| ID | Type | Description | Link |
|---|---|---|---|
| FDA 1RO1FD003435-01 |
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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
Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory genetic disorder resulting in recurrent attacks of fever, serositis, arthritis and rash. Late complications of untreated FMF include the development of renal amyloidosis. FMF is a rare orphan disease in the United States. Treatment with colchicine is effective in reducing the frequency of episodes in most patients and the development of amyloidosis in nearly all patients. However, there are still 5-15% of patients who continue to have acute FMF attacks despite colchicine therapy or are intolerant of colchicine, usually from gastrointestinal adverse effects. Currently there are no effective alternatives to colchicine. Pyrin, the mutated protein in FMF has an important role in the regulation of IL-1 beta production and activity. Mutations in pyrin result in increased IL-1 beta levels in mice and humans. IL-1 beta is an important pro-inflammatory cytokine. Thus, we hypothesize that inhibition of IL-1 will decrease acute attacks in patients with FMF. We propose to use IL-1 Trap (Rilonacept), a fusion protein consisting of human IL-1 cytokine receptor extracellular domains and the FC portion of human IgG1 that binds and neutralizes IL-1.
We will enroll 17 subjects from the age of 4 years, including adults, from multiple centers in the United States with active FMF (at least 1 attack per month) despite receiving at least 1.2-1.5 mg/d of colchicine (dose dependent on age) or are intolerant of colchicine. Subjects will be diagnosed by clinical criteria with at least one heterozygote mutation of the MEFV (pyrin) gene. After screening subjects will be monitored for a month to observe for acute FMF attacks or if they did not develop an attack in that month until they develop two attacks. We will then use a single-subject alternating treatments design with subjects receiving in random order two 3-month courses of Rilonacept at 2.2 mg/kg (max 160 mg) by weekly SC injection and two 3-month courses of comparable volume placebo. Subjects will continue the usual colchicine dose they were on when they started the study. Subjects with 2 acute FMF attacks during a treatment course will be able to crossover to the other treatment arm until the end of that treatment course. There will be 10 study visits: 1. Screening. 2. Treatment baseline after one month or after subjects have developed FMF attacks as described above. After 1 month of each treatment course and at the end of each treatment course (overall 8 visits). At each visit subjects will return completed diary forms, used and unused drug, queried on adverse effects, undergo a physical examination and laboratory tests obtained for inflammation, safety and in some visits for translational studies. Subjects will also fill out quality of life questionnaires and give an overall estimation of the disease activity. Results will be analyzed by traditional frequency statistics (using an intent to treat analysis) and by Bayesian hierarchical modeling. Our primary aim is to assess the efficacy of Rilonacept in decreasing the number of acute FMF attacks while monitoring drug safety.
The significance of the study includes short and long-term benefits. Fewer FMF attacks will result in less functional impairment and a higher quality of life in colchicine resistant or intolerant patients. Once weekly injections have the potential to improve treatment compliance. Fewer acute attacks of arthritis may prevent the development of chronic joint damage. In the long-term, better FMF control may prevent amyloidosis. This study may confirm the importance of IL-1 in the pathogenesis of FMF and provide support for an FDA filing for use of Rilonacept in FMF. The study design may serve as a template for trials of new biologic drugs for rare diseases.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental | Treatment Arm A: Rilonacept (IL-1 Trap) at a dose of 2.2 mg/kg/wk (max 160 mg)given by subcutaneous injection for 3 months plus colchicine at a stable dose for those subjects already taking colchicine, or without colchicine for those intolerant or non-compliant with colchicine. Since the colchicine dose is stable throughout the study for each subject, at the prestudy dose, colchicine was not considered an intervention |
|
| 2 | Placebo Comparator | Treatment Arm B: Placebo given by subcutaneous injection weekly with or without colchicine for 3 months. Since the colchicine dose is stable throughout the study for each subject, at the prestudy dose, colchicine was not considered an intervention. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Rilonacept | Drug | 2.2 mg/kg/wk by subcutaneous injection, for 3 months |
|
| Measure | Description | Time Frame |
|---|---|---|
| To Assess the Efficacy of Rilonacept in Decreasing the Number of Acute FMF Attacks. | Difference in number of attacks per treatment month between rilonacept and placebo | 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) |
| To Determine if There is a Medically Important Difference Between the Safety Profiles of Rilonacept vs. Placebo. | 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. | 12 months of entire study length |
| Measure | Description | Time Frame |
|---|---|---|
| To Determine the Difference in the Length of Attacks During Treatment With Rilonacept vs. Placebo. | This outcome was the difference in days in the length of attacks between rilonacept and placebo. | 12 months |
