Hereditary Periodic Fevers
Conditions
Keywords
Canakinumab, interleukin-1, Hereditary Periodic Fevers, auto-inflammatory diseases
Brief summary
This study is to determine whether canakinumab is able to induce and maintain a clinically meaningful reduction of disease activity in participants with Hereditary Periodic Fevers (HPF) compared to placebo.
Detailed description
This study consists of 3 randomized cohorts (one per condition of colchicine resistant/intolerant Familial Mediterranean Fever (crFMF), Hyper Immunoglobulin D Syndrome (also known as mevalonate kinase deficiency (HIDS/MKD), and Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS), and 4 study epochs: 1. Epoch 1: a screening epoch to assess participant's eligibility; 2. Epoch 2: a randomized treatment epoch of 16 weeks where participants are randomized to canakinumab 150 mg every 4 weeks (q4w) or to placebo to obtain efficacy and safety data in a double-blind placebo controlled parallel-arm setting. This epoch contained 2 possible escape options : 1. early blinded escape option for non responders from Day 8 to Day 28 with here an add-on dose of 150mg canakinumab followed by blinded uptitration at the next scheduled visit (Day 29) 2. late unblinded escape option for non responders from Day 29 to Day 112; with open-label uptitration 3. Epoch 3: a randomized withdrawal epoch of 24 weeks where canakinumab responders from the randomized treatment epoch were re-randomized to canakinumab 150mg q8w or placebo to assess the potential for canakinumab to maintain clinical efficacy at a reduced dosing frequency; 4. Epoch 4: an open-label treatment epoch of 72 weeks to collect long-term
Interventions
DRUGCanakinumab
Canakinumab solution for subcutaneous injection in vial which contained 150mg/mL canakinumab in 1 mL solution.
DRUGPlacebo
Matching placebo to canakinumab solution for subcutaneous injection
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
1 Months to No maximum
Healthy volunteers
No
Inclusion criteria
- Patient's written informed consent (or parent's written informed consent in case of pediatric patient) at screening - Male and female patients at least 2 years of age at the time of the screening visit. Male and female patients \>28 days but \<2 years eligible for open label treatment only. - Confirmed diagnosis and active flare at randomization - CRP \>10mg/L at randomization
Exclusion criteria
- Use of the following therapies (within varying protocol defined timeframes): Corticosteroids, anakinra, canakinumab, rilonacept, tocilizumab, TNF inhibitors, abatacept, tofacitinib, rituximab, leflunomide, thalidomide, cyclosporine, intravenous immunoglobulin, 6-Merceptopurine, azathioprine, cyclophosphamide, or chlorambucil, any other investigational biologics - History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in - situ cervical cancer), treated or untreated - Significant medical diseases, including but not limited to the following: a. History of organ transplantation b. Elevated liver enzymes ≥3x ULN d. Increase in total bilirubin e. Serious hepatic disorder (Child-Pugh scores B or C) f. Chronic Kidney Disease g. Thyroid disease h. Diagnosis of active peptic ulcer disease i. Coagulopathy j. Significant CNS effects including vertigo and dizziness - Any conditions or significant medical problems which immunecompromise the patient and/or places the patient at unacceptable risk for immunomodulatory therapy - Live vaccinations within 3 months prior to the start of the trial, during the trial, and up to 3 months following the last dose
