- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01303380
Canakinumab in Patients With Active Hyper-IgD Syndrome
October 13, 2015 updated by: Novartis Pharmaceuticals
An Open-label, Multicenter, Efficacy and Safety Pilot Study of 6-month Canakinumab Treatment With up to 6-month Follow-up in Patients With Active Hyper-IgD Syndrome (HIDS)
This pilot study is designed to evaluate the efficacy, the safety, and the pharmacokinetics (PK) / pharmacodynamics (PD) of canakinumab treatment in patients with HIDS.
Study Overview
Study Type
Interventional
Enrollment (Actual)
9
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Madrid, Spain, 28046
- Novartis Investigative Site
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Barcelona
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Esplugues de Llobregat, Barcelona, Spain, 08950
- Novartis Investigative Site
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Comunidad Valenciana
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Valencia, Comunidad Valenciana, Spain, 46026
- Novartis Investigative Site
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
2 years and older (ADULT, OLDER_ADULT, CHILD)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Patients with a diagnosis of HIDS proven by DNA analysis and/or enzymatic studies.
- At time of start of drug treatment: active HIDS as evidenced by a physician global assessment of HIDS flare severity ≥ 2 and CRP values >10 mg/L (normal CRP < or = 10 mg/L).
- Patients who have a history of > or = 3 febrile acute HIDS flares in a 6-month period when not receiving prophylaxis treatment (e.g. anakinra daily treatment) with a duration of each flare lasting > or = 4 days and limiting the normal daily activities.
Exclusion Criteria:
- Pregnant or nursing (lactating) women.
- History of being immunocompromised, including a positive HIV at screening (ELISA and Western blot) test result.
- Positive Hepatitis B or Hepatitis C.
- Live vaccinations within 3 months prior to the start of the trial
- Positive tuberculosis screening test.
Other protocol-defined inclusion/exclusion criteria may apply
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: Canakinumab
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Number of Flares Per Participant During Historical Period and Treatment Period
Time Frame: Historical period, Month 6 (End of treatment period)
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A flare was defined as Physician Global Assessment of HIDS flare severity score of ≥ 2 and a C-reactive protein (CRP) value > 10 mg/L.
Flares during a historical period were defined as most recent 6-months in which the participant has not received treatment for their HIDS other than symptomatic treatment with NSAIDs and/or corticosteroids.
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Historical period, Month 6 (End of treatment period)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Flares Per Participant at During Treatment Period and 24 Month Extension Period
Time Frame: Month 6 (End of treatment period), Month 36 (End of Long term treatment Period 2)
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A flare was defined as Physician Global Assessment of HIDS flare severity score of ≥ 2 and a CRP value > 10 mg/L.
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Month 6 (End of treatment period), Month 36 (End of Long term treatment Period 2)
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Number of Participants Who Flared at Month 6, Month 24 and Month 36
Time Frame: Baseline, Month 6 (End of treatment period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)
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A flare was defined as Physician Global Assessment of HIDS flare severity score of ≥ 2 and a CRP value > 10 mg/L.
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Baseline, Month 6 (End of treatment period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)
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Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score
Time Frame: Any flare event [Baseline up to Month 36 (End of long term treatment period 2)]
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Physician global assessment of severity of HIDS after each flare was based on HIDS flare severity score, a 5- point scale: 0 = Absent signs/symptoms; 1 = Minimal signs/symptoms; 2 = Mild; 3= Moderate; 4 = Severe.
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Any flare event [Baseline up to Month 36 (End of long term treatment period 2)]
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Number of Participants With Flare Events Based on Participant Assessed HIDS Flare Severity Score
Time Frame: Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)
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Participant's global assessment of severity of HIDS after each flare was based on HIDS flare severity score, a 5-point scale: 0 = Absent signs/symptoms; 1 = Minimal signs/symptoms; 2 = Mild; 3= Moderate; 4 = Severe.
Same investigator assessed the same participant throughout the study to ensure consistency between assessments.
Investigators reviewed every participant's diary at each visit after their own clinical assessment.