| Percentage of Treatment Courses Without FMF Attacks in Rilonacept Courses as Compared to Placebo Courses. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Philip J Hashkes, MD, MSc | Shaare Zedek Medical Center/The Cleveland Clinic Foundation | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital Los Angeles/Cedars-Sinai Medical Center | Los Angeles | California | 90027 | United States | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23070486 | Result | Hashkes PJ, Spalding SJ, Giannini EH, Huang B, Johnson A, Park G, Barron KS, Weisman MH, Pashinian N, Reiff AO, Samuels J, Wright DA, Kastner DL, Lovell DJ. Rilonacept for colchicine-resistant or -intolerant familial Mediterranean fever: a randomized trial. Ann Intern Med. 2012 Oct 16;157(8):533-41. doi: 10.7326/0003-4819-157-8-201210160-00003. | |
| 25147819 | Derived | Hashkes PJ, Spalding SJ, Hajj-Ali R, Giannini EH, Johnson A, Barron KS, Weisman MH, Pashinian N, Reiff AO, Samuels J, Wright D, Lovell DJ, Huang B. The effect of rilonacept versus placebo on health-related quality of life in patients with poorly controlled familial Mediterranean fever. Biomed Res Int. 2014;2014:854842. doi: 10.1155/2014/854842. Epub 2014 May 15. |
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Participants had an estimated mean ≥1 FMF attack/month for 3 months before screening, and ≥1 attack/month during screening/run-in period. There was a wash-out period of other biologic medications for those using them at screening. 2 subjects withdrew consent, one lacked mutations and one had insufficient attacks and were excluded before baseline.
Participants were recruited from October 2008 until February 2010. The study was conducted in 6 clinics in the United States in FMF clinics or clinics in regions where a higher prevalence of FMF is expected based on local population ethnicity.
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| ID | Title | Description |
|---|---|---|
| FG000 | Rilonacept-Placebo-Rilonacept-Placebo | Patients received in the randomized sequence above two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine. Overall study was 12 months. |
| FG001 | Rilonacept-Placebo-Placebo-Rilonacept | Patients received in the randomized sequence above two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine. Overall study was 12 months. |
| FG002 | Placebo-Rilonacept-Placebo-Rilonacept | Patients received in the randomized sequence above two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine. |
| FG003 | Placebo-Rilonacept-Rilonacept-Placebo | Patients received in the randomized sequence above two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1st Course |
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| 2nd Course |
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| 3rd Course |
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| 4th Course |
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| ID | Title | Description |
|---|---|---|
| BG000 | All Patients Received Both Rilonacept and Placebo | Patients received in randomized sequences two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine. Patients were randomized to 4 treatment sequences: 1. rilonacept- placebo-rilonacept-placebo; 2. placebo-rilonacept-placebo-rilonacept 3. rilonacept- placebo-placebo-rilonacept and 4. placebo-rilonacept-rilonacept-placebo. Overall length of study for each participant is 12 months. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | To Assess the Efficacy of Rilonacept in Decreasing the Number of Acute FMF Attacks. | Difference in number of attacks per treatment month between rilonacept and placebo | Patients who received at least one complete treatment course and reported attacks were analyzed for the primary outcome measure. | Posted | Median | Inter-Quartile Range | number of attacks per month | 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) |
|
1 year
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Adverse events during placebo treatment. Patients received in randomized sequences two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine. Patients were randomized to 4 treatment sequences: 1. rilonacept- placebo-rilonacept-placebo; 2. placebo-rilonacept-placebo-rilonacept 3. rilonacept- placebo-placebo-rilonacept and 4. placebo-rilonacept-rilonacept-placebo. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hospitalization for FMF attack | Immune system disorders | CTCAE (3.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Injection site reaction | Injury, poisoning and procedural complications | CTCAE (3.0) | Systematic Assessment |
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Philip Hashkes, MD, MSc | Shaare Zedek Medical Center/Cleveland Clinic | 972-2-6555307 | hashkesp@szmc.org.il |
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| ID | Term |
|---|---|
| D010505 | Familial Mediterranean Fever |
| ID | Term |
|---|---|
| D056660 | Hereditary Autoinflammatory Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
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| ID | Term |
|---|---|
| C531377 | rilonacept |
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| Placebo | Drug | placebo by subcutaneous injection weekly for 3 months |
|
The percentage of rilonacept and placebo treatment courses without FMF attacks. |
| Each treatment course of up to 3 months |
| 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. | 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. | Up to 3 months for each treatment course |
| To Determine Differences in the Time to the Development of Attacks Between the Treatment Arms (Rilonacept vs. Placebo). | 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). | 3 months |