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Resolution of Initial Flare and Absence of New Flares up to the End of the Randomized Treatment Epoch (16 Weeks) | 16 weeks | Resolution of the initial disease flare is defined as: Physician's Global Assessment of Disease activity (PGA) \<2 and C-reactive protein (CRP) within normal range (\<= 10 mg/L) or reduction by at least 70% from baseline. The PGA was evaluated by the investigator based on a 5-point scale: 0 = None (no) disease associated with clinical signs and symptoms; 1 = minimal disease associated signs and symptoms; 2 = mild disease associated signs and symptoms; 3 = moderate disease associated signs and symptoms; and 5 = severe disease associated signs and symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieve Physician's Global Assessment (PGA) < 2 | 16 weeks | The PGA was evaluated by the investigator based on a 5-point scale: 0 = None (no) disease associated with clinical signs and symptoms; 1 = minimal disease associated signs and symptoms; 2 = mild disease associated signs and symptoms; 3 = moderate disease associated signs and symptoms; and 5 = severe disease associated signs and symptoms. |
| Percentage of Participants With the Serologic Remission | 16 weeks | Serologic remission was defined as C-reactive protein \<= 10 mg/L. |
| Percentage of Participants With Normalized Serum Amyloid A (SAA) Level | 16 weeks | Normalized SAA was defined as SAA \<= 10 mg/L. |
| Percentage of Participants of Canakinumab Responders From Epoch 2 Who Maintained a Clinically Meaningful Response (Absence of New Flares) (40 Weeks) | 40 weeks | A responder was defined as a participant who had no flare between week 16 and week 40. |
Countries
Belgium, Canada, France, Germany, Hungary, Ireland, Israel, Italy, Japan, Netherlands, Russia, Spain, Switzerland, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
This study consists of 4 study epochs. A total of 203 participants ((181randomized + 4 non-randomized open-label participants in Epoch 2) + (18 TRAPS rollover participants from ACZ885D2203 (NCT01242813) and ACZ885D2207M in Epoch 3)) have been enrolled into this study.
Pre-assignment details
126 patients, randomized in Epoch 2, were not re-randomized in Epoch 3. These patients were switched to open-label (OL) treatment. Six patients discontinued OL treatment (1 due to physician decision, 1 due to subject/guardian decision, 3 due to lack of efficacy and 1 due to an adverse event).
Participants by arm
| Arm | Count |
|---|---|
| Epoch 2: crFMF: 150 mg During Epoch 2, participants received canakinumab 150mg (or 2mg/kg for participants weighing \<= 40kg) q4w for 16 weeks. If participants were eligible for blinded escape, they received a single add-on dose of canakinumab (150 mg or 2mg/kg for participants weighing \<= 40kg) between day 8 and day 28, and then received blinded uptitration to canakinumab 300 mg q4w from day 29 through day 112. If patients on the highest allowed canakinumab dose of 300 mg (or 4 mg/kg for patients weighing ≤ 40 kg) q4w and re-flared (PGA ≥ 2 and CRP ≥ 30 mg/L) were not eligible for further up-titration. | 31 |
| Epoch 2: crCMF: Placebo During epoch 2, participants received matching placebo to canakinumab 150 mg Participants who required blinded escape,they received a single add-on dose of canakinumab (150 mg or 2mg/kg for participants weighing \<= 40kg) between day 8 and day 28, and then received blinded one dose of placebo and one dose of canakinumab q4w from day 29 through day 112. If flare or re-flare still occurred after receipt of canakinumab.
