NALP3 MutationPhase 2NCT00487708
Safety, Efficacy, Pharmacokinetics, Pharmacodynamics of ACZ885 in Patients With NALP3 Mutations and Clinical Symptoms
A Phase 2 study testing canakinumab in people with NALP3 Mutation, run by Novartis Pharmaceuticals at 10 sites in 5 countries.
Trial summary
This study will investigate the clinical efficacy, safety, pharmacokinetics (PK) and pharmacodynamics (PD) of ACZ885, administered intravenously and subcutaneously to patients with NALP3 mutations whose clinical symptoms are either untreated or insufficiently treated and require medical intervention. Read more about this study
- Who is it for?
- Ages 4 to 75 years
- Conditions the study is for
- NALP3 Mutation
- What is being tested?
- canakinumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 10 sitesin 5 countries
- Study dates
- Jan 2005to Jul 2008
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- Patients aged 4 to 75 years (inclusive)
- Body weight ≥ 12 kg and < 100 kg.
- Females of child-bearing potential must have a negative pregnancy test. Additional birth control details to be provided at screening.
- Documented molecular diagnosis of NALP3 mutations and clinical symptoms that are either untreated or insufficiently treated and require medical intervention.
- Patients under anakinra therapy or any other IL-1 blocking therapy, whose clinical symptoms improved under treatment and are willing to discontinue that therapy until a relapse becomes evident.
- Patients with a very severe characteristics requiring oral prednisone are eligible if the dose is stable (≤ 0.4 mg/kg/day or ≤ 20 mg/day, whichever is lower) for at least 1 week prior to the screening visit. Steroid therapy may be tapered during treatment with ACZ885 at the discretion of the investigator.
- Parents' or legal guardian's written informed consent (patient's informed consent for ≥ 18 years of age) and child's assent, if appropriate, are required prior to study participation.
Who cannot join
- Participation in any clinical trial investigation (except trials with anakinra) within 4 weeks prior to dosing or longer per local regulation
- Antiinflammatory therapy with colchicine, chlorambucil, dapsone, azathioprine, mycophenolate mofetil, within 3 weeks prior to dosing. Therapeutic antibodies (e.g. anti-TNF-alpha antibodies) must be discontinued at least 60 days before dosing.
- Donation or loss of 400 mL or more of blood within 8 weeks prior to dosing.
- A past personal or close family medical history of clinically significant ECG abnormalities or prolonged QT-interval syndrome.
- History of
- Immunocompromise, including a positive HIV result.
Show all 13Show fewer
- Positive Hepatitis B surface antigen or Hepatitis C test result.
- Drug or alcohol abuse within the 12 months prior to dosing.
- Tuberculosis.
- Renal transplant.
- Evidence of lymphoma.
- Active medical condition preventing participation in the study such as infection, poorly controlled diabetes etc.
- 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.
Trial locations and contacts
10 sites in 5 countries.
10 sites in 5 countries
Germany6 sites
Novartis Investigator Site
Berlin
Novartis Investigator Site
Dresden
Novartis Investigator Site
Heidelberg
Novartis Investigator Site
Marburg
Novartis investigative site
Nuremberg
Novartis Investigator Site
Tübingen
About this study
Official title: An Open-Label, Phase II Dose Titration Study of ACZ885 (Human Anti-IL-1β Monoclonal Antibody) to Assess the Clinical Efficacy, Safety, Pharmacokinetics and Pharmacodynamics in Patients With NALP3 Mutations
This study will investigate the clinical efficacy, safety, pharmacokinetics (PK) and pharmacodynamics (PD) of ACZ885, administered intravenously and subcutaneously to patients with NALP3 mutations whose clinical symptoms are either untreated or insufficiently treated and require medical intervention.
- Conditions
- NALP3 Mutation
- Being tested
- canakinumab
- Keywords
- ACZ885, NALP3 mutations, Interleukin-1beta, Muckle-Wells Syndrome
- Medical subject headings
- Cryopyrin-Associated Periodic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
canakinumabDrug
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | ACZ885 Receives: Drug: canakinumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response to treatment and time to relapse after ACZ885 administration according to monthly investigator's clinical assessments, laboratory monitoring, and patient diaries.
