TNF-receptor Associated Periodic Syndromes (TRAPS)
Conditions
Keywords
TNF-receptor associated periodic syndrome, fevers, rashes, musculoskeletal and abdominal pain, periorbital edema, TNFR1
Brief summary
This trial will assess the safety and efficacy of ACZ885 in patients with active recurrent or chronic TNF-receptor associated periodic syndrome (TRAPS).
Interventions
DRUGACZ885
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
4 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patient's written informed consent for \>or= 18 years of age before any assessment is performed. Parent or legal guardian's written informed consent and child's assent, if appropriate, are required before any assessment is performed for patients \< 18 years of age. 2. Male and female patients at least 4 years of age at the time of the screening visit. 3. Patients with a clinical diagnosis of TRAPS and a mutation of TNFRSF1A gene. Patients with low penetrance mutations, such as R92Q or P46L, can be included with mutual agreement between the investigator and Novartis. 4. Patients with a diagnosis of recurrent TRAPS must experience more than 6 episodes/year prior to receiving an effective biologic therapy and the duration of each episode lasted at least 8 days. For patients receiving biologic therapy, this criterion applies to prior to receiving the biologic therapy. 5. Patients who have been treated with anakinra must have demonstrated a partial or complete clinical response with an associated decrease in their inflammation markers (CRP and SAA). 6. Active TRAPS as evidenced by clinical signs and symptoms of active TRAPS (Physician's Global Assessment \>or= 2) and an elevated CRP \> 10mg/L (Normal CRP range \<or= 10 mg/L) and/or SAA \> 10 mg/L (Normal SAA range \<or= 10 mg/L) at time of first canakinumab treatment.
Exclusion criteria
1. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (\> 5 mIU/mL). 2. Women of child-bearing potential, defined as pre-menarche females aged 8 years and above or all women physiologically capable of becoming pregnant, UNLESS they are * women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner * women whose partners have been sterilized by vasectomy or other means * using a highly effective method of birth control (i.e. one that results in a less than 1% per year failure rate when used consistently and correctly, such as implants, injectables, combined oral contraceptives, and some intrauterine devices \[IUDs\]; periodic abstinence \[e.g. calendar, ovulation, symptothermal, post-ovulation methods\] is not acceptable) or total abstinence at the discretion of the investigator in cases where the age, career, lifestyle, or sexual orientation of the patient ensures compliance. * Women of child-bearing potential should be willing to use a reliable contraception throughout the study and for 3 months after study drug discontinuation. * Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum FSH levels \> 40 mIU/mL or have had surgical bilateral oophorectomy (with or without hysterectomy) at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential. 3. History of being immunocompromised, including a positive HIV at screening (ELISA and Western blot) test result. 4. Positive QuantiFERON (QFT-TB G In-Tube) test or positive Purified Protein Derivative (PPD) test (\>or= 5 mm induration) at screening or within 2 month prior to the screening visit, according to the national guidelines. Patients with a positive PPD test (\>or= 5 mm induration) at screening may be enrolled only if they have either a negative chest x-ray or a negative QuantiFERON test. 5. Live vaccinations within 3 months prior to the start of the trial, during the trial, and up to 3 months following the last dose. 6. History of significant other medical conditions, which in the Investigator's opinion would exclude the patient from participating in this trial. 7. History of recurrent and/or evidence of active bacterial, fungal, or viral infection(s). 8. Use of prohibited therapies, any other investigational biologics within 8 weeks prior to the Baseline visit, any other investigational drugs, other than investigational biologic treatment, within 30 days (or 3 months for investigational monoclonal antibodies) or 5 half-lives prior to the Baseline visit, whichever is longer 9. History of known hypersensitivity to canakinumab. 10. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Complete or Almost Complete Response at Day 15 | Day 15 | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Complete Clinical Remission at Day 8 and 15 | Day 8 and Day 15 | 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. |