| To Determine the Differences in the Erythrocyte Sedimentation Rate Between the Treatment Arms (Rilonacept vs. Placebo). | Erythrocyte sedimentation rate - ESR (mm/h) | 3 months (each treatment course, overall 12 months) |
| To Determine the Differences in C-Reactive Protein Between the Treatment Arms (Rilonacept vs. Placebo) | Differences between the treatment courses in the C-Reactive Protein levels mg/L | 3 months (each treatment course, overall 12 months) |
| To Determine the Differences in the Platelet Count Between the Treatment Arms (Rilonacept vs. Placebo) | The difference between the treatment arms in the platelet count X 10 to the power of 9 | 3 months (each treatment course, overall 12 months) |
| To Determine the Differences in the Fibrinogen Levels Between the Treatment Arms (Rilonacept vs. Placebo) | The differences between treatment arms in the fibrinogen level (micromol/L) | 3 months (each treatment course, overall 12 months) |
| To Determine the Differences in Serum Amyloid A Levels Between the Treatment Arms (Rilonacept vs. Placebo) | The difference between the treatment arms in serum amyloid A levels (mg/L) | 3 months (each treatment course, overall 12 months) |
| To Determine the Differences in the Quality of Life Between the Treatment Arms (Rilonacept vs. Placebo). | 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. | 12 months |
| To Determine the Differences in the FMF Severity Score of the Subjects Between the Treatment Arms (Rilonacept vs. Placebo). | 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). | overall 12 months |
| To Determine the Differences in the Proportion of Time Subjects Received Rilonacept vs Placebo | 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. | 12 months |
| Children's Hospital of Central California |
| Madera |
| California |
| 93638 |
| United States |
| NIH | Bethesda | Maryland | 20892 | United States |
| NYU Hospital for Joint Diseases | New York | New York | 10003 | United States |
| Cleveland Clinic | Cleveland | Ohio | 44195 | United States |
| 24833067 | Derived | Huang B, Giannini EH, Lovell DJ, Ding L, Liu Y, Hashkes PJ. Enhancing crossover trial design for rare diseases: limiting ineffective exposure and increasing study power by enabling patient choice to escape early. Contemp Clin Trials. 2014 Jul;38(2):204-12. doi: 10.1016/j.cct.2014.05.001. Epub 2014 May 12. |
| Lost to Follow-up |
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| COMPLETED |
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| NOT COMPLETED |
|
|
| COMPLETED |
|
| NOT COMPLETED |
|
| COMPLETED |
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| NOT COMPLETED |
|
| Participants |
|
| Age Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Placebo | Patients received in randomized sequences two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine. Patients were randomized to 4 treatment sequences: 1. rilonacept- placebo-rilonacept-placebo; 2. placebo-rilonacept-placebo-rilonacept 3. rilonacept- placebo-placebo-rilonacept and 4. placebo-rilonacept-rilonacept-placebo. Overall length of study for each participant is 12 months. |
|
|
|
| Primary | To Determine if There is a Medically Important Difference Between the Safety Profiles of Rilonacept vs. Placebo. | 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. | Safety analysis included all participants who received at least one dose of medication. | Posted | Median | Inter-Quartile Range | AEs per patient-month of treatment | 12 months of entire study length |
|
|
|
|
| Secondary | To Determine the Difference in the Length of Attacks During Treatment With Rilonacept vs. Placebo. | This outcome was the difference in days in the length of attacks between rilonacept and placebo. | Participants who received any treatment and had recorded attacks | Posted | Median | 95% Confidence Interval | Number of days | 12 months |
|
|
|
|
| Secondary | Percentage of Treatment Courses Without FMF Attacks in Rilonacept Courses as Compared to Placebo Courses. | The percentage of rilonacept and placebo treatment courses without FMF attacks. | Participants who at least one complete treatment course. | Posted | Number | Percentage of courses | Each treatment course of up to 3 months |
|
|
|
|
| Secondary | 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. | 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. | Participants who completed at least one complete treatment course. | Posted | Number | Percentage of courses | Up to 3 months for each treatment course |
|
|
|
|
| Secondary | To Determine Differences in the Time to the Development of Attacks Between the Treatment Arms (Rilonacept vs. Placebo). | 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). | All participants who received an intervention and developed an attack were analyzed. | Posted | Median | Inter-Quartile Range | days until second attack | 3 months |
|
|
|
|
| Secondary | To Determine the Differences in the Erythrocyte Sedimentation Rate Between the Treatment Arms (Rilonacept vs. Placebo). | Erythrocyte sedimentation rate - ESR (mm/h) | Participants who completed at least one treatment course of both rilonacept and placebo. | Posted | Median | Inter-Quartile Range | mm/h | 3 months (each treatment course, overall 12 months) |
|
|
|
|
| Secondary | To Determine the Differences in C-Reactive Protein Between the Treatment Arms (Rilonacept vs. Placebo) | Differences between the treatment courses in the C-Reactive Protein levels mg/L | Patients who received at least one course each of rilonacept and placebo | Posted | Median | Inter-Quartile Range | mg/L | 3 months (each treatment course, overall 12 months) |