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Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)
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Percentage of Participants With Defined Grades of Participants Assessed Symptom Control
Time Frame: Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)
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Participants were assessed by participants/parent (participants aged 6-18 years) for control of signs and symptoms associated with HIDS based on 5-point scale: 0 = No control; 1 = Poor control; 2 = Somewhat control; 3 = Good control; and 4= Excellent control.
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Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)
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Percentage of Participants With Defined Grades of Physician Assessed Symptom Control
Time Frame: Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)
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Participants were assessed by physician for control of signs and symptoms associated with HIDS based on 5-point scale: 0 = No control; 1 = Poor control; 2 = Somewhat control; 3 = Good control; and 4= Excellent control.
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Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)
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Percentage of Participants Experiencing Fever as Assessed by Physician's Global Assessment
Time Frame: Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)
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Fever severity was assessed by physician after each flare using a 5-point scale: 0 =Absent signs/symptoms; 1 = Minimal signs/symptoms; 2 = Mild; 3 = Moderate; 4 = Severe.
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Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)
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Percentage of Participants Experiencing Apthus Ulcers as Assessed by Physician's Global Assessment
Time Frame: Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)
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Apthus ulcers were assessed by physician after each flare using a 5-point scale: 0 =Absent signs/symptoms; 1 = Minimal signs/symptoms; 2 = Mild; 3 = Moderate; 4 = Severe.
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Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)
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Percentage of Participants Experiencing Lymphadenopathy as Assessed by Physician's Global Assessment
Time Frame: Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)
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Lymphadenopathy severity was assessed by physician after each flare using a 5-point scale: 0 =Absent signs/symptoms; 1 = Minimal signs/symptoms; 2 = Mild; 3 = Moderate; 4 = Severe.
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Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)
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Percentage of Participants Experiencing Abdominal Pain as Assessed by Physician's Global Assessment
Time Frame: Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)
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Abdominal pain was assessed by physician after each flare using a 5-point scale: 0 =Absent signs/symptoms; 1 = Minimal signs/symptoms; 2 = Mild; 3 = Moderate; 4 = Severe.
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Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)
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Time to Resolution of the Initial Flare After First Canakinumab Treatment
Time Frame: Day 1 (Baseline), Day 28
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Time to resolution of the initial flare after first dose of canakinumab was determined.
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Day 1 (Baseline), Day 28
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Change From Baseline in Inflammation Markers Over Time up to Month 24
Time Frame: Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)
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The C-reactive Protein (CRP) and/or Serum amyloid A protein (SAA) were used as inflammatory markers.
The normal range of CRP was 0-10 mg/L.
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Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)
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Health Assessment Questionnaire (HAQ) Global Score in Adults Over Time
Time Frame: Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)
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Participants were assessed for health-related quality of life (HRQoL) based on Health Assessment Questionnaire (HAQ).
HAQ was an eight 8 categories questionnaire representing all activities related to physical function.
Each category has various sub-categories, which were rated by the participants on a 4- point difficulty scale: 0 = any difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do.
The total score was the mean of the 8 scores, and ranged from 0 (no disability) to 3 (completely disabled).
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Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)
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Childhood Health Assessment Questionnaire (CHAQ) Global Score in Children Over Time
Time Frame: Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)
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Participants or their parents (participants aged 6 to 17 years) were assessed for HRQoL based on Childhood Health Assessment Questionnaire (CHAQ).
CHAQ was an eight domain questionnaire representing functional capacity and independence, evaluated for previous week.
Each domain was rated on a 4-point difficulty scale: 0 = any difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do.The total score is the mean from the 8 scores, and ranges from 0 (no disability) to 3 (completely disabled).
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Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)
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Percentage of Participants Who Received Dose Up-titration During 6-month Treatment Period
Time Frame: Day 1 up to Month 6 (End of follow up)
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Participants who experienced a new HIDS flare between baseline and Week 4 and received an escalated dose of 450 mg of canakinumab every 6 weeks thereafter starting at Week 6 were determined.