150mg, participants were uptitrated to open-label canakinumab 300 mg | 32 |
| Epoch 2: HIDS/MKD: 150 mg During Epoch 2, participants received canakinumab 150mg (or 2mg/kg for participants weighing \<= 40kg) q4w for 16 weeks. If participants were eligible for blinded escape, they received a single add-on dose of canakinumab (150 mg or 2mg/kg for participants weighing \<= 40kg) between day 8 and day 28, and then received blinded uptitration to canakinumab 300 mg q4w from day 29 through day 112. If patients on the highest allowed canakinumab dose of 300 mg (or 4 mg/kg for patients weighing ≤ 40 kg) q4w and re-flared (PGA ≥ 2 and CRP ≥ 30 mg/L) were not eligible for further up-titration. | 37 |
| Epoch 2: HIDS/MKD: Placebo During epoch 2, participants received matching placebo to canakinumab 150 mg qw4. Participants who required blinded escape, they received a single add-on dose of canakinumab (150 mg or 2mg/kg for participants weighing \<= 40kg) between day 8 and day 28 and then received blinded one dose of placebo and one dose of canakinumab q4w from day 29 through day 112. If flare or re-flare still occurred after receipt of canakinumab 150mg, participants were uptitrated to open-label canakinumab 300 mg. | 35 |
| Epoch 2: TRAPS: 150 mg During Epoch 2, participants received canakinumab 150mg (or 2mg/kg for participants weighing \<= 40kg) q4w for 16 weeks. If participants were eligible for blinded escape, they received a single add-on dose of canakinumab (150 mg or 2mg/kg for participants weighing \<= 40kg) between day 8 and day 28, and then received blinded uptitration to canakinumab 300 mg q4w from day 29 through day 112. If patients on the highest allowed canakinumab dose of 300 mg (or 4 mg/kg for patients weighing ≤ 40 kg) q4w and re-flared (PGA ≥ 2 and CRP ≥ 30 mg/L) were not eligible for further up-titration | 22 |
| Epoch 2: TRAPS: Placebo During epoch 2, participants received matching placebo to canakinumab 150 mg qw4. Participants who required blinded escape,they received a single add-on dose of canakinumab (150 mg or 2mg/kg for participants weighing \<= 40kg) between Day 8 and 28 and then received blinded one dose of placebo and one dose of canakinumab q4w from day 29 through day 112. If flare or re-flare still occurred after receipt of canakinumab 150mg, participants were uptitrated to open-label canakinumab 300 mg. | 24 |
| Epoch 2: Non-randomized Open Label Treatment - crFMF Canakinumab-naïve Japanese patients with non-exon 10 mutations received open-label canakinumab 150 mg (or 2 mg/kg for patients weighing
≤ 40 kg) q4w | 2 |
| Epoch 2: Non-randomized Open Label HIDS/MKD Participants in the 28 days to less than 2 years old cohort who received open-label canakinumab 150 mg (or 2mg/kg for patients weighing
≤ 40 kg) q4w. | 2 |
| Epoch 2 (Epoch 3) - Non-randomized Open Label TRAPS Open-label treatment in Epoch 3 was initiated for TRAPS patients who rolled over from CACZ885D2203 or CACZ885D2207M. | 18 |
| Total | 203 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 | FG017 | FG018 | FG019 | FG020 | FG021 | FG022 | FG023 | FG024 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Epoch 2 | Adverse Event | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Epoch 2 | Lack of Efficacy | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Epoch 2 | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Epoch 3 | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Epoch 3 | Lack of Efficacy | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Epoch 3 | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Epoch 3 | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Epoch 4 | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Epoch 4 | Lack of Efficacy | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Epoch 4 | Pregnancy | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Epoch 4 | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Epoch 2: Non-randomized Open Label Treatment - crFMF | Epoch 2: crCMF: Placebo | Epoch 2: HIDS/MKD: 150 mg | Epoch 2: TRAPS: Placebo | Epoch 2: crFMF: 150 mg | Epoch 2: HIDS/MKD: Placebo | Epoch 2 (Epoch 3) - Non-randomized Open Label TRAPS | Epoch 2: Non-randomized Open Label HIDS/MKD | Epoch 2: TRAPS: 150 mg | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous crFMF cohort - randomized | NA Years | 18.0 Years FULL_RANGE 13.38 | NA Years | NA Years | 18.0 Years FULL_RANGE 15.02 | NA Years | NA Years | NA Years | NA Years | 18 Years FULL_RANGE 14.1 |