| Percentage of Participant With Target Levels of C-reactive Protein (CRP) and Serum Amyloid A Protein (SAA) at Day 8 and 15 | Day 8 and Day 15 | The CRP and SAA were used as inflammatory markers. The target level concentration was ≤ 10 mg/L. |
| Time to Physician's Assessed Clinical Remission | Baseline up to Day 15 | 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. |
| Percentage of Participants With Complete or Almost Complete Response at Day 15 After Receiving Additional Dose at Day 8 | Day 15 | 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). |
| Time to Participant's Assessed Clinical Remission | Baseline up to Day 15 | 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. |
| Percentage Change From Baseline in C-reactive Protein (CRP) and Serum Amyloid A (SAA) Concentration to End of Study | Day 1 up to Day 953 (End of study) | 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. |
| Percentage of Participants With Defined Grades for Skin Rash, Eye Manifestations, Extremity Pain and Abdominal Pain | Day 113 (end of treatment period) up to Day 925 (End of study) | 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. |
| Percentage of Participants With Complete or Almost Complete Response at Day 8 | Day 8 | 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). |
| Percentage of Participants With Defined Grades in Participant's Global Assessment Score | Day 1 up to Day 253 (End of follow-up period) | 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. |
| Percentage of Relapsed Participants | 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 | 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. |
| Time to Relapse After Last Dose of Canakinumab | Day 85 to Day 253 (End of treatment period to Follow-up period) | 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. |
| Percentage of Participants Who Relapsed and Received Rescue Medication | Day 85 to Day 953 (End of treatment period to End of study) | 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. |
| Serum Concentration of Canakinumab | 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 | Canakinumab concentrations in serum were assessed for evaluating pharmacokinetics of the drug. |
| Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | 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 | 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). |
| Number of Participants With Anti-canakinumab Antibodies at Any Visit | Day 1 up to Day 953 (End of study) | Immunogenicity assessment included determination of anti-canakinumab (ACZ885) antibodies in serum samples using BIAcore system. |
| Percentage of Participants With Defined Grades in Physician's Global Assessment Score | Day 1 up to Day 953 (End of study) | 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. |
Countries
Ireland, Italy, United Kingdom
Participant flow
Recruitment details
The study was conducted at 6 centers in 3 countries.
Pre-assignment details
A total of 29 participants were screened, out of which 20 were enrolled and exposed to study medication. Nine participants were considered as screening failures due to unacceptable laboratory value or test procedure results.
Participants by arm
| Arm | Count |
|---|---|
| Canakinumab Participants received body-weight stratified dosage of canakinumab (2 mg/kg for participants ≤ 40 kg or 150 mg for participants \> 40 kg) through s.c. route as the starting dose at baseline and monthly for 4 months. The dose was escalated at Day 8 if dose of canakinumab was not sufficient to resolve the qualifying TRAPS flare. | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 2 |
Baseline characteristics
| Characteristic | Canakinumab |
|---|---|
| Age, Continuous | 34.62 Years STANDARD_DEVIATION 18.362 |
| Region of Enrollment Ireland | 2 participants |
| Region of Enrollment Italy | 10 participants |
| Region of Enrollment United Kingdom | 8 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 20 / 20 |
| serious Total, serious adverse events | 7 / 20 |
Outcome results
Primary
Percentage of Participants With Complete or Almost Complete Response at Day 15
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).
Time frame: Day 15
Population: The primary analysis was performed on the Full Analysis Set (FAS), defined as all participants who received at least one dose of study treatment and had at least one post-baseline assessment for primary efficacy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Canakinumab | Percentage of Participants With Complete or Almost Complete Response at Day 15 | 95 Percentage of participants |
Secondary
Number of Participants With Anti-canakinumab Antibodies at Any Visit
Immunogenicity assessment included determination of anti-canakinumab (ACZ885) antibodies in serum samples using BIAcore system.