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Day 1 up to Month 6 (End of follow up)
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Duration of Flares Experienced During the Study
Time Frame: Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)
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Flare was defined as Physician Global Assessment of HIDS flare severity score of ≥ 2 and a CRP value > 10 mg/L.
The change in post canakinumab treatment flare duration during the study were assessed as compared to historical period.
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Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2)
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Time to Flare After the Last Dose of Canakinumab During the Follow-up Period
Time Frame: Last dose of canakinumab treatment in follow-up period to end of follow-up period (Day 337)
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The median time to flare by the participants after administration of the last dose of canakinumab during the follow-up period was analysed using Kaplan-Meier method.
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Last dose of canakinumab treatment in follow-up period to end of follow-up period (Day 337)
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Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Day 1 (Start of study treatment) up to Month 36 (End of study)
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Adverse events (AEs) were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen.
Serious adverse events (SAEs) were defined as any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalisation, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards.
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Day 1 (Start of study treatment) up to Month 36 (End of study)
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Participants Who Received Rescue Treatment
Time Frame: Baseline up to Month 36 (End of study)
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Participants who experienced flares were treated with corticosteroids and NSAIDs as rescue medication.
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Baseline up to Month 36 (End of study)
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Serum Concentration-time Profile of Canakinumab
Time Frame: Day 1 (Pre-dose), Day 4, Day 15, Day 43, Day 85, Day 127, Day 169 (End of treatment period), Day 197, Day 225, Day 253, Day 281, Day 309, and Day 337 (End of follow-up period) (Post-dose)
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Canakinumab concentrations in serum were assessed for evaluating pharmacokinetics (PK) of the drug.
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Day 1 (Pre-dose), Day 4, Day 15, Day 43, Day 85, Day 127, Day 169 (End of treatment period), Day 197, Day 225, Day 253, Day 281, Day 309, and Day 337 (End of follow-up period) (Post-dose)
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Serum Concentration of Total Interleukin-1β Antibody (IL-1β)
Time Frame: Day 1 (Pre-dose), Day 4, Day 15, Day 43, Day 85, Day 127, Day 169 (End of treatment period), Day 197, Day 225, Day 253, Day 281, Day 309, and Day 337 (End of follow-up period) (Post-dose)
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Pharmacodynamics of canakinumab was assessed by total IL-1β (sum of free and bound canakinumab) concentration, determined in serum by means of sandwich ELISA assay with limit of detection at 0.1 picogram/millilitre.
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Day 1 (Pre-dose), Day 4, Day 15, Day 43, Day 85, Day 127, Day 169 (End of treatment period), Day 197, Day 225, Day 253, Day 281, Day 309, and Day 337 (End of follow-up period) (Post-dose)
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Number of Participants Exhibiting Anti-canakinumab Antibodies at Any Visit
Time Frame: Baseline up to Month 36 (End of study)
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Immunogenicity assessment included determination of anti-canakinumab (ACZ885) antibodies in serum samples using bridging ECLIA assay.
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Baseline up to Month 36 (End of study)
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
March 1, 2011
Primary Completion (ACTUAL)
July 1, 2014
Study Completion (ACTUAL)
July 1, 2014
Study Registration Dates
First Submitted
February 23, 2011
First Submitted That Met QC Criteria
February 23, 2011
First Posted (ESTIMATE)
February 24, 2011
Study Record Updates
Last Update Posted (ESTIMATE)
November 5, 2015
Last Update Submitted That Met QC Criteria
October 13, 2015
Last Verified
October 1, 2015
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Metabolic Diseases
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Immune System Diseases
- Immunoproliferative Disorders
- Hematologic Diseases
- Genetic Diseases, Inborn
- Blood Protein Disorders
- Hereditary Autoinflammatory Diseases
- Metabolism, Inborn Errors
- Brain Diseases, Metabolic
- Brain Diseases, Metabolic, Inborn
- Hypergammaglobulinemia
- Peroxisomal Disorders
- Mevalonate Kinase Deficiency
Other Study ID Numbers
- CACZ885D2402
- 2010-020904-31 (EUDRACT_NUMBER)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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