| Age, Continuous crFMF - non-randomized | 24.5 Years | NA Years | NA Years | NA Years | NA Years | NA Years | NA Years | NA Years | NA Years | 24.5 Years |
| Age, Continuous HIDS/MKD cohort - randomized | NA Years | NA Years | 12.0 Years FULL_RANGE 8.49 | NA Years | NA Years | 9.0 Years FULL_RANGE 11.64 | NA Years | NA Years | NA Years | 11.0 Years FULL_RANGE 10.08 |
| Age, Continuous HIDS/MKD - non-randomized | NA Years | NA Years | NA Years | NA Years | NA Years | NA Years | NA Years | 1.0 Years | NA Years | 1.0 Years |
| Age, Continuous roll-over TRAPS - non-randomized | NA Years | NA Years | NA Years | NA Years | NA Years | NA Years | 42.5 Years | NA Years | NA Years | 42.5 Years |
| Age, Continuous TRAPS cohort - randomized | NA Years | NA Years | NA Years | 16.5 Years FULL_RANGE 18.25 | NA Years | NA Years | NA Years | NA Years | 13.5 Years FULL_RANGE 19.22 | 15.5 Years FULL_RANGE 18.55 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 0 Participants | 4 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 11 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 4 Participants | 3 Participants | 2 Participants | 4 Participants | 3 Participants | 2 Participants | 0 Participants | 0 Participants | 18 Participants |
| Race (NIH/OMB) White | 0 Participants | 27 Participants | 34 Participants | 18 Participants | 27 Participants | 31 Participants | 16 Participants | 1 Participants | 20 Participants | 174 Participants |
| Sex: Female, Male Female | 2 Participants | 15 Participants | 24 Participants | 13 Participants | 14 Participants | 19 Participants | 7 Participants | 0 Participants | 10 Participants | 104 Participants |
| Sex: Female, Male Male | 0 Participants | 17 Participants | 13 Participants | 11 Participants | 17 Participants | 16 Participants | 11 Participants | 2 Participants | 12 Participants | 99 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk | EG019 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 18 | 0 / 46 | 0 / 46 | 0 / 46 | 0 / 72 | 0 / 72 | 0 / 72 | 0 / 63 | 0 / 63 | 0 / 63 | 0 / 61 | 0 / 61 | 0 / 61 | 0 / 71 | 0 / 71 | 0 / 71 | 0 / 61 | 0 / 61 | 0 / 61 |
| other Total, other adverse events | 4 / 4 | 18 / 18 | 14 / 46 | 1 / 46 | 43 / 46 | 25 / 72 | 1 / 72 | 68 / 72 | 29 / 63 | 2 / 63 | 54 / 63 | 4 / 61 | 1 / 61 | 61 / 61 | 7 / 71 | 1 / 71 | 70 / 71 | 10 / 61 | 2 / 61 | 56 / 61 |
| serious Total, serious adverse events | 3 / 4 | 1 / 18 | 1 / 46 | 0 / 46 | 8 / 46 | 6 / 72 | 1 / 72 | 16 / 72 | 5 / 63 | 0 / 63 | 16 / 63 | 0 / 61 | 0 / 61 | 9 / 61 | 3 / 71 | 1 / 71 | 18 / 71 | 3 / 61 | 0 / 61 | 17 / 61 |
Outcome results
Primary
Percentage of Participants With Resolution of Initial Flare and Absence of New Flares up to the End of the Randomized Treatment Epoch (16 Weeks)
Resolution of the initial disease flare is defined as: Physician's Global Assessment of Disease activity (PGA) \<2 and C-reactive protein (CRP) within normal range (\<= 10 mg/L) or reduction by at least 70% from baseline. The PGA was evaluated by the investigator based on a 5-point scale: 0 = None (no) disease associated with clinical signs and symptoms; 1 = minimal disease associated signs and symptoms; 2 = mild disease associated signs and symptoms; 3 = moderate disease associated signs and symptoms; and 5 = severe disease associated signs and symptoms.
