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.

Condition	Treatment or Intervention	Phase
Secondary (AA) Amyloidosis Rheumatoid Arthritis Nephrotic Syndrome Familial Mediterranean Syndrome Kidney Diseases Gastrointestinal Diseases	Drug: NC-503 (Anti-amyloidotic (AA) Agent)	Phase II Phase III

Further Study Details: 

Expected Total Enrollment:  150

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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

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.

Indiana
      Indiana University School of Medicine, Department of Pathology and Laboratory Medicine,, Indianapolis,  Indiana,  46202,  United States
Massachusetts
      Boston Medical Center, Renal Division, Boston,  Massachusetts,  02118,  United States
Minnesota
      Mayo Clinic, Rochester,  Minnesota,  55905,  United States
New York
      Mount Sinai Medical Center, New York,  New York,  10029,  United States
Finland
      Rheumatism Foundation Hospital, Heinola,  FIN-18120,  Finland
France
      Hôpital Claude Huriez, Service de médecine Interne, Clinique Médicale A, Lille,  CEDEX 59037,  France
      Centre Hospitalier du Mans, Service de Rhumatologie, Le Mans,  CEDEX 1,  France
      Hôpital Cochin, Centre de Recherche et d'Explorations Fonctionnelles, Paris,  75679 CEDEX 14,  France
Israel
      Bnai Zion Medical Center, Haifa,  31048,  Israel
      Heller Institute of Medical Research, Sheba Medical Center, Tel Hashomer,  52621,  Israel
Italy
      Italian Group for Systemic Amyloidosis, Biotechnology Research Laboratories, IRCCS Policlinico San Matteo, Internal Medicine and Medical Oncology, Pavia,  27100,  Italy
Lithuania
      Vilnius University Hospital, Vilnius,  2001,  Lithuania
Netherlands
      University Hospital Groningen, Department of Medicine, Division of Rheumatology, Groningen,  9700 RB,  Netherlands
Poland
      Instytut Reumatologiczny, Warszawa,  02-632,  Poland
      Okregowy Szpital Kolejowy, Zaklad Reumatologii, Wroclaw,  53-137,  Poland
Russian Federation
      Regional Hospital No. 1, Yekaterinburg,  320102,  Russian Federation
      Institute of Rheumatology RAMS, Moscow,  115522,  Russian Federation
Spain
      Hospital Clinic I Provincial de Barcelona, Jefe del Departamento de Reumatologia, Barcelona,  08036,  Spain
      Hospital Universitario Germans Trias I Pujol, Servicio de Reumatologia, Badalona,  08916,  Spain
      Ciutad Sanitària y Universitària de Bellvitge, Servicio de Reumatologia, Hospitalet de Llobregat, Llobregat,  08907,  Spain
      Hospital Clinico San Carlos de Madrid, Servicio de Reumatologia, Madrid,  28040,  Spain
Turkey
      Istanbul Faculty of Medicine, Department of Internal Medicine, Division of Rheumatology, Istanbul,  34390 CAPA,  Turkey
      Marmara University Medical School Hospital, Department of Rheumatology, Uskudar, Altunizade, Istanbul,  81190,  Turkey
      Cerrehpasa Tip Fakultesi, Askaray, Istanbul, Turkey,  Turkey
United Kingdom
      Gartnavel General Hospital, Scotland,  G12 0YN,  United Kingdom
      Royal Free and University College Medical School, Department of Medicine, National Amyloidosis Centre, London,  NW3 2PF,  United Kingdom

Study ID Numbers:  CL-503004
Record last reviewed:  February 2003
Last Updated:  October 13, 2004
Record first received:  May 2, 2002
ClinicalTrials.gov Identifier:  NCT00035334
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08