Cryopyrin-associated Periodic SyndromesPhase 3NCT01302860
Efficacy, Safety and Tolerability of ACZ885 in Pediatric Patients With the Following Cryopyrin-associated Periodic Syndromes: Familial Cold Autoinflammatory Syndrome, Muckle-Wells Syndrome, or Neonatal Onset Multisystem Inflammatory Disease
A Phase 3 study testing ACZ885 in people with Cryopyrin-associated Periodic Syndromes and Familial Cold Autoinflammatory Syndrome, run by Novartis Pharmaceuticals at 12 sites in 7 countries.
Trial summary
This trial will assess the safety, efficacy and tolerability of ACZ885 in patients aged 4 years and younger with cryopyrin associated periodic syndromes (CAPS) Read more about this study
- Who is it for?
- Ages 1 month to 60 months
- Conditions the study is for
- Cryopyrin-associated Periodic Syndromes, Familial Cold Autoinflammatory Syndrome, Muckle-Wells Syndrome
- What is being tested?
- ACZ885
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 12 sitesin 7 countries
- Study dates
- Nov 2010to Nov 2014
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 month to 60 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Male and female patients that are 28 days up to 60 months of age at the time of the screening visit.
- Body weight > or = 2.5 kg.
- Parent or legal guardian's written informed consent is required before any assessment is performed for patients.
- At study entry, patients should have a clinical diagnosis of FCAS, MWS, or NOMID and symptoms requiring pharmacological intervention. Prior agreement between the Investigator and Novartis for study eligibility is required for patients who do not have a molecular diagnosis of NALP3 mutations available (either testing not performed, or testing performed but negative) upon study entry. For those patients who have not been molecularly tested for NALP3 mutations, molecular testing should be performed during the course of the study.
- For patients treated with an IL-1 blocking agent (i.e. anakinra, rilonacept), these treatments should be discontinued prior to the baseline visit and patients must demonstrate active disease prior to treatment.
- Patients who are scheduled to receive an immunization, according to their local vaccination guidelines, with an inactivated vaccine must be willing to participate in the assessment schedule for vaccinated patients.
Who cannot join
- Preterm neonates for whom, in the Investigator's judgment, participation in the study is not deemed appropriate.
- History of recurrent and/or evidence of active bacterial, fungal, or viral infections (including HIV).
- Patients with immunodeficiency or treatment with immunosuppressive drugs.
- Live vaccinations within < or = 3 months prior to screening. No live vaccinations will be allowed throughout the course of this study and up to 3 months following the last dose.
- Patients with an increased risk of tuberculosis (TB) infection according to following risk factors:
- Patients with recent close contact with persons known to have active pulmonary TB disease
Show all 16Show fewer
- Foreign-born patients from countries with a high prevalence of tuberculosis
- Patients with recent tuberculosis infection (including children > 6 months with a positive PPD test [defined as an induration of at least 10mm])
- Patients with end-stage renal disease
- Patients with diabetes mellitus
- Patients receiving immunosuppressive therapy
- Patients with hematologic cancers.
- Participation in another trial within the last 30 days or 5 half-lives of the investigational compound (whichever is longer).
- Familial and social conditions rendering regular medical assessment not possible.
- Pediatric patients with neutropenia (absolute neutrophil count [ANC] < 1.5 x 10 to the 9th/l)
- Other protocol defined inclusion/exclusion criteria may apply
Trial locations and contacts
12 sites in 7 countries.
