Efficacy and Safety Study of ACZ885 in Patients With Active Recurrent or Chronic TNF-receptor Associated Periodic Syndrome (TRAPS).

NCT01242813 | Completed Phase 2 Results

• 2 other identifiers: CACZ885D22032010-020061-24
• Study Type: interventional
• Target: 20
• Locations: 3 countries
• Sites: 6

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).

Conditions

TNF-receptor Associated Periodic Syndromes (TRAPS)

Keywords

TNF-receptor associated periodic syndrome; fevers; rashes; musculoskeletal and abdominal pain; periorbital edema; TNFR1

Outcome Measures

Primary Outcomes (1)

• 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).

  Day 15

Secondary Outcomes (16)

• Percentage of Participants With Complete or Almost Complete Response at Day 8

  Day 8

• Percentage of Participants With Complete Clinical Remission at Day 8 and 15

  Day 8 and Day 15

• 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

• Time to Physician's Assessed Clinical Remission

  Baseline up to Day 15

• Percentage of Participants With Complete or Almost Complete Response at Day 15 After Receiving Additional Dose at Day 8

  Day 15

Study Arms (1)

Canakinumab

EXPERIMENTAL

This was an open-label, single treatment arm, multicenter study of monthly canakinumab 150 mg (2 mg/kg for patient ≤ 40 kg) subcutaneous injections in patients with active recurrent or chronic TRAPS.

Drug: ACZ885

Interventions

ACZ885 DRUG

Canakinumab

Eligibility Criteria

• Age: 4 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Male and female patients at least 4 years of age at the time of the screening visit.
• 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.
• 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.
• 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).
• 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.

You may not qualify if:

• 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).
• 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.
• History of being immunocompromised, including a positive HIV at screening (ELISA and Western blot) test result.
• 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.
• Live vaccinations within 3 months prior to the start of the trial, during the trial, and up to 3 months following the last dose.
• History of significant other medical conditions, which in the Investigator's opinion would exclude the patient from participating in this trial.
• History of recurrent and/or evidence of active bacterial, fungal, or viral infection(s).
• 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
• History of known hypersensitivity to canakinumab.
• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (6)

Novartis Investigative Site

Galway, Ireland, Ireland

Location

Novartis Investigative Site

Sciacca, AG, 92019, Italy

Location

Novartis Investigative Site

Brescia, BS, 25123, Italy

Location

Novartis Investigative Site

Genova, GE, 16147, Italy

Location

Novartis Investigative Site

Pavia, PV, 27100, Italy

Location

Novartis Investigative Site

London, NW3 2QG, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 27474763 DERIVED

• 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.

  PMID: 27269295 DERIVED

MeSH Terms

Conditions

Periodic fever, familial, autosomal dominant; Fever; Exanthema; Abdominal Pain; Orbital Cellulitis

Interventions

canakinumab

Condition Hierarchy (Ancestors)

Body Temperature Changes; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Skin Diseases; Skin and Connective Tissue Diseases; Pain; Neurologic Manifestations; Signs and Symptoms, Digestive; Orbital Diseases; Eye Diseases; Cellulitis; Connective Tissue Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2010
• First Posted: November 17, 2010
• Study Start: October 1, 2010
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: February 4, 2016
• Results First Posted: February 4, 2016

Record last verified: 2016-01

Locations

GB (1); IT (4); IE (1)