Time frame: Day 1 up to Day 953 (End of study)
Population: The analysis was performed on the FAS population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Canakinumab | Number of Participants With Anti-canakinumab Antibodies at Any Visit | 2 Number of participants |
Secondary
Percentage Change From Baseline in C-reactive Protein (CRP) and Serum Amyloid A (SAA) Concentration to End of Study
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.
Time frame: Day 1 up to Day 953 (End of study)
Population: The analysis was performed on the FAS population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Canakinumab | Percentage Change From Baseline in C-reactive Protein (CRP) and Serum Amyloid A (SAA) Concentration to End of Study | CRP | -92.19 Percent change |
| Canakinumab | Percentage Change From Baseline in C-reactive Protein (CRP) and Serum Amyloid A (SAA) Concentration to End of Study | SAA | -96.54 Percent change |
Secondary
Percentage of Participants Who Relapsed and Received Rescue Medication
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.
Time frame: Day 85 to Day 953 (End of treatment period to End of study)
Population: The analysis was performed on the FAS population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab | Percentage of Participants Who Relapsed and Received Rescue Medication | Corticosteroid | 25 Percentage of participants |
| Canakinumab | Percentage of Participants Who Relapsed and Received Rescue Medication | NSAID | 25 Percentage of participants |
| Canakinumab | Percentage of Participants Who Relapsed and Received Rescue Medication | Both corticosteroid and NSAID | 10 Percentage of participants |
Secondary
Percentage of Participants With Complete Clinical Remission at Day 8 and 15
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.
Time frame: Day 8 and Day 15
Population: The analysis was performed on the FAS population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab | Percentage of Participants With Complete Clinical Remission at Day 8 and 15 | Day 8 | 90 Percentage of participants |
| Canakinumab | Percentage of Participants With Complete Clinical Remission at Day 8 and 15 | Day 15 | 100 Percentage of participants |
Secondary
Percentage of Participants With Complete or Almost Complete Response at Day 15 After Receiving Additional Dose at Day 8
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).
Time frame: Day 15
Population: The analysis was performed on the FAS population. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Canakinumab | Percentage of Participants With Complete or Almost Complete Response at Day 15 After Receiving Additional Dose at Day 8 | 100 Percentage of participants |
Secondary
Percentage of Participants With Complete or Almost Complete Response at Day 8
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).
Time frame: Day 8
Population: The analysis was performed on the FAS population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Canakinumab | Percentage of Participants With Complete or Almost Complete Response at Day 8 | 80 Percentage of participants |
Secondary
Percentage of Participants With Defined Grades for Skin Rash, Eye Manifestations, Extremity Pain and Abdominal Pain
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.
Time frame: Day 113 (end of treatment period) up to Day 925 (End of study)
Population: The analysis was performed on the FAS population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab | Percentage of Participants With Defined Grades for Skin Rash, Eye Manifestations, Extremity Pain and Abdominal Pain | Skin rash absent | 95 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades for Skin Rash, Eye Manifestations, Extremity Pain and Abdominal Pain | Skin rash minimal | 5 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades for Skin Rash, Eye Manifestations, Extremity Pain and Abdominal Pain | Skin rash mild | 0 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades for Skin Rash, Eye Manifestations, Extremity Pain and Abdominal Pain | Skin rash moderate | 0 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades for Skin Rash, Eye Manifestations, Extremity Pain and Abdominal Pain | Skin rash severe | 0 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades for Skin Rash, Eye Manifestations, Extremity Pain and Abdominal Pain | Eye manifestations absent | 90 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades for Skin Rash, Eye Manifestations, Extremity Pain and Abdominal Pain | Eye manifestations minimal | 10 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades for Skin Rash, Eye Manifestations, Extremity