Muckle Wells SyndromePhase 3REMITTERNCT00465985
Efficacy, Safety, and Tolerability of ACZ885 in Patients With Muckle-Wells Syndrome
A Phase 3 study testing ACZ885 in people with Muckle Wells Syndrome, run by Novartis at 12 sites in 6 countries.
Trial summary
This study is designed to provide efficacy and safety data for ACZ885 (a fully human anti-interleukin-1beta (anti-IL-1beta) monoclonal antibody) administered as an injection subcutaneously (s.c.) in patients with Muckle-Wells Syndrome. Read more about this study
- Who is it for?
- Ages 4 to 75 years
- Conditions the study is for
- Muckle Wells Syndrome
- What is being tested?
- ACZ885
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 35 participants
- Where
- 12 sitesin 6 countries
- Study dates
- Apr 2007to Oct 2008
- 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 4 to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Molecular diagnosis of NALP3 mutations and clinical picture resembling Muckle-Wells Syndrome.
- Muckle-Wells Syndrome patients who participated in the CACZ885A2102 study, will have the option to participate in this study upon disease flare
- Muckle-Wells Syndrome patients requiring medical intervention either untreated or treated (i.e. under ACZ885, anakinra, or any other investigational IL-1 blocking therapy).
Who cannot join
- History of being immunocompromised, including a positive HIV at screening test result.
- No 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 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 infections.
- Positive tuberculin skin test at 48 to 72 hours after administration at the screening visit or within 2 months prior to the screening visit, according to national guidelines.
- Other protocol-defined inclusion/exclusion criteria may apply
Trial locations and contacts
12 sites in 6 countries.
12 sites in 6 countries
France5 sites
Novartis Investigative Site
Le Kremlin-Bicêtre
Novartis Investigational Site
Lille
Novartis Investigative Site
Montpellier
Novartis Investigative Site
Nantes
Novartis Investigative Site
Paris
United States3 sites
Novartis Investigative Site
Chicago, Illinois, 60612
Novartis Investigative Site
Madison, Wisconsin, 53792
Novartis Investigative Site
San Francisco, California, 94115
About this study
Official title: A Three-part,Multicenter Study,With a Randomized,Double-blind,Placebo Controlled,Withdrawal Design in Part II to Assess Efficacy,Safety,and Tolerability of ACZ885(Anti-interleukin-1beta Monoclonal Antibody)in Patients With Muckle-Wells Syndrome
This study is designed to provide efficacy and safety data for ACZ885 (a fully human anti-interleukin-1beta (anti-IL-1beta) monoclonal antibody) administered as an injection subcutaneously (s.c.) in patients with Muckle-Wells Syndrome.
Part I is an 8-week open-label, active treatment period to identify ACZ885 responders.
Part II is a double-blind, placebo-controlled period to assess primarily the efficacy of ACZ885 compared to placebo.
Part III is an open-label, active treatment period where patients will receive ACZ885 every 8 weeks after withdrawal or completion of Part II.
- Conditions
- Muckle Wells Syndrome
- Being tested
- ACZ885, Placebo
- Keywords
- Muckle-Wells Syndrome, children, systemic autoinflammatory disease, CIAS-1 gene, NALP-3, ACZ885, human monoclonal anti-human interleukin-1beta (IL-1beta), 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
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Part I, Part II-arm1, & Part III | Experimental | Not described Receives: Drug: ACZ885 |
| Part II - arm 2 | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent of Participants With Disease Flare in Part II (After 24 Weeks of the Double-blind Part)
Determined by the Physician's global assessment of autoinflammatory disease activity, assessment of skin disease and inflammation markers. Data expressed as a percent of participants who had experienced a flare by the end of Part II.
Measured: 32 weeks after study start
Number of Participants Who Experienced a Disease Flare in Part II
Disease flare is determined by the Physician's global assessment of autoinflammatory disease activity, assessment of skin disease and inflammation markers. Disease Flare = the C-reactive protein and/or serum amyloid A (SAA) > 30 mg/L and either a PGA > minimal, or PGA equal to minimal and > minimal SD.
Measured: 32 weeks after study start
Secondary outcomes (7)
Number of Participants With Treatment Response in Part I (After 8 Weeks)
Treatment response was based on Physician's global assessment(PGA) of autoinflammatory disease activity, assessment of skin disease(SD) and serum values of C-reactive protein(CRP) and/or serum amyloid A(SAA). Complete Response (CR):PGA and SD ≤ minimal and normal CRP and/or SAA. Partial Response (PR): a reduction of CRP and/or SAA from baseline (BL) by >30% but not reaching normal values and PGA improvement from BL by at least one category. Disease flare: a CRP and/or SAA > 30 mg/L and either PGA > minimal or PGA = minimal and SD > minimal. Non-responders = no PR by Day 8 or no CR by Day 15.