12 sites in 7 countries
Germany4 sites
Novartis Investigative Site
Berlin, 13353
Novartis Investigative Site
Dresden, 01307
Novartis Investigative Site
Sankt Augustin, 53757
Novartis Investigative Site
Tübingen, 72076
Belgium2 sites
Novartis Investigative Site
Brussels, 1200
Novartis Investigative Site
Laken, 1020
Spain2 sites
Novartis Investigative Site
Granada, Andalusia, 18012
Novartis Investigative Site
Valencia, Valencia, 46026
About this study
Official title: A One-year Open-label, Multicenter Trial to Assess Efficacy, Safety and Tolerability of Canakinumab (ACZ885) and the Efficacy and Safety of Childhood Vaccinations in Patients Aged 4 Years or Younger With Cryopyrin Associated Periodic Syndromes (CAPS)
This trial will assess the safety, efficacy and tolerability of ACZ885 in patients aged 4 years and younger with cryopyrin associated periodic syndromes (CAPS)
- Conditions
- Cryopyrin-associated Periodic Syndromes, Familial Cold Autoinflammatory Syndrome, Muckle-Wells Syndrome, Neonatal Onset Multisystem Inflammatory Disease
- Being tested
- ACZ885
- Keywords
- Cryopyrin-associated periodic syndromes (CAPS), Familial Cold Autoinflammatory Syndrome (FCAS), Muckle-Wells Syndrome (MWS) or Neonatal Onset Multisystem Inflammatory Disease (NOMID), children, systemic autoinflammatory disease, CIAS-1 gene, NALP-3, NLRP3, ACZ885, Ilaris, human monoclonal anti-human interleukin-1 beta (IL-beta), antibody, autosomal dominant, familial autoinflammatory syndrome
- Medical subject headings
- Cryopyrin-Associated Periodic Syndromes, Multiple Pterygium Syndrome, Autosomal Dominant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ACZ885Drug
| Study group | Role | What they receive |
|---|---|---|
| Canakinumab | Experimental | Canakinumab s.c. injection (2 mg/kg) was administered every 8 weeks. Receives: Drug: ACZ885 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Aged 4 Years or Younger With at Least One Complete Response at Week 56
Complete response was defined as clinical remission and serological remission. Clinical remission was defined as Physician global assessment of auto-inflammatory disease activity as absent or minimal (using a 5-point scale ranging from absent to severe) and assessment of skin disease as absent or minimal (using a 5-point scale ranging from absent to severe). Serological remission was defined as C reactive protein (CRP) or Serum amyloid A protein (SAA) to be less than (<) 15 milligram per liter (mg/L) and <10 mg/L respectively.
Measured: Week 56
Secondary outcomes (8)
Percentage of Participants Aged 2 Years or Younger With at Least One Complete Response at Week 56
Complete response was defined as clinical remission and serological remission. Clinical remission was defined as Physician global assessment of auto-inflammatory disease activity as absent or minimal (using a 5-point scale ranging from absent to severe) and assessment of skin disease as absent or minimal (using a 5-point scale ranging from absent to severe). Serological remission was defined as CRP or SAA to be <15 mg/L and <10 mg/L respectively.
Measured: Week 56
Percentage of Participants With Defined Grades in Physician's Global Assessment Score at Week 56
Participants were assessed based by physician on Physician's Global Assessment measured on a 5--point scale for auto inflammatory disease activity as: 0 = None/absent; 1 = Minimal; 2 = Mild; 3 = Moderate; 4 = Severe.
Measured: Week 56
Percentage of Participants With Defined Grades in Physician Assessment of Skin Disease at Week 56
Participants were assessed by physician for skin disease (urticarial skin rash) measured on a 5--point scale as: 0 = None/absent; 1 = Minimal; 2 = Mild; 3 = Moderate; 4 = Severe.
Measured: Week 56
Change From Baseline in C--Reactive Protein (CRP) and Serum Amyloid A (SAA) Concentrations at Week 56
The CRP and SAA were used as inflammatory markers. The target level concentrations for CRP and SAA was ≤15 mg/L and ≤10 mg/L, respectively. Negative change in concentration of inflammatory markers indicated improvement.
Measured: Baseline, Week 56
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Adverse events (AEs) were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events (SAEs) were defined as any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards.