Pain and Abdominal Pain | Eye manifestations mild | 0 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades for Skin Rash, Eye Manifestations, Extremity Pain and Abdominal Pain | Eye manifestations moderate | 0 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades for Skin Rash, Eye Manifestations, Extremity Pain and Abdominal Pain | Eye manifestations severe | 0 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades for Skin Rash, Eye Manifestations, Extremity Pain and Abdominal Pain | Extremity pain absent | 90 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades for Skin Rash, Eye Manifestations, Extremity Pain and Abdominal Pain | Extremity pain minimal | 5 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades for Skin Rash, Eye Manifestations, Extremity Pain and Abdominal Pain | Extremity pain mild | 5 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades for Skin Rash, Eye Manifestations, Extremity Pain and Abdominal Pain | Extremity pain moderate | 0 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades for Skin Rash, Eye Manifestations, Extremity Pain and Abdominal Pain | Extremity pain severe | 0 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades for Skin Rash, Eye Manifestations, Extremity Pain and Abdominal Pain | Abdominal pain absent | 95 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades for Skin Rash, Eye Manifestations, Extremity Pain and Abdominal Pain | Abdominal pain minimal | 5 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades for Skin Rash, Eye Manifestations, Extremity Pain and Abdominal Pain | Abdominal pain mild | 0 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades for Skin Rash, Eye Manifestations, Extremity Pain and Abdominal Pain | Abdominal pain moderate | 0 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades for Skin Rash, Eye Manifestations, Extremity Pain and Abdominal Pain | Abdominal pain severe | 0 Percentage of participants |
Secondary
Percentage of Participants With Defined Grades in Participant's Global Assessment Score
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.
Time frame: Day 1 up to Day 253 (End of follow-up period)
Population: The analysis was performed on the FAS population. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab | Percentage of Participants With Defined Grades in Participant's Global Assessment Score | Absent | 41.7 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades in Participant's Global Assessment Score | Minimal | 33.3 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades in Participant's Global Assessment Score | Mild | 8.3 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades in Participant's Global Assessment Score | Moderate | 16.7 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades in Participant's Global Assessment Score | Severe | 0 Percentage of participants |
Secondary
Percentage of Participants With Defined Grades in Physician's Global Assessment Score
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.
Time frame: Day 1 up to Day 953 (End of study)
Population: The analysis was performed on the FAS population. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab | Percentage of Participants With Defined Grades in Physician's Global Assessment Score | None | 84.2 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades in Physician's Global Assessment Score | Minimal | 10.5 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades in Physician's Global Assessment Score | Mild | 0 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades in Physician's Global Assessment Score | Moderate | 0 Percentage of participants |
| Canakinumab | Percentage of Participants With Defined Grades in Physician's Global Assessment Score | Severe | 0 Percentage of participants |
Secondary
Percentage of Participant With Target Levels of C-reactive Protein (CRP) and Serum Amyloid A Protein (SAA) at Day 8 and 15
The CRP and SAA were used as inflammatory markers. The target level concentration was ≤ 10 mg/L.
Time frame: Day 8 and Day 15
Population: The analysis was performed on the FAS population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab | Percentage of Participant With Target Levels of C-reactive Protein (CRP) and Serum Amyloid A Protein (SAA) at Day 8 and 15 | Day 8 | 35 Percentage of participants |
| Canakinumab | Percentage of Participant With Target Levels of C-reactive Protein (CRP) and Serum Amyloid A Protein (SAA) at Day 8 and 15 | Day 15 | 60 Percentage of participants |
Secondary
Percentage of Relapsed Participants
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.
