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

Sponsor

Bellus Health Inc (Industry)

Overall Status

Completed

CT.gov ID

NCT00035334

Collaborator

FDA Office of Orphan Products Development (U.S. Fed)

150

Enrollment

Locations

Duration (Months)

5.8

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Secondary (AA) Amyloidosis Rheumatoid Arthritis Nephrotic Syndrome Familial Mediterranean Syndrome Kidney Diseases Gastrointestinal Diseases	Drug: NC-503 (Anti-amyloidotic (AA) Agent)	Phase 2/Phase 3

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.

Study Design

Study Type:

Interventional

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Oct 1, 2001

Study Completion Date :

Dec 1, 2004

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

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