Time frame: 16 weeks
Population: The Full Analysis Set (FAS), which consisted of all randomized participants in the randomized treatment epoch who received at least one dose of study drug in Epoch 2, was analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Epoch 2: crFMF: 150 mg | Percentage of Participants With Resolution of Initial Flare and Absence of New Flares up to the End of the Randomized Treatment Epoch (16 Weeks) | 61.29 Percentage of participants |
| Epoch 2: crCMF: Placebo | Percentage of Participants With Resolution of Initial Flare and Absence of New Flares up to the End of the Randomized Treatment Epoch (16 Weeks) | 6.25 Percentage of participants |
| Epoch 2: HIDS/MKD: 150 mg | Percentage of Participants With Resolution of Initial Flare and Absence of New Flares up to the End of the Randomized Treatment Epoch (16 Weeks) | 35.14 Percentage of participants |
| Epoch 2: HIDS/MKD: Placebo | Percentage of Participants With Resolution of Initial Flare and Absence of New Flares up to the End of the Randomized Treatment Epoch (16 Weeks) | 5.71 Percentage of participants |
| Epoch 2: TRAPS: 150 mg | Percentage of Participants With Resolution of Initial Flare and Absence of New Flares up to the End of the Randomized Treatment Epoch (16 Weeks) | 45.45 Percentage of participants |
| Epoch 2: TRAPS: Placebo | Percentage of Participants With Resolution of Initial Flare and Absence of New Flares up to the End of the Randomized Treatment Epoch (16 Weeks) | 8.33 Percentage of participants |
p-value: <0.0001Fisher's exact test
p-value: 0.002Fisher's exact test
p-value: 0.005Fisher's exact test
Secondary
Percentage of Participants of Canakinumab Responders From Epoch 2 Who Maintained a Clinically Meaningful Response (Absence of New Flares) (40 Weeks)
A responder was defined as a participant who had no flare between week 16 and week 40.
Time frame: 40 weeks
Population: The re-randomized set was analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Epoch 2: crFMF: 150 mg | Percentage of Participants of Canakinumab Responders From Epoch 2 Who Maintained a Clinically Meaningful Response (Absence of New Flares) (40 Weeks) | 77.8 Percentage of participants |
| Epoch 2: crCMF: Placebo | Percentage of Participants of Canakinumab Responders From Epoch 2 Who Maintained a Clinically Meaningful Response (Absence of New Flares) (40 Weeks) | 30.0 Percentage of participants |
| Epoch 2: HIDS/MKD: 150 mg | Percentage of Participants of Canakinumab Responders From Epoch 2 Who Maintained a Clinically Meaningful Response (Absence of New Flares) (40 Weeks) | 50.0 Percentage of participants |
| Epoch 2: HIDS/MKD: Placebo | Percentage of Participants of Canakinumab Responders From Epoch 2 Who Maintained a Clinically Meaningful Response (Absence of New Flares) (40 Weeks) | 14.3 Percentage of participants |
| Epoch 2: TRAPS: 150 mg | Percentage of Participants of Canakinumab Responders From Epoch 2 Who Maintained a Clinically Meaningful Response (Absence of New Flares) (40 Weeks) | 75.0 Percentage of participants |
| Epoch 2: TRAPS: Placebo | Percentage of Participants of Canakinumab Responders From Epoch 2 Who Maintained a Clinically Meaningful Response (Absence of New Flares) (40 Weeks) | 40.0 Percentage of participants |
p-value: 0.051395% CI: [0.75, 113.44]Regression, Logistic
p-value: 0.216895% CI: [0.27, 366.24]Regression, Logistic
p-value: 0.357195% CI: [0.15, 313.49]Regression, Logistic
Secondary
Percentage of Participants Who Achieve Physician's Global Assessment (PGA) < 2
The PGA was evaluated by the investigator based on a 5-point scale: 0 = None (no) disease associated with clinical signs and symptoms; 1 = minimal disease associated signs and symptoms; 2 = mild disease associated signs and symptoms; 3 = moderate disease associated signs and symptoms; and 5 = severe disease associated signs and symptoms.
