SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT01242813

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

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)
MeSH: Syndrome Fever Hereditary Autoinflammatory Diseases
HPO: Fever

1 Interventions

Name: ACZ885

Type: Drug

Canakinumab


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 15

Secondary 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 8

Description: 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 15

Description: 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 15

Description: 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 15

Description: 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 15

Description: 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 15

Description: 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 953

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: 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 953

Description: 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 953

Description: 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)

Purpose: Treatment

Single Group Assignment


There are 2 SNPs

SNPs


1 P46L

Patients with low penetrance mutations, such as R92Q or P46L, can be included with mutual agreement between the investigator and Novartis. --- R92Q --- --- P46L ---


2 R92Q

Patients with low penetrance mutations, such as R92Q or P46L, can be included with mutual agreement between the investigator and Novartis. --- R92Q ---



HPO Nodes


HPO:
Fever
Genes 252
CYBB IL10 TET2 MYD88 IL12A IL12B PRSS1 TREX1 IBA57 NLRP12 POU6F2 SLC29A3 ERCC2 GALC ERCC3 ERCC4 ZBTB16 ABL1 ERCC5 PRTN3 DIS3L2 CRLF1 RNF168 HLA-B SPINK1 ACAT1 AVP ERAP1 HLA-DPA1 AVPR2 HLA-DPB1 CYP11B2 TMEM165 HLA-DRB1 SPTA1 CYP21A2 CYBC1 SPTB CFTR NCF1 PSMB4 GATA2 BLNK PSMB8 SCYL1 PSMB9 PEX6 TCIRG1 SRP54 SLCO1B3 UNC13D PTPN22 IKZF1 NCF2 TSC1 NCF4 TSC2 CCND1 GCH1 HMGCL BCL2 TMEM173 BCL6 ADA BCR ADAR TRIP13 ADA2 F5 LYST DDB2 KLRC4 GFI1 MEFV NLRC4 RYR1 STAT3 STAT4 STAT5B NOD2 STIM1 JAK2 LPIN1 IFIH1 MALT1 PTPN3 DST FBP1 GLA STXBP2 GPC3 BRCA2 KLHL7 POMP PTS KCNJ1 PIK3R1 BTK RNASEH2C EIF2B4 MIF EIF2B3 EIF2B2 EIF2B5 SCNN1A SCNN1B NGF SCNN1G FIP1L1 AK2 CCR1 C4A BCL10 ABCC2 NME1 QDPR RAB27A IL23R NOTCH3 ALPL PML COL1A1 PMM2 MPL PMP22 RNASEH2B CACNA1A NPM1 RAG1 RAG2 CACNA1S TCF4 RANBP2 KRT8 TCF3 HTR1A RARA ANK1 WAS WIPF1 MLX SH2B3 KRT18 RB1 RNASEH2A CALR GPR35 NTRK1 SH3KBP1 NUMA1 SLC19A3 IRF8 WT1 ELP1 BIRC3 XIAP SAMHD1 XPA CHD7 XPC ADAMTS13 LBR REST PSTPIP1 NABP1 RUNX1 FAS AQP2 SLCO1B1 TBL1XR1 EDA ATP13A2 NLRP3 POLR3A SLC4A1 CASK IFNGR1 HAVCR2 MST1 RMRP LIFR ORAI1 LIG4 TH LIPA BCAP31 ATP6 SLC11A1 IL36RN SLC12A1 SLC12A3 COX1 COX2 COX3 IGH DCLRE1C LACC1 CD27 TRIM28 IL12A-AS1 EIF2B1 GYPC IGHM BTNL2 ND1 ND2 ND3 ND4 TLR4 ND5 ND6 LPIN2 CHEK2 PRKAR1A LRRC8A ELANE ZFHX2 CD79A CD79B UBAC2 FOXP1 TRNF TRNH CTLA4 TRNK IGLL1 TRNL1 ATM NGLY1 TNFAIP3 TRNQ TNFRSF1A ATP1A2 ATP1A3 TRNS1 TRNS2 TRNV TRNW HBB STX11 IL2RG G6PD IL6 EPB41 GAA H19 PRNP TP53 EPB42 MVK IL7R CYBA