An open-label, phase II dose titration study of ACZ885 (human anti-IL-1beta monoclonal antibody) to assess the clinical efficacy, safety, pharmacokinetics and pharmacodynamics in patients with NALP3 mutations - CACZ885A2102

• Conditions: Muckle-Wells Syndrome: rare hereditary, autosomal dominant, systemic inflammatory disease, characterized by recurrent episodes of fever, arthralgia, myalgia, urticarial rash, and conjunctivitis. Laboratory findings show an elevation of acute phase proteins such as CRP and SAA, a high ESR, together with leukocytosis, and hypergammaglobulinemia. Severe long term complications include progressive sensorineural deafness, and in systemic AA amyloidosis.

• Registration Number: EUCTR2004-002980-26-GB
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2005-02-23
• Last Update Posted: 2 February 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

1. Male and female patients aged 4 to 75 years (inclusive) at the time of the screening visit, having passed screening examinations.

2. Female subjects of child-bearing potential may participate if they have a negative pregnancy test at screening and prior to dosing, and are willing to use, if adequate for age, an effective method of contraception (e.g. birth control pills, abstinence, double-barrier contraception, etc.) during the study (from the date of screening) and for at least 3 months following the last dose.

3. Molecular diagnosis of NALP3 mutations and clinical picture resembling MWS/ FCAS/ NOMID requiring medical intervention being either untreated or insufficiently treated.

4. Molecular diagnosis of NALP3 mutations and documented history of a clinical picture resembling MWS/FCAS/NOMID. Patients under anakinra therapy or any other IL-1 blocking therapy being in complete remission and willing to discontinue anakinra/IL-1 blocking therapy until a clinical picture of the disease (relapse) becomes evident.

5. Patients with a very severe phenotype requiring stable doses of oral prednisone (= 0.4 mg/kg/day or = 20 mg/day, whichever is lower) for at least one week prior to the screening visit. Steroid therapy may be tapered during treatment with ACZ885 at the discretion of the investigator.

6. Body weight = 12 kg and < 100 kg.

7. 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.

8. Able to communicate well with the investigator and comply with the requirements of the study.

9. Smokers may participate in the study.

10. Negative tuberculin skin test reaction (PPD 5 tuberculin units or as according to local standard practice) (< 5 mm induration) at 48 to 72 hours after administration at the screening visit or within 2 months prior to the screening visit, according to national guidelines. Patients who have a positive PPD skin test with a documentation of BCG vaccination, who are at low environmental risk for tuberculosis (TB) infection or reactivation, and have a negative chest X-ray can be included. A positive PPD sample will be defined using the MMWR 2000 guidance, summarized as criteria for tuberculin positivity by risk group.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Participation in any clinical investigation within 4 weeks prior to dosing or longer if required by local regulation with the exception of trials with anakinra.

2. Antiinflammatory therapy with colchicine, chlorambucil, dapsone, azathioprine, mycophenolate mofetil, within 3 weeks prior to dosing. In case patients have been treated with therapeutic antibodies (e.g. anti-TNF-alpha antibodies), discontinuation of this therapy is required at least 60 days before dosing.

3. Donation or loss of 400 mL or more of blood within 8 weeks prior to dosing.

4. A past medical history of clinically significant ECG abnormalities or a family history of a prolonged QT-interval syndrome.

5. History of immunocompromise, including a positive HIV (ELISA and Western blot) test result.

6. A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result.

7. History of drug or alcohol abuse within the 12 months prior to dosing.

8. No active medical condition such as infection, poorly controlled diabetes etc.

9. No history of tuberculosis.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified