SNPMiner Trials by Shray Alag


SNPMiner SNPMiner Trials (Home Page)


Report for Clinical Trial NCT00582907

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

Phase 2 Study of IL-1 Trap (Rilonacept) for Treatment of Familial Mediterranean Fever (FMF)

Familial Mediterranean fever (FMF) is a genetic disease resulting in recurrent attacks of fever, abdominal pain, chest pain, arthritis and rash. There are 5-15% of patients who continue to have FMF attacks despite treatment with colchicine or who cannot tolerate colchicine. Currently there are no alternatives to colchicine. Pyrin, the protein that has a defect in FMF has an important role in the regulation of a molecule called interleukin (IL)-1 beta production and activity. This molecule is very important in the process of inflammation in FMF. Therefore we propose to use IL-1 Trap (Rilonacept), a medication that binds and neutralizes IL-1. We will enroll in this study 17 subjects from the age of 4 years, including adults with active FMF despite colchicine therapy. Subjects will receive in random order two 3-month courses of Rilonacept at 2.2 mg/kg (maximum 160 mg) by weekly subcutaneous injection and two 3-month courses of placebo injection. If patients have at least two FMF attacks during a treatment course they will be able to get if they choose the other treatment until the end of that treatment course. Our hypothesis is that Rilonacept will decrease the number of acute FMF attacks and will be safe to use. This study may confirm the importance of IL-1 in the cause of FMF. Funding source - FDA Office of Orphan Products Development

NCT00582907 Familial Mediterranean Fever
MeSH: Brucellosis Familial Mediterranean Fever Hereditary Autoinflammatory Diseases Fever
HPO: Fever

2 Interventions

Name: Rilonacept

Description: 2.2 mg/kg/wk by subcutaneous injection, for 3 months

Type: Drug

1

Name: Placebo

Description: placebo by subcutaneous injection weekly for 3 months

Type: Drug

2


Primary Outcomes

Description: Difference in number of attacks per treatment month between rilonacept and placebo

Measure: To Assess the Efficacy of Rilonacept in Decreasing the Number of Acute FMF Attacks.

Time: attacks were assessed at the end of each 3 month treatment course (overall up to 6 month of rilonacept and 6 months of placebo, each)

Description: Differences in adverse events (AEs) between rilonacept and placebo per patient-month of treatment. We separately analyzed injection site reactions and infectious adverse events. Other adverse events were too small in number to analyze. The upper table (and first statistical analysis) regards injection site reactions and lower table (and second statistical analysis) regards infections.

Measure: To Determine if There is a Medically Important Difference Between the Safety Profiles of Rilonacept vs. Placebo.

Time: 12 months of entire study length

Secondary Outcomes

Description: This outcome was the difference in days in the length of attacks between rilonacept and placebo.

Measure: To Determine the Difference in the Length of Attacks During Treatment With Rilonacept vs. Placebo.

Time: 12 months

Description: The percentage of rilonacept and placebo treatment courses without FMF attacks.

Measure: Percentage of Treatment Courses Without FMF Attacks in Rilonacept Courses as Compared to Placebo Courses.

Time: Each treatment course of up to 3 months

Description: Differences between rilonacept and placebo in the percentage of courses that attained at least a 50% decrease in FMF attacks when compared to attacks in the screening period.

Measure: To Determine the Proportion of Courses in Which Subjects Attained at Least a 50% Decrease in Acute FMF Attacks During Rilonacept Courses as Compared to Placebo Courses.

Time: Up to 3 months for each treatment course

Description: In a survival analysis we measured the difference (in days) until the development of the first and second attack within a treatment course of up to 3 months and examined differences in this parameter between rilonacept and placebo. Data regarding the development of the second attack are reported below. In regards to the first attack there were no significant differences between rilonacept and placebo (20 days (7.5,>90)for rilonacept; 15 (8,32) for placebo, P=0.066).

Measure: To Determine Differences in the Time to the Development of Attacks Between the Treatment Arms (Rilonacept vs. Placebo).

Time: 3 months

Description: Erythrocyte sedimentation rate - ESR (mm/h)

Measure: To Determine the Differences in the Erythrocyte Sedimentation Rate Between the Treatment Arms (Rilonacept vs. Placebo).

Time: 3 months (each treatment course, overall 12 months)

Description: Differences between the treatment courses in the C-Reactive Protein levels mg/L

Measure: To Determine the Differences in C-Reactive Protein Between the Treatment Arms (Rilonacept vs. Placebo)

Time: 3 months (each treatment course, overall 12 months)

Description: The difference between the treatment arms in the platelet count X 10 to the power of 9

Measure: To Determine the Differences in the Platelet Count Between the Treatment Arms (Rilonacept vs. Placebo)

Time: 3 months (each treatment course, overall 12 months)

Description: The differences between treatment arms in the fibrinogen level (micromol/L)

Measure: To Determine the Differences in the Fibrinogen Levels Between the Treatment Arms (Rilonacept vs. Placebo)

Time: 3 months (each treatment course, overall 12 months)

Description: The difference between the treatment arms in serum amyloid A levels (mg/L)

Measure: To Determine the Differences in Serum Amyloid A Levels Between the Treatment Arms (Rilonacept vs. Placebo)

Time: 3 months (each treatment course, overall 12 months)

Description: Differences in the health-related quality of life (HRQOL) during treatment with rilonacept vs. placebo. HRQOl was measured by the Childhood Health Questionnaire which was adopted also for adults. There are 2 summary scores: 1. Physical summary score. 2. Psychosocial summary score. The data reported below in the upper table is the physical summary composite score and in the lower table the psychosocial summary composite score. Scores were from 0-100 (higher is better) with a score of 50 representing the mean of the normal population.

Measure: To Determine the Differences in the Quality of Life Between the Treatment Arms (Rilonacept vs. Placebo).

Time: 12 months

Description: Differences in the Armenian Evaluation Score between rilonacept and placebo courses. The Armenian Evaluation Score is a composite score of disease severity based on the frequency, duration and character of attacks (degree of fever and severity of serositis). It was adapted to calculate a score for a 3-month treatment course. The lowest (best) score is 0 and higher values are worse. In theory there is no upper limit to the scale. The total score is reported (there are no subscales).

Measure: To Determine the Differences in the FMF Severity Score of the Subjects Between the Treatment Arms (Rilonacept vs. Placebo).

Time: overall 12 months

Description: The proportion of time within the trial that participants received rilonacept as opposed to placebo. The reason for this outcome is that participants who had at least 2 attacks within an individual treatment course were able to "escape" in a blinded manner to the other treatment arm until the end of that treatment course and then resume the original randomization sequence. Thus participants may have been treated for a longer time with one treatment arm or the other.

Measure: To Determine the Differences in the Proportion of Time Subjects Received Rilonacept vs Placebo

Time: 12 months

Purpose: Treatment

Allocation: Randomized

Crossover Assignment


There is one SNP

SNPs


1 E148Q

However, subjects with an isolated heterozygous mutation of exon 2 of the MEFV gene (including E148Q) will not be eligible. --- E148Q ---



HPO Nodes


HPO:
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