SNPMiner Trials (Home Page)
Report for Mutation P46L
Developed by Shray Alag, 2020.
SNP Clinical Trial Gene
There is one clinical trial.
Clinical Trials
1 An Open-label, Multicenter, Efficacy and Safety Study of 4-month Canakinumab Treatment With 6-month Follow-up in Patients With Active Recurrent or Chronic TNF-receptor Associated Periodic Syndrome (TRAPS).
This trial will assess the safety and efficacy of ACZ885 in patients with active recurrent or chronic TNF-receptor associated periodic syndrome (TRAPS).
NCT01242813 TNF-receptor Associated Periodic Syndromes (TRAPS) Drug: ACZ885 MeSH:Hereditary Autoinflammatory Diseases Syndrome Fever
HPO:Fever
Patients with low penetrance mutations, such as R92Q or P46L, can be included with mutual agreement between the investigator and Novartis. --- R92Q --- --- P46L ---
Primary Outcomes
Description: Complete response was defined as clinical remission and serological remission. Clinical remission was defined as Physician's Global Assessment of TRAPS activity absent or minimal and serological remission was defined as C reactive protein (CRP) and/or Serum amyloid A protein (SAA) to be less than (<) 10 milligram per liter (mg/L). Almost complete response was defined as clinical remission and a partial serological remission (equal to or more than [≥] 70% reduction of baseline CRP and/or SAA).
Measure: Percentage of Participants With Complete or Almost Complete Response at Day 15 Time: Day 15Secondary Outcomes
Description: Complete response was defined as clinical remission and serological remission. Clinical remission was defined as Physician's Global Assessment of TRAPS activity absent or minimal and serological remission was defined as CRP and/or SAA < 10 mg/L. Almost complete response was defined as clinical remission and a partial serological remission (≥70% reduction of baseline CRP and/or SAA).
Measure: Percentage of Participants With Complete or Almost Complete Response at Day 8 Time: Day 8Description: Complete clinical remission was defined as Physician's Global Assessment of TRAPS activity to be absent or minimal (1). TRAPS associated clinical signs and symptoms were assessed by the investigator at every visit on a 5-point scale: 0 = Absent; 1 = Minimal; 2 = Mild; 3 = Moderate; 4 = Severe.
Measure: Percentage of Participants With Complete Clinical Remission at Day 8 and 15 Time: Day 8 and Day 15Description: The CRP and SAA were used as inflammatory markers. The target level concentration was ≤ 10 mg/L.
Measure: Percentage of Participant With Target Levels of C-reactive Protein (CRP) and Serum Amyloid A Protein (SAA) at Day 8 and 15 Time: Day 8 and Day 15Description: Time period for complete remission after initial canakinumab treatment as assessed by participants was defined as a Physician's Global Assessment of TRAPS symptoms of scale 1 or less. The physician's Global Assessment was based on a 5-point scale: 0 = None/absent ; 1 = Minimal; 2 = Mild; 3 = Moderate; 4 = Severe.
Measure: Time to Physician's Assessed Clinical Remission Time: Baseline up to Day 15Description: Participants who had not achieved a complete response at Day 8 were given an additional dose of canakinumab. Complete response was defined as clinical remission (Physician's Global Assessment of TRAPS activity absent or minimal) and serological remission (CRP and/or SAA < 10 mg/L). Almost complete response was defined as clinical remission and a partial serological remission (≥ 70% reduction of baseline CRP and/or SAA).
Measure: Percentage of Participants With Complete or Almost Complete Response at Day 15 After Receiving Additional Dose at Day 8 Time: Day 15Description: Time period for complete remission after initial canakinumab treatment as assessed by participants was defined as a participant's Global Assessment of TRAPS symptoms of scale 1 or less. The participant's Global Assessment was based on a 5-point scale: 0 = None/absent (no) ; 1 = Minimal; 2 = Mild; 3 = Moderate; 4 = Severe.