Measured: 8 weeks after study start
Investigator's Clinical Assessment of Autoinflammatory Disease Activity & Participant's Assessment of Symptoms at End of Part II (After 24 Weeks of the Double-blind Part)
A 5-point scale was used for the Physician's global assessment on autoinflammatory disease activity (absent, minimal, mild, moderate and severe) and for the assessment of the following items:
- skin disease (urticarial skin rash)
- arthralgia
- myalgia
- headache/migraine
- conjunctivitis
- fatigue/malaise
- other symptoms related to autoinflammatory syndrome
- other symptoms not related to autoinflammatory syndrome
Measured: 32 weeks after study start
Change in Inflammation Markers at the End of Part II (C-reactive Protein and/or Serum Amyloid A) (After 24 Weeks of the Double-blind Part) From Week 8.
Measured: Week 8 and Week 32
Pharmacokinetics (CLD (L/d))
Assessed serum clearance of ACZ885.
Measured: 48 weeks after study start
Pharmacodynamics Measured by Interleukin-1β (IL-1β) Concentrations at End of Part I.
Measured: until Week 8
Pharmacodynamics Measured by Interleukin-1β (IL-1β) Concentrations at End of Part II.
Measured: 32 weeks after study start
Pharmacodynamics Measured by Interleukin-1β (IL-1β) Concentrations at End of Part III.
Measured: 48 weeks after study start
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2007 (estimated)
- Study startApr 2007
- Primary completionOct 2008
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 (2)Papers the sponsor has linked to this study.
- Other trials for Muckle Wells SyndromeStudies of the same condition, open and under way.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00465985
- Sponsor's protocol ID
- CACZ885D2304
- Acronym
- REMITTER
- Status last verified
- Jul 2017
- First submitted
- 25 Apr 2007
- Last updated
- 28 Aug 2017
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Kone-Paut I, Lachmann HJ, Kuemmerle-Deschner JB, Hachulla E, Leslie KS, Mouy R, Ferreira A, Lheritier K, Patel N, Preiss R, Hawkins PN; Canakinumab in CAPS Study Group. Sustained remission of symptoms and improved health-related quality of life in patients with cryopyrin-associated periodic syndrome treated with canakinumab: results of a double-blind placebo-controlled randomized withdrawal study. Arthritis Res Ther. 2011;13(6):R202. doi: 10.1186/ar3535. Epub 2011 Dec 9.
PubMed 22152723Lachmann HJ, Kone-Paut I, Kuemmerle-Deschner JB, Leslie KS, Hachulla E, Quartier P, Gitton X, Widmer A, Patel N, Hawkins PN; Canakinumab in CAPS Study Group. Use of canakinumab in the cryopyrin-associated periodic syndrome. N Engl J Med. 2009 Jun 4;360(23):2416-25. doi: 10.1056/NEJMoa0810787.
PubMed 19494217
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Three-part,Multicenter Study,With a Randomized,Double-blind,Placebo Controlled,Withdrawal Design in Part II to Assess Efficacy,Safety,and Tolerability of ACZ885(Anti-interleukin-1beta Monoclonal Antibody)in Patients With Muckle-Wells Syndrome
- ClinicalTrials.gov ID
- NCT00465985
- Acronym / sponsor ID
- REMITTER / CACZ885D2304
- Conditions
- Muckle Wells Syndrome
- Keywords
- Muckle-Wells Syndrome, children, systemic autoinflammatory disease, CIAS-1 gene, NALP-3, ACZ885, human monoclonal anti-human interleukin-1beta (IL-1beta), antibody
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- NovartisIndustry (pharma, biotech, devices)
- Study start
- Apr 2007
- Primary completion
- Oct 2008 (actual)
- First posted
- 27 Apr 2007 (estimated)
- Results
- Posted 11 Feb 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is designed to provide efficacy and safety data for ACZ885 (a fully human anti-interleukin-1beta (anti-IL-1beta) monoclonal antibody) administered as an injection subcutaneously (s.c.) in patients with Muckle-Wells Syndrome.
Part I is an 8-week open-label, active treatment period to identify ACZ885 responders.
Part II is a double-blind, placebo-controlled period to assess primarily the efficacy of ACZ885 compared to placebo.
