Study of the Safety and Efficacy of NC-503 in Secondary (AA) Amyloidosis

Rheumatoid Arthritis Clinical Trial

Official title:

A Phase II/III Study of the Safety and Efficacy of NC-503 in Patients Suffering From Secondary (AA) Amyloidosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00035334
• Other study ID #: CL-503004
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: May 2, 2002
• Last updated: February 13, 2006
• Start date: October 2001
• Est. completion date: December 2004

Study information

• Verified date: February 2006
• Source: Bellus Health Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The main objective of this study is to evaluate the safety and efficacy of NC-503 compared to placebo in patients with secondary (AA) amyloidosis using a composite assessment of clinical improvement/worsening of both renal and gastrointestinal functions.

Description:

AA amyloidosis is associated with chronic inflammatory conditions (rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease), chronic infection (tuberculosis, osteomyelitis), and Familial Mediterranean Fever. Rheumatoid arthritis is the major cause of AA amyloidosis in Western Europe and North America. The most common clinical feature of AA amyloidosis is renal dysfunction manifested as nephrotic-range proteinuria or renal insufficiency at the time of diagnosis. End-stage renal failure is the cause of death in 40-60% of cases. Gastrointestinal involvement is also frequent and is usually manifested as chronic diarrhea, body weight loss and malabsorption. Enlargement of the liver and spleen may also occur in some patients. The median survival time from diagnosis varies from 2 to 8 years depending on the stage of the disease at time of diagnosis. The goal of the current therapy in AA amyloidosis is the control of the associated disease. However, the current approaches for the treatment of AA amyloidosis are unspecific, toxic, invasive, and not sufficiently effective in many cases. NC-503 was specifically designed to compete with the naturally occurring sulfated GAGs for the binding to amyloidogenic precursor proteins, and to inhibit amyloid deposition into tissues. The proposed therapy with NC-503 is based on the prevention of the amyloid fibril formation. The objective of this clinical phase II/III study is to determine the efficacy and safety of NC-503 compared to a placebo in patients suffering from secondary (AA) amyloidosis by the assessment of clinical improvement/ worsening of both renal and gastrointestinal functions.

Other known NCT identifiers

• NCT00017667

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: December 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

PROTOCOL INCLUSION CRITERIA

• Patients must be 18 years of age or older.

• Males and females. If women of childbearing potential (i.e., not surgically sterilized or post-menopausal greater than one year) the patient must be using effective birth control.

• Diagnosis of AA amyloidosis demonstrated by positive biopsy (Congo red staining) and immunohistochemistry or immunoelectron microscopy at screening visit. Tissue from previous biopsy can be used for confirmation of diagnosis, if available.

• Persistent proteinuria defined as urinary protein excretion ? 1g/24h in two distinct 24-h urine collections at least 1 week apart within 3 months prior to study entry (baseline, Month 0 visit) without evidence of urinary tract infection or overt heart failure (NYHA class III or more); OR creatinine clearance ? 60 mL/min in two distinct measures at least 1 week apart within 3 months prior to study entry (baseline, Month 0 visit).

• Creatinine clearance ? 20 mL/min AND serum creatinine ? 3 mg/dl within 3 months prior to study entry (baseline, Month 0 visit).

• Written informed consent.

PROTOCOL EXCLUSION CRITERIA

• Evidence or suspicion of renal or renovascular diseases other than renal AA amyloidosis.

• Presence of diabetes mellitus (Type I and II).

• Evidence of a cause of potentially reversible reduced renal function, such as accelerated hypertension or drug nephrotoxicity.

• AST, ALT, or ALP > 5 times the upper limit of normal, or total bilirubin 50% above upper limits of normal.

• Presence of any other clinically significant diseases that could interfere with the interpretation of study results or compromise patient safety or any conditions that could reduce life expectancy to less than two years.

• Use of an investigational drug within thirty days prior to the screening visit.

• Active alcohol and/or drug abuse.

• Initiation of or any changes in ACE inhibitor therapy within 3 months prior to the screening visit.

• Initiation of or any changes in cytotoxic agents/colchicine therapy within 3 months prior to the screening visit.

• Inability to provide legal consent.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Amyloidosis
• Arthritis, Rheumatoid
• Digestive System Diseases
• Familial Mediterranean Syndrome
• Gastrointestinal Diseases
• Kidney Diseases
• Neoplasm Metastasis
• Nephrosis
• Nephrotic Syndrome
• Rheumatoid Arthritis
• Secondary (AA) Amyloidosis
• Syndrome

Intervention

Drug:
• NC-503 (Anti-amyloidotic (AA) Agent)

Locations

Country	Name	City	State
Finland	Rheumatism Foundation Hospital	Heinola
France	Centre Hospitalier du Mans, Service de Rhumatologie	Le Mans
France	Hôpital Claude Huriez, Service de médecine Interne, Clinique Médicale A	Lille
France	Hôpital Cochin, Centre de Recherche et d'Explorations Fonctionnelles	Paris
Israel	Bnai Zion Medical Center	Haifa
Israel	Heller Institute of Medical Research, Sheba Medical Center	Tel Hashomer
Italy	Italian Group for Systemic Amyloidosis, Biotechnology Research Laboratories, IRCCS Policlinico San Matteo, Internal Medicine and Medical Oncology	Pavia
Lithuania	Vilnius University Hospital	Vilnius
Netherlands	University Hospital Groningen, Department of Medicine, Division of Rheumatology	Groningen
Poland	Instytut Reumatologiczny	Warszawa
Poland	Okregowy Szpital Kolejowy, Zaklad Reumatologii	Wroclaw
Russian Federation	Institute of Rheumatology RAMS	Moscow
Russian Federation	Regional Hospital No. 1	Yekaterinburg
Spain	Hospital Universitario Germans Trias I Pujol, Servicio de Reumatologia	Badalona
Spain	Hospital Clinic I Provincial de Barcelona, Jefe del Departamento de Reumatologia	Barcelona
Spain	Ciutad Sanitària y Universitària de Bellvitge, Servicio de Reumatologia, Hospitalet de Llobregat	Llobregat
Spain	Hospital Clinico San Carlos de Madrid, Servicio de Reumatologia	Madrid
Turkey	Cerrehpasa Tip Fakultesi	Askaray, Istanbul, Turkey
Turkey	Istanbul Faculty of Medicine, Department of Internal Medicine, Division of Rheumatology	Istanbul
Turkey	Marmara University Medical School Hospital, Department of Rheumatology	Uskudar, Altunizade, Istanbul
United Kingdom	Royal Free and University College Medical School, Department of Medicine, National Amyloidosis Centre	London
United Kingdom	Gartnavel General Hospital	Scotland
United States	Boston Medical Center, Renal Division	Boston	Massachusetts
United States	Indiana University School of Medicine, Department of Pathology and Laboratory Medicine,	Indianapolis	Indiana
United States	Mount Sinai Medical Center	New York	New York
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Bellus Health Inc	FDA Office of Orphan Products Development

Countries where clinical trial is conducted

United States,  Finland,  France,  Israel,  Italy,  Lithuania,  Netherlands,  Poland,  Russian Federation,  Spain,  Turkey,  United Kingdom, 

References & Publications (1)

Safety, Tolerability and Pharmacokinetic Profile of FibrillexTM (Anti-AA Amyloid Agent) in Healthy and Renal Impaired Subjects. Garceau D., Gurbindo C., Laurin J. Neurochem Inc. Reference: Proceedings from the IXth International Symposium on Amyloidosis , 2001 (Budapest, Hungary)