Time frame: 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
Population: The analysis was performed on the FAS population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab | Percentage of Relapsed Participants | Day 421 | 5 Percentage of participants |
| Canakinumab | Percentage of Relapsed Participants | Day 869 | 0 Percentage of participants |
| Canakinumab | Percentage of Relapsed Participants | Day 15 | 0 Percentage of participants |
| Canakinumab | Percentage of Relapsed Participants | Day 29 | 0 Percentage of participants |
| Canakinumab | Percentage of Relapsed Participants | Day 57 | 0 Percentage of participants |
| Canakinumab | Percentage of Relapsed Participants | Day 85 | 5 Percentage of participants |
| Canakinumab | Percentage of Relapsed Participants | Day 113 | 0 Percentage of participants |
| Canakinumab | Percentage of Relapsed Participants | Day 141 | 10 Percentage of participants |
| Canakinumab | Percentage of Relapsed Participants | Day 169 | 10 Percentage of participants |
| Canakinumab | Percentage of Relapsed Participants | Day 197 | 35 Percentage of participants |
| Canakinumab | Percentage of Relapsed Participants | Day 225 | 10 Percentage of participants |
| Canakinumab | Percentage of Relapsed Participants | Day 253 | 10 Percentage of participants |
| Canakinumab | Percentage of Relapsed Participants | Day 281 | 0 Percentage of participants |
| Canakinumab | Percentage of Relapsed Participants | Day 309 | 10 Percentage of participants |
| Canakinumab | Percentage of Relapsed Participants | Day 337 | 5 Percentage of participants |
| Canakinumab | Percentage of Relapsed Participants | Day 365 | 0 Percentage of participants |
| Canakinumab | Percentage of Relapsed Participants | Day 393 | 0 Percentage of participants |
| Canakinumab | Percentage of Relapsed Participants | Day 449 | 0 Percentage of participants |
| Canakinumab | Percentage of Relapsed Participants | Day 477 | 5 Percentage of participants |
| Canakinumab | Percentage of Relapsed Participants | Day 505 | 0 Percentage of participants |
| Canakinumab | Percentage of Relapsed Participants | Day 533 | 0 Percentage of participants |
| Canakinumab | Percentage of Relapsed Participants | Day 561 | 0 Percentage of participants |
| Canakinumab | Percentage of Relapsed Participants | Day 589 | 0 Percentage of participants |
| Canakinumab | Percentage of Relapsed Participants | Day 617 | 0 Percentage of participants |
| Canakinumab | Percentage of Relapsed Participants | Day 645 | 5 Percentage of participants |
| Canakinumab | Percentage of Relapsed Participants | Day 673 | 15 Percentage of participants |
| Canakinumab | Percentage of Relapsed Participants | Day 701 | 0 Percentage of participants |
| Canakinumab | Percentage of Relapsed Participants | Day 729 | 5 Percentage of participants |
| Canakinumab | Percentage of Relapsed Participants | Day 757 | 0 Percentage of participants |
| Canakinumab | Percentage of Relapsed Participants | Day 785 | 0 Percentage of participants |
| Canakinumab | Percentage of Relapsed Participants | Day 813 | 0 Percentage of participants |
| Canakinumab | Percentage of Relapsed Participants | Day 841 | 10 Percentage of participants |
| Canakinumab | Percentage of Relapsed Participants | Day 897 | 10 Percentage of participants |
| Canakinumab | Percentage of Relapsed Participants | Day 925 | 0 Percentage of participants |
| Canakinumab | Percentage of Relapsed Participants | End of Study (Day 953) | 0 Percentage of participants |
Secondary
Serum Concentration of Canakinumab
Canakinumab concentrations in serum were assessed for evaluating pharmacokinetics of the drug.