Part III is an open-label, active treatment period where patients will receive ACZ885 every 8 weeks after withdrawal or completion of Part II.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part I, Part II-arm1, & Part III | Experimental | Drug: ACZ885 |
| Part II - arm 2 | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 4 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Molecular diagnosis of NALP3 mutations and clinical picture resembling Muckle-Wells Syndrome.
- Muckle-Wells Syndrome patients who participated in the CACZ885A2102 study, will have the option to participate in this study upon disease flare
- Muckle-Wells Syndrome patients requiring medical intervention either untreated or treated (i.e. under ACZ885, anakinra, or any other investigational IL-1 blocking therapy).
Key exclusion criteria (6 listed)
- History of being immunocompromised, including a positive HIV at screening test result.
- No 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 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 infections.
- Positive tuberculin skin test at 48 to 72 hours after administration at the screening visit or within 2 months prior to the screening visit, according to national guidelines.
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 | Part I, Part II-arm1, & Part III |
| Placebo | Drug | Part II - arm 2 |
Primary outcome
Percent of Participants With Disease Flare in Part II (After 24 Weeks of the Double-blind Part)
Time frame: 32 weeks after study start
Determined by the Physician's global assessment of autoinflammatory disease activity, assessment of skin disease and inflammation markers. Data expressed as a percent of participants who had experienced a flare by the end of Part II.
Number of Participants Who Experienced a Disease Flare in Part II
Time frame: 32 weeks after study start
Disease flare is determined by the Physician's global assessment of autoinflammatory disease activity, assessment of skin disease and inflammation markers. Disease Flare = the C-reactive protein and/or serum amyloid A (SAA) > 30 mg/L and either a PGA > minimal, or PGA equal to minimal and > minimal SD.
7 secondary outcomes
Number of Participants With Treatment Response in Part I (After 8 Weeks)
Time frame: 8 weeks after study start
Investigator's Clinical Assessment of Autoinflammatory Disease Activity & Participant's Assessment of Symptoms at End of Part II (After 24 Weeks of the Double-blind Part)
Time frame: 32 weeks after study start
Change in Inflammation Markers at the End of Part II (C-reactive Protein and/or Serum Amyloid A) (After 24 Weeks of the Double-blind Part) From Week 8.
Time frame: Week 8 and Week 32
Pharmacokinetics (CLD (L/d))
Time frame: 48 weeks after study start
Pharmacodynamics Measured by Interleukin-1β (IL-1β) Concentrations at End of Part I.
Time frame: until Week 8
Pharmacodynamics Measured by Interleukin-1β (IL-1β) Concentrations at End of Part II.
Time frame: 32 weeks after study start
Pharmacodynamics Measured by Interleukin-1β (IL-1β) Concentrations at End of Part III.
Time frame: 48 weeks after study start
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 22152723Kone-Paut I, Lachmann HJ, Kuemmerle-Deschner JB, Hachulla E, Leslie KS, Mouy R, Ferreira A, Lheritier K, Patel N, Preiss R, Hawkins PN; Canakinumab in CAPS Study Group. Sustained remission of symptoms and improved health-related quality of life in patients with cryopyrin-associated periodic syndrome treated with canakinumab: results of a double-blind placebo-controlled randomized withdrawal study. Arthritis Res Ther. 2011;13(6):R202. doi: 10.1186/ar3535. Epub 2011 Dec 9.
- Derived from this study: PubMed 19494217Lachmann HJ, Kone-Paut I, Kuemmerle-Deschner JB, Leslie KS, Hachulla E, Quartier P, Gitton X, Widmer A, Patel N, Hawkins PN; Canakinumab in CAPS Study Group. Use of canakinumab in the cryopyrin-associated periodic syndrome. N Engl J Med. 2009 Jun 4;360(23):2416-25. doi: 10.1056/NEJMoa0810787.
Related trials for Muckle Wells Syndrome
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
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.
The record lists no contact. Use the official record to reach the sponsor.
12 sites in 6 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 Muckle Wells Syndrome, run by Novartis at 12 sites in 6 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 6 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 28 Aug 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 France, United States, Germany, India, Spain and 1 more country. 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. Some participants in this study may receive a placebo. 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 11 Feb 2011). 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?
Percent of Participants With Disease Flare in Part II (After 24 Weeks of the Double-blind Part) (time frame: 32 weeks after study start). The study lists 2 primary outcomes in all. 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 NCT00465985, which also lists 2 linked publications.
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 28 Aug 2017.