Measure: Time to Participant's Assessed Clinical Remission Time: Baseline up to Day 15Description: The CRP and SAA were used as inflammatory markers. The target level concentration was ≤ 10 mg/L. Negative percent change in concentration of inflammatory markers indicated improvement.
Measure: Percentage Change From Baseline in C-reactive Protein (CRP) and Serum Amyloid A (SAA) Concentration to End of Study Time: Day 1 up to Day 953 (End of study)Description: TRAPS signs and symptoms were assessed in 4 key categories: skin disease (skin rash), eye manifestations, extremity pain (musculoskeletal), and abdominal pain. Participants were assessed for TRAPS associated signs and symptoms a 5-point Physician's global assessment scale: None/absent (no); 1 = Minimal; 2 = Mild; 3 = Moderate; 4 = Severe.
Measure: Percentage of Participants With Defined Grades for Skin Rash, Eye Manifestations, Extremity Pain and Abdominal Pain Time: Day 113 (end of treatment period) up to Day 925 (End of study)Description: Participants were assessed based by physician on Physician's Global Assessment measured on a 5-point scale for TRAPS associated signs and symptoms as: 0 = None/absent; 1 = Minimal; 2 = Mild; 3 = Moderate; 4 = Severe.
Measure: Percentage of Participants With Defined Grades in Physician's Global Assessment Score Time: Day 1 up to Day 953 (End of study)Description: Participants assessed the disease condition based on a 5-point participant's global assessment scale based on TRAPS associated signs and symptoms as: 0 = None/absent; 1 = Minimal; 2 = Mild; 3 = Moderate; 4 = Severe.
Measure: Percentage of Participants With Defined Grades in Participant's Global Assessment Score Time: Day 1 up to Day 253 (End of follow-up period)Description: Relapse was defined as a Physician's Global Assessment score of 2 (and an increase of at least 1 point compared to Day 15) and CRP and/or SAA ≥ 30 mg/L representing a 30% increase from Day 15.
Measure: Percentage of Relapsed Participants Time: Day 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365, 393, 421, 449,477,505, 533, 561, 589, 617, 645, 673,701, 729,757, 785, 813, 841,869, 897, 925 and 953Description: Relapse was defined as a Physician's Global Assessment score of 2 (and an increase of at least 1 point compared to Day 15) and CRP and/or SAA ≥ 30 mg/L representing a 30% increase from Day 15.
Measure: Time to Relapse After Last Dose of Canakinumab Time: Day 85 to Day 253 (End of treatment period to Follow-up period)Description: Participants who relapsed after the last dose of canakinumab and received either corticosteroid treatment or NSAID or both corticosteroid treatment and NSAID as rescue medication.
Measure: Percentage of Participants Who Relapsed and Received Rescue Medication Time: Day 85 to Day 953 (End of treatment period to End of study)Description: Canakinumab concentrations in serum were assessed for evaluating pharmacokinetics of the drug.
Measure: Serum Concentration of Canakinumab Time: Day 3, 8, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365, 393, 421, 449, 533, 561, 589, 617, 645, 673, 729, 785, 841, 897, 925 and 953Description: Pharmacodynamics of canakinumab was assessed by total IL-1β (sum of free and bound canakinumab) concentration, determined in serum by means of competitive Enzyme-linked immunosorbent assay (ELISA) with limit of detection at 0.25 picogram/milliliter (pg/mL).
Measure: Serum Concentration of Total Interleukin-1β Antibody (IL-1β) Time: Day 3, 8, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365, 393, 421, 449, 533, 561, 589, 617, 645, 673, 729, 785, 841, 897, 925 and 953Description: Immunogenicity assessment included determination of anti-canakinumab (ACZ885) antibodies in serum samples using BIAcore system.
Measure: Number of Participants With Anti-canakinumab Antibodies at Any Visit Time: Day 1 up to Day 953 (End of study)