Clinical trial NCT01242813: Efficacy and Safety Study of ACZ885 in Patients With Active Recurrent or Chronic TNF-receptor Associated Periodic Syndrome (TRAPS).
Official title: An Open-label, Multicenter, Efficacy and Safety Study of 4-month Canakinumab Treatment With 6-month Follow-up in Patients With Active Recurrent or Chronic TNF-receptor Associated Periodic Syndrome (TRAPS).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: TNF-receptor Associated Periodic Syndromes (TRAPS)
Keywords: TNF-receptor associated periodic syndrome
fevers
rashes
musculoskeletal and abdominal pain
periorbital edema
TNFR1
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2010-11-17
Enrollment: 20
Sex: ALL
Minimum age (years): 4
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


Eligibility criteria: 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/exclusion criteria may apply.

Primary outcomes:
measure: Percentage of Participants With Complete or Almost Complete Response at Day 15
timeFrame: Day 15
Secondary outcomes:
measure: Percentage of Participants With Complete or Almost Complete Response at Day 8
timeFrame: Day 8
measure: Percentage of Participants With Complete Clinical Remission at Day 8 and 15
timeFrame: Day 8 and Day 15
measure: Percentage of Participant With Target Levels of C-reactive Protein (CRP) and Serum Amyloid A Protein (SAA) at Day 8 and 15
timeFrame: Day 8 and Day 15
measure: Time to Physician's Assessed Clinical Remission
timeFrame: Baseline up to Day 15
measure: Percentage of Participants With Complete or Almost Complete Response at Day 15 After Receiving Additional Dose at Day 8
timeFrame: Day 15
measure: Time to Participant's Assessed Clinical Remission
timeFrame: Baseline up to Day 15
measure: Percentage Change From Baseline in C-reactive Protein (CRP) and Serum Amyloid A (SAA) Concentration to End of Study
timeFrame: Day 1 up to Day 953 (End of study)
measure: Percentage of Participants With Defined Grades for Skin Rash, Eye Manifestations, Extremity Pain and Abdominal Pain
timeFrame: Day 113 (end of treatment period) up to Day 925 (End of study)
measure: Percentage of Participants With Defined Grades in Physician's Global Assessment Score
timeFrame: Day 1 up to Day 953 (End of study)
measure: Percentage of Participants With Defined Grades in Participant's Global Assessment Score
timeFrame: Day 1 up to Day 253 (End of follow-up period)
measure: Percentage of Relapsed Participants
timeFrame: 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
measure: Time to Relapse After Last Dose of Canakinumab
timeFrame: Day 85 to Day 253 (End of treatment period to Follow-up period)
measure: Percentage of Participants Who Relapsed and Received Rescue Medication
timeFrame: Day 85 to Day 953 (End of treatment period to End of study)
measure: Serum Concentration of Canakinumab
timeFrame: 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
measure: Serum Concentration of Total Interleukin-1β Antibody (IL-1β)
timeFrame: 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
measure: Number of Participants With Anti-canakinumab Antibodies at Any Visit
timeFrame: Day 1 up to Day 953 (End of study)
Other outcomes:
Locations:
city: Galway
country: Ireland
facility: Novartis Investigative Site
city: Sciacca
country: Italy
facility: Novartis Investigative Site
state: AG
city: Brescia
country: Italy
facility: Novartis Investigative Site
state: BS
city: Genova
country: Italy
facility: Novartis Investigative Site
state: GE
city: Pavia
country: Italy
facility: Novartis Investigative Site
state: PV
city: London
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Torene R, Nirmala N, Obici L, Cattalini M, Tormey V, Caorsi R, Starck-Schwertz S, Letzkus M, Hartmann N, Abrams K, Lachmann H, Gattorno M. Canakinumab reverses overexpression of inflammatory response genes in tumour necrosis factor receptor-associated periodic syndrome. Ann Rheum Dis. 2017 Jan;76(1):303-309. doi: 10.1136/annrheumdis-2016-209335. Epub 2016 Jul 29.
citation: Gattorno M, Obici L, Cattalini M, Tormey V, Abrams K, Davis N, Speziale A, Bhansali SG, Martini A, Lachmann HJ. Canakinumab treatment for patients with active recurrent or chronic TNF receptor-associated periodic syndrome (TRAPS): an open-label, phase II study. Ann Rheum Dis. 2017 Jan;76(1):173-178. doi: 10.1136/annrheumdis-2015-209031. Epub 2016 Jun 7.