Clinical Trial: Treatment of Refractory Hemochromatosis Rheumatism by Anakinra: a Preliminary Phase II Study

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Treatment of Refractory Hemochromatosis Rheumatism by Anakinra: a Preliminary Phase II Study

Brief Summary: Treatment of refractory hemochromatosis rheumatism by Anakinra. Prospective, multicenter, non-randomised, single-arm, open-label, phase II trial.

Detailed Summary:

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
Sponsor: Rennes University Hospital

Current Primary Outcome: Rate of patients with improvement of joint pain [ Time Frame: Day 15 ]

Original Primary Outcome: Rate of patients with improvement of joint pain [ Time Frame: Day 90 ]

Current Secondary Outcome:

• Assessment of the disease activity [ Time Frame: Day 0, day 15, day 30, day 60, day 90 ]
  Assessment of the disease activity by Visual analog scale (VAS)
• Assessment of the number of painful joints [ Time Frame: Day 0, day 15, day 30, day 60, day 90 ]
  Assessment of the number of painful joints by a clinical exam
• Assessment of the number of swollen joints [ Time Frame: Day 0, day 15, day 30, day 60, day 90 ]
  Assessment of the number of swollen joints by a clinical exam
• Assessment of analgesics consumption [ Time Frame: Day 0, day 15, day 30, day 60, day 90 ]
• Assessment of non-steroidal anti-inflammatory drugs (NSAID) consumption [ Time Frame: Day 0, day 15, day 30, day 60, day 90 ]
• Assessment of colchicine consumption [ Time Frame: Day 0, day 15, day 30, day 60, day 90 ]
• Assessment of steroids injections consumption [ Time Frame: Day 0, day 15, day 30, day 60, day 90 ]
• Assessment of the quality of life [ Time Frame: Day 0, day 15, day 30, day 90 ]
  Assessment of the quality of life by the SF36 questionnaire
• Assessment of the quality of life [ Time Frame: Day 0, day 15, day 30, day 90 ]
  Assessment of the quality of life by the HAQ questionnaire
• Functional evaluation [ Time Frame: Day 0, day 15, day 30, day 90 ]
  Functional evaluation by WOMAC index for hip and knee
• Functional evaluation [ Time Frame: Day 0, day 15, day 30, day 90 ]
  Functional evaluation by Dreiser index for hands
• Assessment of joint damage [ Time Frame: Day 0, day 90 ]
  Assessment of joint damage by X-rays and Doppler ultrasound
• Synovial fluid analysis [ Time Frame: 3 months ]
  Puncture if acute joint effusion : cells count
• Synovial fluid analysis [ Time Frame: 3 months ]
  Puncture if acute joint effusion : search for crystals presence
• Synovial fluid analysis [ Time Frame: 3 months ]
  Puncture if acute joint effusion : iron parameters markers
• Biological effects on inflammation and iron metabolism [ Time Frame: Day 0, day 15, day 30, day 60, day 90 ]
  Biological/Vaccine : iron and inflammatory markers
• Time at which Cmax of anakinra was observed (Tmax) [ Time Frame: Predose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 15, 18, 21, 24 hours post-dose ]
  Pharmacokinetics study
• Maximum observed concentration (Cmax) of anakinra [ Time Frame: Predose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 15, 18, 21, 24 hours post-dose ]
  Pharmacokinetics study
• Half-life (T1/2) of anakinra [ Time Frame: Predose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 15, 18, 21, 24 hours post-dose ]
  Pharmacokinetics study
• Area under the concentration-time curve of time 0 to the last detectable concentration (AUC0−last) of anakinra [ Time Frame: Predose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 15, 18, 21, 24 hours post-dose ]
  Pharmacokinetics study
• Area under the concentration-time curve of time 0 to infinity (AUC0−∞) of anakinra [ Time Frame: Predose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 15, 18, 21, 24 hours post-dose ]
  Pharmacokinetics study
• Plasma clearance after administration (CL/F) of anakinra [ Time Frame: Predose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 15, 18, 21, 24 hours post-dose ]
  Pharmacokinetics study

Original Secondary Outcome: Same as current

Information By: Rennes University Hospital

Dates:
Date Received: September 23, 2014
Date Started: February 4, 2015
Date Completion: January 2018
Last Updated: February 14, 2017
Last Verified: February 2017