Refractory Hemochromatosis RheumatismPhase 2THERANCT02263638
Treatment of Refractory Hemochromatosis Rheumatism by Anakinra: a Preliminary Phase II Study
A Phase 2 study testing Anakinra in people with Refractory Hemochromatosis Rheumatism, run by Rennes University Hospital at 3 sites in France.
Trial summary
Treatment of refractory hemochromatosis rheumatism by Anakinra. Prospective, multicenter, non-randomised, single-arm, open-label, phase II trial. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Refractory Hemochromatosis Rheumatism
- What is being tested?
- Anakinra
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 3 sitesFrance
- Study dates
- 4 Feb 2015to 4 Sep 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
3 sites in 1 country.
France3 sites
CHRU de Lille
Lille
Groupe Hospitalier Lariboisière
Paris
Rennes University Hospital
Rennes, 35033
About this study
Treatment of refractory hemochromatosis rheumatism by Anakinra. Prospective, multicenter, non-randomised, single-arm, open-label, phase II trial.
Read the 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.
- Conditions
- Refractory Hemochromatosis Rheumatism
- Being tested
- Anakinra
- Keywords
- hereditary haemochromatosis, rheumatism, anakinra
- Medical subject headings
- Hemochromatosis, Rheumatic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AnakinraDrug
One daily subcutaneous injection of a fixed dose of 100 mg will be administered at a fixed time during a five day period
| Study group | Role | What they receive |
|---|---|---|
| Anakinra | Experimental | 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 Receives: Drug: Anakinra |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of patients with improvement of joint pain
Improvement is defined as the minimal clinically important improvement of joint pain and is assessed on a 0-100 mm visual analogue scale (VAS)
Measured: Day 15
Secondary outcomes (22)
Assessment of the disease activity
Assessment of the disease activity by Visual analog scale (VAS)
Measured: Day 0, day 15, day 30, day 60, day 90
Assessment of the number of painful joints
Assessment of the number of painful joints by a clinical exam
Measured: Day 0, day 15, day 30, day 60, day 90
Assessment of the number of swollen joints
Assessment of the number of swollen joints by a clinical exam
Measured: Day 0, day 15, day 30, day 60, day 90
Assessment of analgesics consumption
Measured: Day 0, day 15, day 30, day 60, day 90
Assessment of non-steroidal anti-inflammatory drugs (NSAID) consumption
Measured: Day 0, day 15, day 30, day 60, day 90
Assessment of colchicine consumption
Measured: Day 0, day 15, day 30, day 60, day 90
Assessment of steroids injections consumption
Measured: Day 0, day 15, day 30, day 60, day 90
Assessment of the quality of life
Assessment of the quality of life by the SF36 questionnaire
Measured: Day 0, day 15, day 30, day 90
Assessment of the quality of life
Assessment of the quality of life by the HAQ questionnaire
Measured: Day 0, day 15, day 30, day 90
Functional evaluation
Functional evaluation by WOMAC index for hip and knee
Measured: Day 0, day 15, day 30, day 90
Functional evaluation
Functional evaluation by Dreiser index for hands
Measured: Day 0, day 15, day 30, day 90
Assessment of joint damage
Assessment of joint damage by X-rays and Doppler ultrasound
Measured: Day 0, day 90
Synovial fluid analysis
Puncture if acute joint effusion : cells count
Measured: 3 months
Synovial fluid analysis
Puncture if acute joint effusion : search for crystals presence
Measured: 3 months
Synovial fluid analysis
Puncture if acute joint effusion : iron parameters markers
Measured: 3 months
Biological effects on inflammation and iron metabolism
Biological/Vaccine : iron and inflammatory markers
Measured: Day 0, day 15, day 30, day 60, day 90
Time at which Cmax of anakinra was observed (Tmax)
Pharmacokinetics study
Measured: Predose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 15, 18, 21, 24 hours post-dose
Maximum observed concentration (Cmax) of anakinra
Pharmacokinetics study
Measured: Predose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 15, 18, 21, 24 hours post-dose
Half-life (T1/2) of anakinra
Pharmacokinetics study
Measured: Predose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 15, 18, 21, 24 hours post-dose
Area under the concentration-time curve of time 0 to the last detectable concentration (AUC0-last) of anakinra
Pharmacokinetics study
Measured: Predose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 15, 18, 21, 24 hours post-dose
Area under the concentration-time curve of time 0 to infinity (AUC0-∞) of anakinra
Pharmacokinetics study
Measured: Predose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 15, 18, 21, 24 hours post-dose
Plasma clearance after administration (CL/F) of anakinra
Pharmacokinetics study
Measured: Predose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 15, 18, 21, 24 hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2014 (estimated)
- Study start4 Feb 2015
- Primary completion4 Sep 2018
- Study completion4 Sep 2018
Why it stopped: Poor recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Refractory Hemochromatosis RheumatismStudies of the same condition, open and under way.
- More trials run by Rennes University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rennes University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Pascal Richette, Principal investigator, Groupe Hospitalier Lariboisière - ParisPascal Guggenbuhl, Principal investigator, Rennes University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02263638
- Sponsor's protocol ID
- 2014-000609-10
- Other IDs
- 35RC13_8811_THERA, 2014
- Acronym
- THERA
- Status last verified
- Mar 2019
- First submitted
- 23 Sep 2014
- Last updated
- 12 Mar 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Refractory Hemochromatosis Rheumatism by Anakinra: a Preliminary Phase II Study
- ClinicalTrials.gov ID
- NCT02263638
- Acronym / sponsor ID
- THERA / 2014-000609-10
- Conditions
- Refractory Hemochromatosis Rheumatism
- Keywords
- hereditary haemochromatosis, rheumatism, anakinra
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Poor recruitment
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Rennes University HospitalUniversity, hospital or other
- Study start
- 4 Feb 2015 (actual)
- Primary completion
- 4 Sep 2018 (actual)
- Study completion
- 4 Sep 2018 (actual)
- First posted
- 13 Oct 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Treatment of refractory hemochromatosis rheumatism by Anakinra. Prospective, multicenter, non-randomised, single-arm, open-label, phase II trial.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Anakinra | Experimental | Drug: AnakinraOne 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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,
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AnakinraOne daily subcutaneous injection of a fixed dose of 100 mg will be administered at a fixed time during a five day period | Drug | Anakinra |
Primary outcome
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)
22 secondary outcomes
Assessment of the disease activity
Time frame: Day 0, day 15, day 30, day 60, day 90
Assessment of the number of painful joints
Time frame: Day 0, day 15, day 30, day 60, day 90
Assessment of the number of swollen joints
Time frame: Day 0, day 15, day 30, day 60, day 90
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
Time frame: Day 0, day 15, day 30, day 90
Functional evaluation
Time frame: Day 0, day 15, day 30, day 90
Functional evaluation
Time frame: Day 0, day 15, day 30, day 90
Assessment of joint damage
Time frame: Day 0, day 90
Synovial fluid analysis
Time frame: 3 months
Synovial fluid analysis
Time frame: 3 months
Synovial fluid analysis
Time frame: 3 months
Biological effects on inflammation and iron metabolism
Time frame: Day 0, day 15, day 30, day 60, day 90
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
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
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
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
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
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
Results and safety
The study was stopped early (reason given: Poor recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2019.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pascal Richette principal investigator
Groupe Hospitalier Lariboisière - Paris
Pascal Guggenbuhl principal investigator
Rennes University Hospital
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Anakinra in people with Refractory Hemochromatosis Rheumatism, run by Rennes University Hospital at 3 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 12 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Poor recruitment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of patients with improvement of joint pain (time frame: Day 15). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Mar 2019.