Time frame: 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
Population: The analysis was performed on the FAS population. The 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Canakinumab | Serum Concentration of Canakinumab | Day 3 (n=20) | 12.737 microgram(s)/milliliter | Standard Deviation 5.3158 |
| Canakinumab | Serum Concentration of Canakinumab | Day 8 (n=19) | 13.874 microgram(s)/milliliter | Standard Deviation 4.5851 |
| Canakinumab | Serum Concentration of Canakinumab | Day 15 (n=19) | 13.609 microgram(s)/milliliter | Standard Deviation 5.5868 |
| Canakinumab | Serum Concentration of Canakinumab | Day 29 (n=20) | 9.911 microgram(s)/milliliter | Standard Deviation 4.2272 |
| Canakinumab | Serum Concentration of Canakinumab | Day 57 (n=20) | 13.605 microgram(s)/milliliter | Standard Deviation 5.4975 |
| Canakinumab | Serum Concentration of Canakinumab | Day 85 (n=20) | 15.291 microgram(s)/milliliter | Standard Deviation 6.4353 |
| Canakinumab | Serum Concentration of Canakinumab | Day 113 (n=20) | 15.837 microgram(s)/milliliter | Standard Deviation 6.828 |
| Canakinumab | Serum Concentration of Canakinumab | Day 141 (n=17) | 8.799 microgram(s)/milliliter | Standard Deviation 3.1486 |
| Canakinumab | Serum Concentration of Canakinumab | Day 169 (n=12) | 5.655 microgram(s)/milliliter | Standard Deviation 2.2158 |
| Canakinumab | Serum Concentration of Canakinumab | Day 197 (n=8) | 3.906 microgram(s)/milliliter | Standard Deviation 1.6446 |
| Canakinumab | Serum Concentration of Canakinumab | Day 225 (n=2) | 2.725 microgram(s)/milliliter | Standard Deviation 1.2799 |
| Canakinumab | Serum Concentration of Canakinumab | Day 253 (n=9) | 10.261 microgram(s)/milliliter | Standard Deviation 7.9592 |
| Canakinumab | Serum Concentration of Canakinumab | Day 281 (n=20) | 9.759 microgram(s)/milliliter | Standard Deviation 4.6194 |
| Canakinumab | Serum Concentration of Canakinumab | Day 309 (n=13) | 13.088 microgram(s)/milliliter | Standard Deviation 4.6648 |
| Canakinumab | Serum Concentration of Canakinumab | Day 337 (n=11) | 13.182 microgram(s)/milliliter | Standard Deviation 5.464 |
| Canakinumab | Serum Concentration of Canakinumab | Day 365 (n=9) | 15.531 microgram(s)/milliliter | Standard Deviation 6.7944 |
| Canakinumab | Serum Concentration of Canakinumab | Day 393 (n=2) | 20.95 microgram(s)/milliliter | Standard Deviation 1.6263 |
| Canakinumab | Serum Concentration of Canakinumab | Day 421 (n=2) | 20.9 microgram(s)/milliliter | Standard Deviation 2.9698 |
| Canakinumab | Serum Concentration of Canakinumab | Day 449 (n=17) | 17.319 microgram(s)/milliliter | Standard Deviation 6.496 |
| Canakinumab | Serum Concentration of Canakinumab | Day 533 (n=1) | 18.4 microgram(s)/milliliter | — |
| Canakinumab | Serum Concentration of Canakinumab | Day 561 (n=4) | 15.55 microgram(s)/milliliter | Standard Deviation 2.2128 |
| Canakinumab | Serum Concentration of Canakinumab | Day 589 (n=5) | 16.48 microgram(s)/milliliter | Standard Deviation 3.8134 |
| Canakinumab | Serum Concentration of Canakinumab | Day 617 (n=17) | 14.124 microgram(s)/milliliter | Standard Deviation 5.8931 |
| Canakinumab | Serum Concentration of Canakinumab | Day 645 (n=1) | 7.45 microgram(s)/milliliter | — |
| Canakinumab | Serum Concentration of Canakinumab | Day 673 (n=5) | 9.802 microgram(s)/milliliter | Standard Deviation 4.6757 |
| Canakinumab | Serum Concentration of Canakinumab | Day 729 (n=5) | 8.912 microgram(s)/milliliter | Standard Deviation 3.4413 |
| Canakinumab | Serum Concentration of Canakinumab | Day 785 (n=18) | 7.757 microgram(s)/milliliter | Standard Deviation 2.2948 |
| Canakinumab | Serum Concentration of Canakinumab | Day 841 (n=4) | 8.528 microgram(s)/milliliter | Standard Deviation 2.112 |
| Canakinumab | Serum Concentration of Canakinumab | Day 897 (n=9) | 8.157 microgram(s)/milliliter | Standard Deviation 2.6782 |
| Canakinumab | Serum Concentration of Canakinumab | Day 925 (n=3) | 10.527 microgram(s)/milliliter | Standard Deviation 7.4405 |
| Canakinumab | Serum Concentration of Canakinumab | Day 953 (n=10) | 9.56 microgram(s)/milliliter | Standard Deviation 2.9375 |
Secondary
Serum Concentration of Total Interleukin-1β Antibody (IL-1β)
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).