Time frame: 16 weeks
Population: The Full Analysis Set (FAS), which consisted of all randomized participants in the randomized treatment epoch who received at least one dose of study drug in Epoch 2, was analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Epoch 2: crFMF: 150 mg | Percentage of Participants Who Achieve Physician's Global Assessment (PGA) < 2 | 64.52 Percentage of participants |
| Epoch 2: crCMF: Placebo | Percentage of Participants Who Achieve Physician's Global Assessment (PGA) < 2 | 9.38 Percentage of participants |
| Epoch 2: HIDS/MKD: 150 mg | Percentage of Participants Who Achieve Physician's Global Assessment (PGA) < 2 | 45.95 Percentage of participants |
| Epoch 2: HIDS/MKD: Placebo | Percentage of Participants Who Achieve Physician's Global Assessment (PGA) < 2 | 5.71 Percentage of participants |
| Epoch 2: TRAPS: 150 mg | Percentage of Participants Who Achieve Physician's Global Assessment (PGA) < 2 | 45.45 Percentage of participants |
| Epoch 2: TRAPS: Placebo | Percentage of Participants Who Achieve Physician's Global Assessment (PGA) < 2 | 4.17 Percentage of participants |
p-value: <0.000195% CI: [4.15, 69.21]Regression, Logistic
p-value: 0.000695% CI: [2.83, 65.59]Regression, Logistic
p-value: 0.002895% CI: [2.52, 224.86]Regression, Logistic
Secondary
Percentage of Participants With Normalized Serum Amyloid A (SAA) Level
Normalized SAA was defined as SAA \<= 10 mg/L.
Time frame: 16 weeks
Population: The Full Analysis Set (FAS), which consisted of all randomized participants in the randomized treatment epoch who received at least one dose of study drug in Epoch 2, was analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Epoch 2: crFMF: 150 mg | Percentage of Participants With Normalized Serum Amyloid A (SAA) Level | 25.81 Percentage of participants |
| Epoch 2: crCMF: Placebo | Percentage of Participants With Normalized Serum Amyloid A (SAA) Level | 0.00 Percentage of participants |
| Epoch 2: HIDS/MKD: 150 mg | Percentage of Participants With Normalized Serum Amyloid A (SAA) Level | 13.51 Percentage of participants |
| Epoch 2: HIDS/MKD: Placebo | Percentage of Participants With Normalized Serum Amyloid A (SAA) Level | 2.86 Percentage of participants |
| Epoch 2: TRAPS: 150 mg | Percentage of Participants With Normalized Serum Amyloid A (SAA) Level | 27.27 Percentage of participants |
| Epoch 2: TRAPS: Placebo | Percentage of Participants With Normalized Serum Amyloid A (SAA) Level | 0.00 Percentage of participants |
p-value: 0.028695% CI: [0.92, 332.92]Regression, Logistic
p-value: 0.077895% CI: [0.53, 51.97]Regression, Logistic
p-value: 0.023595% CI: [1.04, 268.5]Regression, Logistic
Secondary
Percentage of Participants With the Serologic Remission
Serologic remission was defined as C-reactive protein \<= 10 mg/L.
Time frame: 16 weeks
Population: The Full Analysis Set (FAS), which consisted of all randomized participants in the randomized treatment epoch who received at least one dose of study drug in Epoch 2, was analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Epoch 2: crFMF: 150 mg | Percentage of Participants With the Serologic Remission | 67.74 Percentage of participants |
| Epoch 2: crCMF: Placebo | Percentage of Participants With the Serologic Remission | 6.25 Percentage of participants |
| Epoch 2: HIDS/MKD: 150 mg | Percentage of Participants With the Serologic Remission | 40.54 Percentage of participants |
| Epoch 2: HIDS/MKD: Placebo | Percentage of Participants With the Serologic Remission | 5.71 Percentage of participants |
| Epoch 2: TRAPS: 150 mg | Percentage of Participants With the Serologic Remission | 36.36 Percentage of participants |
| Epoch 2: TRAPS: Placebo | Percentage of Participants With the Serologic Remission | 8.33 Percentage of participants |
p-value: <0.000195% CI: [5.86, 151.31]Regression, Logistic
p-value: 0.00195% CI: [2.53, 63.89]Regression, Logistic
p-value: 0.014995% CI: [1.2, 36.57]Regression, Logistic