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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


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 activity

Assessment 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.


Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.


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

Page last updated: August 23, 2015

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