SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT00582907

Developed by Shray Alag, 2019.
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: Fever Brucellosis Familial Mediterranean Fever Hereditary Autoinflammatory Diseases
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 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