Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Treatment of Refractory Hemochromatosis Rheumatism by Anakinra: a Preliminary Phase II Study (THERA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02263638
Recruitment Status : Terminated (Poor recruitment)
First Posted : October 13, 2014
Last Update Posted : March 12, 2019
Sponsor:
Information provided by (Responsible Party):
Rennes University Hospital

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

Condition or disease Intervention/treatment Phase
Refractory Hemochromatosis Rheumatism Drug: Anakinra Phase 2

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 17 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Treatment of Refractory Hemochromatosis Rheumatism by Anakinra: a Preliminary Phase II Study
Actual Study Start Date : February 4, 2015
Actual Primary Completion Date : September 4, 2018
Actual Study Completion Date : September 4, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hemochromatosis
Drug Information available for: Anakinra

Arm Intervention/treatment
Experimental: Anakinra
One daily subcutaneous injection of a fixed dose of 100 mg will be administered at a fixed time by a nurse during a five day period
Drug: Anakinra
One daily subcutaneous injection of a fixed dose of 100 mg will be administered at a fixed time during a five day period




Primary Outcome Measures :
  1. Rate of patients with improvement of joint pain [ Time Frame: Day 15 ]
    Improvement is defined as the minimal clinically important improvement of joint pain and is assessed on a 0-100 mm visual analogue scale (VAS)


Secondary Outcome Measures :
  1. 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)

  2. 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

  3. 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

  4. Assessment of analgesics consumption [ Time Frame: Day 0, day 15, day 30, day 60, day 90 ]
  5. Assessment of non-steroidal anti-inflammatory drugs (NSAID) consumption [ Time Frame: Day 0, day 15, day 30, day 60, day 90 ]
  6. Assessment of colchicine consumption [ Time Frame: Day 0, day 15, day 30, day 60, day 90 ]
  7. Assessment of steroids injections consumption [ Time Frame: Day 0, day 15, day 30, day 60, day 90 ]
  8. 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

  9. 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

  10. Functional evaluation [ Time Frame: Day 0, day 15, day 30, day 90 ]
    Functional evaluation by WOMAC index for hip and knee

  11. Functional evaluation [ Time Frame: Day 0, day 15, day 30, day 90 ]
    Functional evaluation by Dreiser index for hands

  12. Assessment of joint damage [ Time Frame: Day 0, day 90 ]
    Assessment of joint damage by X-rays and Doppler ultrasound

  13. Synovial fluid analysis [ Time Frame: 3 months ]
    Puncture if acute joint effusion : cells count

  14. Synovial fluid analysis [ Time Frame: 3 months ]
    Puncture if acute joint effusion : search for crystals presence

  15. Synovial fluid analysis [ Time Frame: 3 months ]
    Puncture if acute joint effusion : iron parameters markers

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  21. 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

  22. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02263638


Locations
Layout table for location information
France
CHRU de Lille
Lille, France
Groupe Hospitalier Lariboisière
Paris, France
Rennes University Hospital
Rennes, France, 35033
Sponsors and Collaborators
Rennes University Hospital
Investigators
Layout table for investigator information
Principal Investigator: Pascal Richette Groupe Hospitalier Lariboisière - Paris
Principal Investigator: Pascal Guggenbuhl Rennes University Hospital

Layout table for additonal information
Responsible Party: Rennes University Hospital
ClinicalTrials.gov Identifier: NCT02263638     History of Changes
Other Study ID Numbers: 2014-000609-10
35RC13_8811_THERA ( Other Identifier: Rennes University Hospital )
First Posted: October 13, 2014    Key Record Dates
Last Update Posted: March 12, 2019
Last Verified: March 2019
Keywords provided by Rennes University Hospital:
hereditary haemochromatosis
rheumatism
anakinra
Additional relevant MeSH terms:
Layout table for MeSH terms
Rheumatic Diseases
Hemochromatosis
Collagen Diseases
Metal Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Iron Overload
Iron Metabolism Disorders
Metabolic Diseases
Musculoskeletal Diseases
Connective Tissue Diseases
Interleukin 1 Receptor Antagonist Protein
Antirheumatic Agents