Mevalonate Kinase Deficiency Clinical Trial
Official title:
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.
| Status | Completed |
| Enrollment | 9 |
| Est. completion date | July 2014 |
| Est. primary completion date | July 2014 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 24 Months and older |
| Eligibility |
Inclusion Criteria: 1. Patients with a diagnosis of HIDS proven by DNA analysis and/or enzymatic studies. 2. 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). 3. 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: 1. Pregnant or nursing (lactating) women. 2. History of being immunocompromised, including a positive HIV at screening (ELISA and Western blot) test result. 3. Positive Hepatitis B or Hepatitis C. 4. Live vaccinations within 3 months prior to the start of the trial 5. Positive tuberculosis screening test. Other protocol-defined inclusion/exclusion criteria may apply |
Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| Spain | Novartis Investigative Site | Esplugues de Llobregat | Barcelona |
| Spain | Novartis Investigative Site | Madrid | |
| Spain | Novartis Investigative Site | Valencia | Comunidad Valenciana |
| Lead Sponsor | Collaborator |
|---|---|
| Novartis Pharmaceuticals |
Spain,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Number of Flares Per Participant During Historical Period and Treatment Period | 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. | Historical period, Month 6 (End of treatment period) | No |
| Secondary | Number of Flares Per Participant at During Treatment Period and 24 Month Extension Period | A flare was defined as Physician Global Assessment of HIDS flare severity score of = 2 and a CRP value > 10 mg/L. | Month 6 (End of treatment period), Month 36 (End of Long term treatment Period 2) | No |
| Secondary | Number of Participants Who Flared at Month 6, Month 24 and Month 36 | A flare was defined as Physician Global Assessment of HIDS flare severity score of = 2 and a CRP value > 10 mg/L. | 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) | No |
| Secondary | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | 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. | Any flare event [Baseline up to Month 36 (End of long term treatment period 2)] | No |
| Secondary | Number of Participants With Flare Events Based on Participant Assessed HIDS Flare Severity Score | 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. | 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) | No |
| Secondary | Percentage of Participants With Defined Grades of Participants Assessed Symptom Control | 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. | 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) | No |
| Secondary | Percentage of Participants With Defined Grades of Physician Assessed Symptom Control | 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. | 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) | No |
| Secondary | Percentage of Participants Experiencing Fever as Assessed by Physician's Global Assessment | 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. | 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) | No |
| Secondary | Percentage of Participants Experiencing Apthus Ulcers as Assessed by Physician's Global Assessment | 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. | 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) | No |
| Secondary | Percentage of Participants Experiencing Lymphadenopathy as Assessed by Physician's Global Assessment | 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. | 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) | No |
| Secondary | Percentage of Participants Experiencing Abdominal Pain as Assessed by Physician's Global Assessment | 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. | 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) | No |
| Secondary | Time to Resolution of the Initial Flare After First Canakinumab Treatment | Time to resolution of the initial flare after first dose of canakinumab was determined. | Day 1 (Baseline), Day 28 | No |
| Secondary | Change From Baseline in Inflammation Markers Over Time up to Month 24 | 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. | 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) | No |
| Secondary | Health Assessment Questionnaire (HAQ) Global Score in Adults Over Time | 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). | 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) | No |
| Secondary | Childhood Health Assessment Questionnaire (CHAQ) Global Score in Children Over Time | 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). | 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) | No |
| Secondary | Percentage of Participants Who Received Dose Up-titration During 6-month Treatment Period | 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. | Day 1 up to Month 6 (End of follow up) | No |
| Secondary | Duration of Flares Experienced During the Study | 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. | 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) | No |
| Secondary | Time to Flare After the Last Dose of Canakinumab During the Follow-up Period | 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. | Last dose of canakinumab treatment in follow-up period to end of follow-up period (Day 337) | No |
| Secondary | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | 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. | Day 1 (Start of study treatment) up to Month 36 (End of study) | Yes |
| Secondary | Participants Who Received Rescue Treatment | Participants who experienced flares were treated with corticosteroids and NSAIDs as rescue medication. | Baseline up to Month 36 (End of study) | No |
| Secondary | Serum Concentration-time Profile of Canakinumab | Canakinumab concentrations in serum were assessed for evaluating pharmacokinetics (PK) of the drug. | 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) | No |
| Secondary | Serum Concentration of Total Interleukin-1ß Antibody (IL-1ß) | Pharmacodynamics of canakinumab was assessed by total IL-1ß (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. | 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) | No |
| Secondary | Number of Participants Exhibiting Anti-canakinumab Antibodies at Any Visit | Immunogenicity assessment included determination of anti-canakinumab (ACZ885) antibodies in serum samples using bridging ECLIA assay. | Baseline up to Month 36 (End of study) | No |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
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