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

NCT ID: NCT00035334

Last Updated: 2006-02-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-10-31
• Study Completion Date: 2004-12-31

Brief 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.

Detailed 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.

Conditions

Secondary (AA) Amyloidosis; Rheumatoid Arthritis; Nephrotic Syndrome; Familial Mediterranean Syndrome; Kidney Diseases; Gastrointestinal Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Interventions

NC-503 (Anti-amyloidotic (AA) Agent)

Intervention Type: DRUG

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

FDA Office of Orphan Products Development

FED

Sponsor Role: collaborator

Bellus Health Inc. - a GSK company

INDUSTRY

Sponsor Role: lead

Locations

Indiana University School of Medicine, Department of Pathology and Laboratory Medicine,

Indianapolis, Indiana, United States

Boston Medical Center, Renal Division

Boston, Massachusetts, United States

Mayo Clinic

Rochester, Minnesota, United States

Mount Sinai Medical Center

New York, New York, United States

Rheumatism Foundation Hospital

Heinola, , Finland

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, , France

Bnai Zion Medical Center

Haifa, , Israel

Heller Institute of Medical Research, Sheba Medical Center

Tel Litwinsky, , Israel

Italian Group for Systemic Amyloidosis, Biotechnology Research Laboratories, IRCCS Policlinico San Matteo, Internal Medicine and Medical Oncology

Pavia, , Italy

Vilnius University Hospital

Vilnius, , Lithuania

University Hospital Groningen, Department of Medicine, Division of Rheumatology

Groningen, , Netherlands

Instytut Reumatologiczny

Warsaw, , Poland

Okregowy Szpital Kolejowy, Zaklad Reumatologii

Wroclaw, , Poland

Institute of Rheumatology RAMS

Moscow, , Russia

Regional Hospital No. 1

Yekaterinburg, , Russia

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, , Spain

Cerrehpasa Tip Fakultesi

Askaray, Istanbul, Turkey, , Turkey (Türkiye)

Istanbul Faculty of Medicine, Department of Internal Medicine, Division of Rheumatology

Istanbul, , Turkey (Türkiye)

Marmara University Medical School Hospital, Department of Rheumatology

Uskudar, Altunizade, Istanbul, , Turkey (Türkiye)

Royal Free and University College Medical School, Department of Medicine, National Amyloidosis Centre

London, , United Kingdom

Gartnavel General Hospital

Scotland, , United Kingdom

Countries

United States; Finland; France; Israel; Italy; Lithuania; Netherlands; Poland; Russia; Spain; Turkey (Türkiye); United Kingdom

References

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)

Reference Type: BACKGROUND

Dember LM, Hawkins PN, Hazenberg BP, Gorevic PD, Merlini G, Butrimiene I, Livneh A, Lesnyak O, Puechal X, Lachmann HJ, Obici L, Balshaw R, Garceau D, Hauck W, Skinner M; Eprodisate for AA Amyloidosis Trial Group. Eprodisate for the treatment of renal disease in AA amyloidosis. N Engl J Med. 2007 Jun 7;356(23):2349-60. doi: 10.1056/NEJMoa065644.

Reference Type: DERIVED

PMID: 17554116 (View on PubMed)

Other Identifiers

CL-503004

Identifier Type: -

Identifier Source: org_study_id

NCT00017667

Identifier Type: -

Identifier Source: nct_alias