Clinical trial NCT01303380: Canakinumab in Patients With Active Hyper-IgD Syndrome
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Mevalonate Kinase Deficiency
Keywords: Hyper IgD syndrome
canakinumab
HIDS
mevalonate kinase deficiency
MKD
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2011-02-24
Enrollment: 9
Sex: ALL
Minimum age (years): 24
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This pilot study is designed to evaluate the efficacy, the safety, and the pharmacokinetics (PK) / pharmacodynamics (PD) of canakinumab treatment in patients with HIDS.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Flares Per Participant During Historical Period and Treatment Period
timeFrame: Historical period, Month 6 (End of treatment period)
Secondary outcomes:
measure: Number of Flares Per Participant at During Treatment Period and 24 Month Extension Period
timeFrame: Month 6 (End of treatment period), Month 36 (End of Long term treatment Period 2)
measure: Number of Participants Who Flared at Month 6, Month 24 and Month 36
timeFrame: 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)
measure: Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score
timeFrame: Any flare event [Baseline up to Month 36 (End of long term treatment period 2)]
measure: Number of Participants With Flare Events Based on Participant Assessed HIDS Flare Severity Score
timeFrame: 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)
measure: Percentage of Participants With Defined Grades of Participants Assessed Symptom Control
timeFrame: 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)
measure: Percentage of Participants With Defined Grades of Physician Assessed Symptom Control
timeFrame: 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)
measure: Percentage of Participants Experiencing Fever as Assessed by Physician's Global Assessment
timeFrame: 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)
measure: Percentage of Participants Experiencing Apthus Ulcers as Assessed by Physician's Global Assessment
timeFrame: 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)
measure: Percentage of Participants Experiencing Lymphadenopathy as Assessed by Physician's Global Assessment
timeFrame: 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)
measure: Percentage of Participants Experiencing Abdominal Pain as Assessed by Physician's Global Assessment
timeFrame: 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)
measure: Time to Resolution of the Initial Flare After First Canakinumab Treatment
timeFrame: Day 1 (Baseline), Day 28
measure: Change From Baseline in Inflammation Markers Over Time up to Month 24
timeFrame: 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)
measure: Health Assessment Questionnaire (HAQ) Global Score in Adults Over Time
timeFrame: 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)
measure: Childhood Health Assessment Questionnaire (CHAQ) Global Score in Children Over Time
timeFrame: 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)
measure: Percentage of Participants Who Received Dose Up-titration During 6-month Treatment Period
timeFrame: Day 1 up to Month 6 (End of follow up)
measure: Duration of Flares Experienced During the Study
timeFrame: 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)
measure: Time to Flare After the Last Dose of Canakinumab During the Follow-up Period
timeFrame: Last dose of canakinumab treatment in follow-up period to end of follow-up period (Day 337)
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Day 1 (Start of study treatment) up to Month 36 (End of study)
measure: Participants Who Received Rescue Treatment
timeFrame: Baseline up to Month 36 (End of study)
measure: Serum Concentration-time Profile of Canakinumab
timeFrame: 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)
measure: Serum Concentration of Total Interleukin-1β Antibody (IL-1β)
timeFrame: 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)
measure: Number of Participants Exhibiting Anti-canakinumab Antibodies at Any Visit
timeFrame: Baseline up to Month 36 (End of study)
Other outcomes:
Locations:
city: Esplugues de Llobregat
country: Spain
facility: Novartis Investigative Site
state: Barcelona
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Madrid
country: Spain
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Arostegui JI, Anton J, Calvo I, Robles A, Iglesias E, Lopez-Montesinos B, Banchereau R, Hong S, Joubert Y, Junge G, Pascual V, Yague J. Open-Label, Phase II Study to Assess the Efficacy and Safety of Canakinumab Treatment in Active Hyperimmunoglobulinemia D With Periodic Fever Syndrome. Arthritis Rheumatol. 2017 Aug;69(8):1679-1688. doi: 10.1002/art.40146. Epub 2017 Jul 5.