SNPMiner Trials by Shray Alag


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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 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)


HPO Nodes


Fever
Genes 338
GPC3 RANBP2 ND5 BCL10 BIRC3 CCR1 AK2 TRNW LACC1 PRSS2 ND6 QDPR LIG4 PMP22 JAK2 NLRP3 TCIRG1 TRNV BRCA2 ND4 ERCC2 TET2 RNF168 TREX1 CYP21A2 WIPF1 CFTR LIPA EIF2B2 STXBP2 HLA-B AQP2 IBA57 TRNQ IRF2BP2 HMGCL STAT4 MEFV WT1 EPB41 PML PTS CACNA1S GCH1 G6PD HLA-DRB1 GFI1 PEX6 TET2 SLC29A3 RARA PMM2 ABCC2 TREX1 ERCC4 CRLF1 IFNGR1 NOD2 ND2 TNFAIP3 NLRC4 GPR35 CYBC1 HLA-DPA1 IL12B CHEK2 SLC11A1 MYD88 TRIM28 HLA-B TRNF POU6F2 TBL1XR1 FIP1L1 SPTA1 CALR EIF2B1 BCL2 EIF2B3 CYP11B2 COL1A1 TNFRSF1A BCOR HLA-DPB1 PRSS1 MYD88 BCR MEFV ORAI1 IFIH1 ABL1 TP53 LBR IL10 NTRK1 STX11 IGHM DIS3L2 RYR1 ZFHX2 NOTCH3 SH3KBP1 LPIN1 ACAT1 CASK IL12A-AS1 SLC19A3 IL12A NABP1 CALR PSMB8 IL23R RAG2 TSC1 GALC MST1 IL6 CFH IL2RG AQP2 CYP11B2 ND6 ELP1 RUNX1 NUMA1 SPTB NLRC4 CD3E TMEM165 TCF3 SLC29A3 ATP13A2 ND5 ELANE AVP ALPL STAT3 LIFR SPTB CD247 REST SPTA1 LIFR TNFRSF1A CFHR1 EIF2B5 BLNK HMGCL IGH CPT2 CYBB F5 PTPN22 TRIP13 FOXP1 GAA CYBA RYR1 RAG1 GYPC NLRP3 JAK2 TRNH PSMB9 NCF1 RYR1 SLCO1B1 ND3 CD79B LPIN2 RAG1 HTR1A POMP EIF2B4 SRP54 NLRC4 IRF8 ERAP1 TP53 TRNL1 STAT6 PRNP ND4 NGLY1 LYST ATP1A2 KIF1B HAVCR2 CD3D P4HTM SPINK1 MPL SH2B3 SCYL1 IGH MIF C1R POLR3A DCLRE1C LRRC8A TRNS2 IL7R BCL6 NOD2 NLRP3 GATA2 NGF ATM IL2RG PRKAR1A ADAMTS13 IGLL1 PSTPIP1 NLRP12 KRT18 NLRP3 SPP1 TRNS1 CTLA4 CD79A SLC4A1 IL7R NPM1 AVPR2 RNASEH2B PRKAR1A CFHR3 AVPR2 JAK2 KLHL7 H19 IRF8 MPL HAVCR2 TRIM28 FAS CACNA1S NLRP3 TRNL1 NCF2 SLC12A3 WAS PSMB4 WT1 ND1 HLA-DRB1 TLR4 PTPN22 KCNJ1 COX1 STAT4 MVK ERCC5 IKZF1 CCND1 CFTR ADA2 ND1 CD27 NAB2 XIAP PIK3R1 EDA CHD7 IGH LPIN2 ADAR HLA-DRB1 TRNW HLA-DRB1 COX3 SLC12A1 UNC13D RNASEH2C IL36RN ATP1A3 C1QA STING1 NLRP3 NKX2-1 TCF4 TRNK TSC2 PTPN3 RNASEH2A KLRC4 SCNN1B XPA UBAC2 BTK COL1A1 HLA-B COX2 RAB27A CFTR C4A BCAP31 EPB42 RAG2 IRAK1 PRSS1 DDB2 SCNN1A ELANE HBB DST BTNL2 NLRP1 NCF4 MALT1 TH SCNN1G NLRC4 RB1 MEFV MEFV GLA STAT3 SLCO1B3 ADA ZBTB16 STIM1 ATP6 XPC CTRC ERCC3 KRT8 PRTN3 CTRC CACNA1A RMRP FBP1 SPINK1 ANK1 STAT5B NLRP3 SAMHD1 MLX