Measured: Day 1 (start of study treatment) up to Week 56 (end of study)
Percentage of Participants Receiving a Concomitant Vaccination During the Study
Participants received any one of the following inactivated vaccines as per the immunization program: Corynebacterium diphtheria, Bordetella pertussis, Neisseria meningitidis, Clostridium tetani, Influenza type A, Influenza type B, Haemophilus influenza B, Streptococcus pneumoniae, or Hepatitis B were determined.
Measured: Day 1 (start of study treatment) to Week 56 (end of study)
Number of Vaccination Cases With Protective Antibody Levels Following Immunization With Inactivated Vaccines
Participants who received any inactivated vaccines during the study were assessed for their ability to attain protective antibody levels against the vaccine (antigen) post immunization. Participants vaccinations were not assessed for a response if the antibody titre was already sufficient at pre-dose and maintained during the study.
Measured: Day -14 (prior-vaccination), Day 0 (vaccination), Day 28, Day 57 (post-vaccination)
Number of Participants With Anti-canakinumab Antibodies at Week 56
Immunogenicity assessment included determination of anti-canakinumab (ACZ885) antibodies in serum samples using BIAcore system, with detection based on surface plasmon resonance technique.
Measured: Week 56 (End of study)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2011 (estimated)
- Study startNov 2010
- Primary completionNov 2014
- Study completionNov 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cryopyrin-associated Periodic SyndromesStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01302860
- Sponsor's protocol ID
- CACZ885D2307
- Other IDs
- 2009-016859-22, 2009
- Status last verified
- Feb 2017
- First submitted
- 22 Feb 2011
- Last updated
- 29 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Brogan PA, Hofer M, Kuemmerle-Deschner JB, Kone-Paut I, Roesler J, Kallinich T, Horneff G, Calvo Penades I, Sevilla-Perez B, Goffin L, Lauwerys BR, Lachmann HJ, Uziel Y, Wei X, Laxer RM. Rapid and Sustained Long-Term Efficacy and Safety of Canakinumab in Patients With Cryopyrin-Associated Periodic Syndrome Ages Five Years and Younger. Arthritis Rheumatol. 2019 Nov;71(11):1955-1963. doi: 10.1002/art.41004. Epub 2019 Sep 9.
PubMed 31161734
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A One-year Open-label, Multicenter Trial to Assess Efficacy, Safety and Tolerability of Canakinumab (ACZ885) and the Efficacy and Safety of Childhood Vaccinations in Patients Aged 4 Years or Younger With Cryopyrin Associated Periodic Syndromes (CAPS)
- ClinicalTrials.gov ID
- NCT01302860
- Acronym / sponsor ID
- CACZ885D2307
- Conditions
- Cryopyrin-associated Periodic Syndromes, Familial Cold Autoinflammatory Syndrome, Muckle-Wells Syndrome, Neonatal Onset Multisystem Inflammatory Disease
- Keywords
- Cryopyrin-associated periodic syndromes (CAPS), Familial Cold Autoinflammatory Syndrome (FCAS), Muckle-Wells Syndrome (MWS) or Neonatal Onset Multisystem Inflammatory Disease (NOMID), children, systemic autoinflammatory disease, CIAS-1 gene, NALP-3, NLRP3
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Nov 2010
- Primary completion
- Nov 2014 (actual)
- Study completion
- Nov 2014 (actual)
- First posted
- 24 Feb 2011 (estimated)
- Results
- Posted 18 Aug 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This trial will assess the safety, efficacy and tolerability of ACZ885 in patients aged 4 years and younger with cryopyrin associated periodic syndromes (CAPS)
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Canakinumab | Experimental | Drug: ACZ885Canakinumab s.c. injection (2 mg/kg) was administered every 8 weeks. |
Who may qualify
- Ages
- 1 month to 60 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Male and female patients that are 28 days up to 60 months of age at the time of the screening visit.
- Body weight > or = 2.5 kg.
