß (IL1ß) plays a key role in
the pathogenesis of crystal arthropathies (CPDD or gout).
Anakinra (IL-1Ra), a drug approved in France for rheumatoid arthritis, has been tested in
short series or case controls in refractory gout, CPDD and only in two patients with HH
rheumatism. The aim of this phase II study is to test the efficacy of anakinra in patients
with hemochromatosis and refractory joint pain. It is also to evaluate the opportunity to
perform a phase III trial. In the absence of available data on the evolution of this
rheumatism treated by anakinra in this population of patients resistant to standard therapy,
the investigators consider that a phase III trial would not be justifiable if the rate of
success is insufficient.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Patients with age equal to or over 18 years old,
- Patients with proved hereditary hemochromatosis with homozygosity for the C282Y
mutation of the HFE gene,
- Patients with rheumatism related to hemochromatosis, considered by the rheumatologist
refractory to usual treatment defined by a persistent painful symptomatology despite
a treatment of at least one month with level 2 analgesics (weak opioids) at maximal
dose, NSAID, colchicine, steroid injection or a combination of these treatments,
- Patients with pain > 40/100mm measured by VAS (pain of the last 48 hours),
- Effective contraception to be used during treatment and until 48h after the last
administration for women of reproductive age,
- Patients who have given written informed consent.
Exclusion Criteria:
- Other cause of inflammatory rheumatisms such as Rheumatoid Arthritis,
Spondyloarthropathies, psoriatic arthritis, or systemic diseases,
- Ongoing treatment with Methotrexate, Hydroxychloroquine, biologic or
immunosuppressive drugs
- Malignant pathology, monoclonal gammopathy,
- Intolerance to anakinra,
- Contraindications to the use of anakinra: pregnancy or breastfeeding,
hypersensitivity to any of the excipients or to proteins from E. coli, severe renal
impairment (creatinine clearance <30 ml / minute), neutropenia (neutrophil count <1. 5
x 109 / l), ongoing infection
- Patients that cannot follow the protocol,
- Persons subject to major legal protection (safeguarding justice, guardianship,
trusteeship), persons deprived of liberty.
Locations and Contacts
Pascal Guggenbuhl, Phone: +33 2 99 26 71 40, Email: pascal.guggenbuhl@chu-rennes.fr
Groupe Hospitalier Lariboisière, Paris, France; Not yet recruiting Pascal Richette, Phone: +33 1 49 95 62 98, Email: pascal.richette@lrb.aphp.fr
Rennes University Hospital, Rennes 35033, France; Recruiting Pascal Guggenbuhl, Phone: +33 2 99 26 71 40, Email: pascal.guggenbuhl@chu-rennes.fr Pascal Guggenbuhl, Principal Investigator
Additional Information
Starting date: February 2015
Last updated: August 20, 2015
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