Measured: Every month
Secondary outcomes (1)
Assessment of safety,tolerability and immunogenicity of ACZ885 at each clinical visit. Evaluation of ACZ885 PK and PD at each clinical visit Evaluate efficacy towards hearing loss(every 4 months),kidney function (every 4 months),neurological symptoms
Measured: Every month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jun 2007 (estimated)
- Study startJan 2005
- Primary completionJul 2008
- Study completionJul 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for NALP3 MutationStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Novartis, Principal investigator, Investigative site
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00487708
- Sponsor's protocol ID
- CACZ885A2102
- Status last verified
- Feb 2009
- First submitted
- 18 Jun 2007
- Last updated
- 17 Feb 2009
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Kuemmerle-Deschner JB, Ramos E, Blank N, Roesler J, Felix SD, Jung T, Stricker K, Chakraborty A, Tannenbaum S, Wright AM, Rordorf C. Canakinumab (ACZ885, a fully human IgG1 anti-IL-1beta mAb) induces sustained remission in pediatric patients with cryopyrin-associated periodic syndrome (CAPS). Arthritis Res Ther. 2011 Feb 28;13(1):R34. doi: 10.1186/ar3266.
PubMed 21356079
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Phase II Dose Titration Study of ACZ885 (Human Anti-IL-1β Monoclonal Antibody) to Assess the Clinical Efficacy, Safety, Pharmacokinetics and Pharmacodynamics in Patients With NALP3 Mutations
- ClinicalTrials.gov ID
- NCT00487708
- Acronym / sponsor ID
- CACZ885A2102
- Conditions
- NALP3 Mutation
- Keywords
- ACZ885, NALP3 mutations, Interleukin-1beta, Muckle-Wells Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Jan 2005
- Primary completion
- Jul 2008 (actual)
- Study completion
- Jul 2008 (actual)
- First posted
- 19 Jun 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will investigate the clinical efficacy, safety, pharmacokinetics (PK) and pharmacodynamics (PD) of ACZ885, administered intravenously and subcutaneously to patients with NALP3 mutations whose clinical symptoms are either untreated or insufficiently treated and require medical intervention.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: canakinumabACZ885 |
Who may qualify
- Ages
- 4 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Patients aged 4 to 75 years (inclusive)
- Body weight ≥ 12 kg and < 100 kg.
- Females of child-bearing potential must have a negative pregnancy test. Additional birth control details to be provided at screening.
- Documented molecular diagnosis of NALP3 mutations and clinical symptoms that are either untreated or insufficiently treated and require medical intervention.
- Patients under anakinra therapy or any other IL-1 blocking therapy, whose clinical symptoms improved under treatment and are willing to discontinue that therapy until a relapse becomes evident.
Key exclusion criteria (13 listed)
- Participation in any clinical trial investigation (except trials with anakinra) within 4 weeks prior to dosing or longer per local regulation
- Antiinflammatory therapy with colchicine, chlorambucil, dapsone, azathioprine, mycophenolate mofetil, within 3 weeks prior to dosing. Therapeutic antibodies (e.g. anti-TNF-alpha antibodies) must be discontinued at least 60 days before dosing.
- Donation or loss of 400 mL or more of blood within 8 weeks prior to dosing.
- A past personal or close family medical history of clinically significant ECG abnormalities or prolonged QT-interval syndrome.
- History of
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 |
|---|---|---|
| canakinumab | Drug | 1 |
Primary outcome
Response to treatment and time to relapse after ACZ885 administration according to monthly investigator's clinical assessments, laboratory monitoring, and patient diaries.
Time frame: Every month
1 secondary outcome
Assessment of safety,tolerability and immunogenicity of ACZ885 at each clinical visit. Evaluation of ACZ885 PK and PD at each clinical visit Evaluate efficacy towards hearing loss(every 4 months),kidney function (every 4 months),neurological symptoms
Time frame: Every month
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2009.
- Derived from this study: PubMed 21356079Kuemmerle-Deschner JB, Ramos E, Blank N, Roesler J, Felix SD, Jung T, Stricker K, Chakraborty A, Tannenbaum S, Wright AM, Rordorf C. Canakinumab (ACZ885, a fully human IgG1 anti-IL-1beta mAb) induces sustained remission in pediatric patients with cryopyrin-associated periodic syndrome (CAPS). Arthritis Res Ther. 2011 Feb 28;13(1):R34. doi: 10.1186/ar3266.
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 principal investigator
Investigative site
10 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing canakinumab in people with NALP3 Mutation, run by Novartis Pharmaceuticals at 10 sites in 5 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 7 inclusion and 13 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 17 Feb 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Germany, France, India, Spain, United Kingdom. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Response to treatment and time to relapse after ACZ885 administration according to monthly investigator's clinical assessments, laboratory monitoring, and patient diaries. (time frame: Every month). 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 NCT00487708, 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 17 Feb 2009.