- Parent or legal guardian's written informed consent is required before any assessment is performed for patients.
- At study entry, patients should have a clinical diagnosis of FCAS, MWS, or NOMID and symptoms requiring pharmacological intervention. Prior agreement between the Investigator and Novartis for study eligibility is required for patients who do not have a molecular diagnosis of NALP3 mutations available (either testing not performed, or testing performed but negative) upon study entry. For those patients who have not been molecularly tested for NALP3 mutations, molecular testing should be performed during the course of the study.
- For patients treated with an IL-1 blocking agent (i.e. anakinra, rilonacept), these treatments should be discontinued prior to the baseline visit and patients must demonstrate active disease prior to treatment.
Key exclusion criteria (16 listed)
- Preterm neonates for whom, in the Investigator's judgment, participation in the study is not deemed appropriate.
- History of recurrent and/or evidence of active bacterial, fungal, or viral infections (including HIV).
- Patients with immunodeficiency or treatment with immunosuppressive drugs.
- Live vaccinations within < or = 3 months prior to screening. No live vaccinations will be allowed throughout the course of this study and up to 3 months following the last dose.
- Patients with an increased risk of tuberculosis (TB) infection according to following risk factors:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ACZ885 | Drug | Canakinumab |
Primary outcome
Percentage of Participants Aged 4 Years or Younger With at Least One Complete Response at Week 56
Time frame: Week 56
Complete response was defined as clinical remission and serological remission. Clinical remission was defined as Physician global assessment of auto-inflammatory disease activity as absent or minimal (using a 5-point scale ranging from absent to severe) and assessment of skin disease as absent or minimal (using a 5-point scale ranging from absent to severe). Serological remission was defined as C reactive protein (CRP) or Serum amyloid A protein (SAA) to be less than (<) 15 milligram per liter (mg/L) and <10 mg/L respectively.
8 secondary outcomes
Percentage of Participants Aged 2 Years or Younger With at Least One Complete Response at Week 56
Time frame: Week 56
Percentage of Participants With Defined Grades in Physician's Global Assessment Score at Week 56
Time frame: Week 56
Percentage of Participants With Defined Grades in Physician Assessment of Skin Disease at Week 56
Time frame: Week 56
Change From Baseline in C--Reactive Protein (CRP) and Serum Amyloid A (SAA) Concentrations at Week 56
Time frame: Baseline, Week 56
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Day 1 (start of study treatment) up to Week 56 (end of study)
Percentage of Participants Receiving a Concomitant Vaccination During the Study
Time frame: Day 1 (start of study treatment) to Week 56 (end of study)
Number of Vaccination Cases With Protective Antibody Levels Following Immunization With Inactivated Vaccines
Time frame: Day -14 (prior-vaccination), Day 0 (vaccination), Day 28, Day 57 (post-vaccination)
Number of Participants With Anti-canakinumab Antibodies at Week 56
Time frame: Week 56 (End of study)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31161734Brogan PA, Hofer M, Kuemmerle-Deschner JB, Kone-Paut I, Roesler J, Kallinich T, Horneff G, Calvo Penades I, Sevilla-Perez B, Goffin L, Lauwerys BR, Lachmann HJ, Uziel Y, Wei X, Laxer RM. Rapid and Sustained Long-Term Efficacy and Safety of Canakinumab in Patients With Cryopyrin-Associated Periodic Syndrome Ages Five Years and Younger. Arthritis Rheumatol. 2019 Nov;71(11):1955-1963. doi: 10.1002/art.41004. Epub 2019 Sep 9.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
12 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing ACZ885 in people with Cryopyrin-associated Periodic Syndromes and Familial Cold Autoinflammatory Syndrome, run by Novartis Pharmaceuticals at 12 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Germany, Belgium, Spain, Canada, France and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Aug 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants Aged 4 Years or Younger With at Least One Complete Response at Week 56 (time frame: Week 56). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01302860, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Mar 2017.