Cryopyrin-associated Periodic SyndromesPhase 3NCT01576367
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 provide long-term safety, efficacy and tolerability of ACZ885 in CAPS patients that completed the CACZ885D2307 study Read more about this study
- Who is it for?
- Ages 1 year to 4 years
- Conditions the study is for
- Cryopyrin-associated Periodic Syndromes, Familial Cold Autoinflammatory Syndrome, Muckle-Wells Syndrome
- What is being tested?
- ACZ885
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 12 sitesin 7 countries
- Study dates
- 16 Jan 2012to 13 Oct 2015
- 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 year to 4 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Patients who completed the core CACZ885D2307 study (a patient is defined as having completed the core study if they completed the study up to and including the EOS visit with no major protocol deviations in the core).
- Male and female patients that are ≥ 1 year of age at the time of the roll-over visit.
- Parent or legal guardian written informed consent must be obtained before any assessment in the extension CACZ885D2307E1 study is performed.
Who cannot join
- Patients for who continued treatment in the CACZ885D2307E1 extension study is not considered appropriate by the treating physician.
- Patients who discontinued from the core CACZ885D2307 study
- 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
Saint 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: An Open-label Extension Study to Assess Efficacy, Safety and Tolerability of Canakinumab and the Efficacy and Safety of Childhood Vaccinations in Patients With Cryopyrin Associated Periodic Syndromes (CAPS)
This trial will provide long-term safety, efficacy and tolerability of ACZ885 in CAPS patients that completed the CACZ885D2307 study
- 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), Neonatal Onset Multisystem Inflammatory Disease (NOMID), children, systemic autoinflammatory disease, CIAS-1 gene, NALP-3, NLRP3, ACZ885, canakinumab, human monoclonal anti-human interleukin-1 antibody, autosomal dominant, familial autoinflammatory syndrome, childhood immunizations vaccinations
- 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.
ACZ885Biological
Also called Canakinumab
| Study group | Role | What they receive |
|---|---|---|
| canakinumab | Experimental | Patients will receive a standard dose at an equivalent of 2 mg/kg s.c. of canakinumab (ACZ885) every 8 weeks. Possible dose and/or dosing regimen adjustments that can be administered include: 4 mg/kg s.c. (every 4 to 8 weeks) 6 mg/kg s.c. (every 4 to 8 weeks) 8 mg/kg s.c. (every 4 to 8 weeks) Receives: Biological: ACZ885 |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Percentage of Participants Without Disease Relapse as Determined by the Physician's Global Assessment of Autoinflammatory Disease Activity, Assessment of Skin Disease and Serological Inflammation Markers.
Disease relapse following complete response is defined as inflammation markers: C-Reactive Protein (CRP) and/or Serum Amyloid A (SAA) result > 30 mg/L AND Physician's Global Assessment of Autoinflammatory Disease Activity > minimal or Physician's Global Assessment >= minimal AND Skin Disease Assessment > minimal. Physician's Global Assessment of Autoinflammatory Disease Activity and Skin Disease Assessment (urticarial skin rash) are completed by the investigator using a 5 point rating scale: absent, minimal, mild, moderate and severe.
Measured: Week /80, 104, 128, and 152 (A minimum of 6 months and maximum of 24 months)
Secondary outcomes (4)
Immunogenicity of Canakinumab (ACZ885). Number of Participants With Anti-canakinumab Antibodies
Immunogenicity assessment included determination of anti-canakinumab (ACZ885) antibodies in serum samples using BIAcore system, with detection based on surface plasmon resonance technique.
Measured: minimum of 6 months and maximum of 24 months
Change From Baseline (Core Study Baseline) in C--Reactive Protein (CRP) and Serum Amyloid A (SAA) Concentrations
CRP and SAA were used as serologic 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: Week 0, 80, 104, 128 and 152, last assessment
Frequency Counts of Physician's Global Assessment of Autoinflammatory Disease and Skin Disease
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: minimum of 6 months and maximum of 24 months
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: pre-vaccine dose, Day 28 post-vaccine
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2012 (estimated)
- Study start16 Jan 2012
- Primary completion13 Oct 2015
- Study completion13 Oct 2015
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
- Non-randomised
- Intervention model
- Single group
- 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
- NCT01576367
- Sponsor's protocol ID
- CACZ885D2307E1
- Other IDs
- 2011-005154-57
- Status last verified
- Aug 2018
- First submitted
- 17 Feb 2012
- Last updated
- 11 Sep 2018
- 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 11 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label Extension Study to Assess Efficacy, Safety and Tolerability of Canakinumab and the Efficacy and Safety of Childhood Vaccinations in Patients With Cryopyrin Associated Periodic Syndromes (CAPS)
- ClinicalTrials.gov ID
- NCT01576367
- Acronym / sponsor ID
- CACZ885D2307E1
- 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), 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
- 16 Jan 2012 (actual)
- Primary completion
- 13 Oct 2015 (actual)
- Study completion
- 13 Oct 2015 (actual)
- First posted
- 12 Apr 2012 (estimated)
- Results
- Posted 3 Aug 2016
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 provide long-term safety, efficacy and tolerability of ACZ885 in CAPS patients that completed the CACZ885D2307 study
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| canakinumab | Experimental | Biological: ACZ885Patients will receive a standard dose at an equivalent of 2 mg/kg s.c. of canakinumab (ACZ885) every 8 weeks. Possible dose and/or dosing regimen adjustments that can be administered include: 4 mg/kg s.c. (every 4 to 8 weeks) 6 mg/kg s.c. (every 4 to 8 weeks) 8 mg/kg s.c. (every 4 to 8 weeks) |
Who may qualify
- Ages
- 1 year to 4 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Patients who completed the core CACZ885D2307 study (a patient is defined as having completed the core study if they completed the study up to and including the EOS visit with no major protocol deviations in the core).