|
|
|
|
| Secondary | To Determine the Differences in the Platelet Count Between the Treatment Arms (Rilonacept vs. Placebo) | The difference between the treatment arms in the platelet count X 10 to the power of 9 | The number of patients who received at least one course each of rilonacept and placebo | Posted | Median | Inter-Quartile Range | cell count X10 to the power of 9 | 3 months (each treatment course, overall 12 months) |
|
|
|
|
| Secondary | To Determine the Differences in the Fibrinogen Levels Between the Treatment Arms (Rilonacept vs. Placebo) | The differences between treatment arms in the fibrinogen level (micromol/L) | Patients who received at least one course each of rilonacept and placebo | Posted | Median | Inter-Quartile Range | micromol/L | 3 months (each treatment course, overall 12 months) |
|
|
|
|
| Secondary | To Determine the Differences in Serum Amyloid A Levels Between the Treatment Arms (Rilonacept vs. Placebo) | The difference between the treatment arms in serum amyloid A levels (mg/L) | Patients who received at least one course each of rilonacept and placebo | Posted | Median | Inter-Quartile Range | mg/L | 3 months (each treatment course, overall 12 months) |
|
|
|
|
| Secondary | To Determine the Differences in the Quality of Life Between the Treatment Arms (Rilonacept vs. Placebo). | 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. | Participants who received at least one treatment course of rilonacept and placebo. | Posted | Median | Inter-Quartile Range | Composite HRQOL summary score | 12 months |
|
|
|
|
| Secondary | To Determine the Differences in the FMF Severity Score of the Subjects Between the Treatment Arms (Rilonacept vs. Placebo). | 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). | Participants who received at least one course each of placebo and rilonacept. | Posted | Median | Inter-Quartile Range | units on a scale | overall 12 months |
|
|
|
|
| Secondary | To Determine the Differences in the Proportion of Time Subjects Received Rilonacept vs Placebo | 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. | Participants who received at least one treatment course of both rilonacept and placebo. | Posted | Number | 95% Confidence Interval | Percentage of time treated | 12 months |
|
|
|
|
| 3 |
| 14 |
| 12 |
| 14 |
| EG001 | Rilonacept | Adverse events during rilonacept treatment. Patients received in randomized sequences two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine. Patients were randomized to 4 treatment sequences: 1. rilonacept- placebo-rilonacept-placebo; 2. placebo-rilonacept-placebo-rilonacept 3. rilonacept- placebo-placebo-rilonacept and 4. placebo-rilonacept-rilonacept-placebo. | 3 | 13 | 11 | 13 |
| Pneumonia | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Respiratory Infection | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Upper respiratory infection/Otitis | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Sinusitis | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Herpes labialis | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Herpes Zoster | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Epstein Barr virus | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
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| Hypertension | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Headaches | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Otitis | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Bronchitis | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Influenza | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Arthralgia/bone pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Loss of appetite | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Asthma attack | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Nausea, vomiting | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Heat and cold sensitivity | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Vertigo | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Fracture - toe | Injury, poisoning and procedural complications | CTCAE (3.0) | Systematic Assessment |
|
| Photophobia | Eye disorders | CTCAE (3.0) | Systematic Assessment |
|
| Facial edema | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Fatigue | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Abrasion | Injury, poisoning and procedural complications | CTCAE (3.0) | Systematic Assessment |
|
| Sore throat | Ear and labyrinth disorders | CTCAE (3.0) | Systematic Assessment |
|
| Alanine aminotransferase (ALT) elevation | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Creatine Kinase (CPK) elevation | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Overactive bladder | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
|
| Facial skin infection | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Nose bleed | Ear and labyrinth disorders | CTCAE (3.0) | Systematic Assessment |
|
| Oral thrush | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Conjunctivitis | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
Not provided
Not provided
Null hypothesis: There were no significant differences between rilonacept and placebo in the occurence of infections. No power calculations for this outcome.
| Signed rank |
| 0.13 |
| Median Difference (Net) |
| 0 |
| 2-Sided |
| 95 |
| -0.56 |
| 0.17 |
| No |
| Superiority or Other |
| Signed Rank |
| 0.42 |
| Median Difference (Net) |
| -4.2 |
| 2-Sided |
| 95 |
| -6.8 |
| 3.9 |
| No |
| Superiority or Other |