Time frame: 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
Population: The analysis was performed on the FAS population. The 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 3 (n=20) | 12.616 pg/mL | Standard Deviation 20.441 |
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 8 (n=19) | 16.811 pg/mL | Standard Deviation 20.237 |
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 15 (n=19) | 10.662 pg/mL | Standard Deviation 7.6915 |
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 29 (n=20) | 9.342 pg/mL | Standard Deviation 5.1266 |
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 57 (n=20) | 10.701 pg/mL | Standard Deviation 4.5329 |
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 85 (n=20) | 11.212 pg/mL | Standard Deviation 4.1552 |
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 113 (n=20) | 14.401 pg/mL | Standard Deviation 5.491 |
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 141 (n=17) | 10.779 pg/mL | Standard Deviation 4.1092 |
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 169 (n=12) | 10.912 pg/mL | Standard Deviation 8.2431 |
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 197 (n=8) | 30.098 pg/mL | Standard Deviation 41.158 |
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 225 (n=2) | 3.52 pg/mL | Standard Deviation 0.9475 |
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 253 (n=9) | 25.002 pg/mL | Standard Deviation 28.274 |
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 281 (n=20) | 13.722 pg/mL | Standard Deviation 7.5574 |
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 309 (n=13) | 22.478 pg/mL | Standard Deviation 16.688 |
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 337 (n=11) | 19.904 pg/mL | Standard Deviation 10.789 |
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 365 (n=9) | 16.338 pg/mL | Standard Deviation 5.8318 |
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 393 (n=2) | 27.6 pg/mL | Standard Deviation 10.182 |
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 421 (n=2) | 30.65 pg/mL | Standard Deviation 12.94 |
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 449 (n=17) | 17.723 pg/mL | Standard Deviation 8.8367 |
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 533 (n=1) | 25.2 pg/mL | — |
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 561 (n=4) | 15.008 pg/mL | Standard Deviation 5.4952 |
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 589 (n=5) | 16.99 pg/mL | Standard Deviation 5.2212 |
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 617 (n=17) | 14.34 pg/mL | Standard Deviation 6.1663 |
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 645 (n=1) | 16 pg/mL | — |
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 673 (n=5) | 15.296 pg/mL | Standard Deviation 11.908 |
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 729 (n=5) | 16.702 pg/mL | Standard Deviation 12.386 |
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 785 (n=18) | 12.698 pg/mL | Standard Deviation 6.0688 |
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 841 (n=4) | 12.478 pg/mL | Standard Deviation 6.9548 |
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 897 (n=9) | 12.331 pg/mL | Standard Deviation 8.032 |
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 925 (n=3) | 15.033 pg/mL | Standard Deviation 1.7502 |
| Canakinumab | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Day 953 (n=10) | 11.701 pg/mL | Standard Deviation 7.9172 |
Secondary
Time to Participant's Assessed Clinical Remission
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.
Time frame: Baseline up to Day 15
Population: The analysis was performed on the FAS population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Canakinumab | Time to Participant's Assessed Clinical Remission | 3 Days |
Secondary
Time to Physician's Assessed Clinical Remission
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.
Time frame: Baseline up to Day 15
Population: The analysis was performed on the FAS population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Canakinumab | Time to Physician's Assessed Clinical Remission | 4 Days |
Secondary
Time to Relapse After Last Dose of Canakinumab
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.
Time frame: Day 85 to Day 253 (End of treatment period to Follow-up period)
Population: The analysis was performed on the FAS population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Canakinumab | Time to Relapse After Last Dose of Canakinumab | 91.5 Days |