- Male and female patients that are ≥ 1 year of age at the time of the roll-over visit.
- Parent or legal guardian written informed consent must be obtained before any assessment in the extension CACZ885D2307E1 study is performed.
Key exclusion criteria (3 listed)
- Patients for who continued treatment in the CACZ885D2307E1 extension study is not considered appropriate by the treating physician.
- Patients who discontinued from the core CACZ885D2307 study
- Other protocol-defined inclusion/exclusion criteria may apply.
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 |
|---|---|---|
| ACZ885Also: Canakinumab | Biological | canakinumab |
Primary outcome
The Percentage of Participants Without Disease Relapse as Determined by the Physician's Global Assessment of Autoinflammatory Disease Activity, Assessment of Skin Disease and Serological Inflammation Markers.
Time frame: Week /80, 104, 128, and 152 (A minimum of 6 months and maximum of 24 months)
Disease relapse following complete response is defined as inflammation markers: C-Reactive Protein (CRP) and/or Serum Amyloid A (SAA) result > 30 mg/L AND Physician's Global Assessment of Autoinflammatory Disease Activity > minimal or Physician's Global Assessment >= minimal AND Skin Disease Assessment > minimal. Physician's Global Assessment of Autoinflammatory Disease Activity and Skin Disease Assessment (urticarial skin rash) are completed by the investigator using a 5 point rating scale: absent, minimal, mild, moderate and severe.
4 secondary outcomes
Immunogenicity of Canakinumab (ACZ885). Number of Participants With Anti-canakinumab Antibodies
Time frame: minimum of 6 months and maximum of 24 months
Change From Baseline (Core Study Baseline) in C--Reactive Protein (CRP) and Serum Amyloid A (SAA) Concentrations
Time frame: Week 0, 80, 104, 128 and 152, last assessment
Frequency Counts of Physician's Global Assessment of Autoinflammatory Disease and Skin Disease
Time frame: minimum of 6 months and maximum of 24 months
Number of Vaccination Cases With Protective Antibody Levels Following Immunization With Inactivated Vaccines
Time frame: pre-vaccine dose, Day 28 post-vaccine
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2018.
- 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.
Related trials for Cryopyrin-associated Periodic Syndromes
RecruitingObservational study
Natural History, Pathogenesis, and Outcome of Autoinflammatory Diseases (NOMID/CAPS, DIRA, CANDLE, SAVI, NLRC4-MAS, Still'S-like Diseases, and Other Undifferentiated Autoinflammatory Diseases)
NOMID, DIRA
RecruitingPhase 1
Repeat PET/CT Imaging in People With CAPS and Anakinra-Induced Amyloidosis Using an Amyloid-Reactive Peptide to Measure Changes in Organ-Specific Amyloid Load
Cryopyrin-Associated Periodic Syndromes, Amyloidosis
RecruitingObservational study
Ilaris NIS in Korea
Hereditary Periodic Fever Syndromes, Cryopyrin-associated Periodic Syndromes (CAPS)
Recruiting
Circadian Rhythm Deregulation in Patients With CAPS
Cryopyrin Associated Periodic Syndrome, Familial Cold Urticaria
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 3 inclusion and 3 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 11 Sep 2018. 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 3 Aug 2016). 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?
The Percentage of Participants Without Disease Relapse as Determined by the Physician's Global Assessment of Autoinflammatory Disease Activity, Assessment of Skin Disease and Serological Inflammation Markers. (time frame: Week /80, 104, 128, and 152 (A minimum of 6 months and maximum of 24 months)). 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 NCT01576367, 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 11 Sep 2018.