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Phase IV Study of Long Term Peg-Intron for Patients Who Have Failed to Respond to Rebetron/Interferon With Advanced Fibrosis and Cirrhosis Secondary to Hepatitis C- The Copilot Trial


Phase 4
18 Years
75 Years
Open (Enrolling)
Both
Hepatitis C Virus, Advanced Fibrosis, Cirrhosis

Thank you

Trial Information

Phase IV Study of Long Term Peg-Intron for Patients Who Have Failed to Respond to Rebetron/Interferon With Advanced Fibrosis and Cirrhosis Secondary to Hepatitis C- The Copilot Trial


We are proposing a randomized trial of Peg-Intron 0.5mcg per kg weekly versus colchicine
0.6mg bid in prior non-responders to Interferon, Rebetron, PegIntron, or PegIntron &
Ribavirin or any third agent such as Pegasys, CellCept, Amantadine with advanced
fibrosis/cirrhosis. The specific aims of this proposal are to evaluate the role of long
term Peg-Intron therapy on the natural history of patients with advanced chronic HCV
infection with a primary focus on prevention of hepatic decompensation, progression of
fibrosis and hepatoma development.

The study design will focus on 3 monthly clinical evaluation for decompensation of liver
function, rigorous clinical screening for development of hepatocellular cancer and liver
biopsies for determination of progression of liver fibrosis every second year.


Inclusion Criteria:



- *Adult male or female, age 18 to 75 years

- HCV RNA positive by PCR

- Previous treatment with at least three months of interferon or interferon /
Ribavirin. Patients should have had no interferon for at least 2 months prior to
enrollment.

1. Non-responders are identified by failure to clear virus by PCR after a
minimum 3-month course of treatment and who have been off treatment for at
least 2 months with a positive PCR for HCV prior to entry into the current
study, 2) Partial responders have a reduction of 1 long in HCV RNA, but the
virus is still detectable, 3) Breakthrough patients have been negative on
treatment, but virus appeared while still on treatment, 4) Relapsers are
defined as negative PCR at some point during treatment, but virus
reoccurred or was detectable by HCV PCR when treatment stopped.

Patients should have had a liver biopsy showing at least Stage 3 disease prior to being
considered for this study. A baseline liver biopsy is necessary for inclusion in the
study. Baseline liver biopsies can be performed within six months of entering the study.

In patients with cirrhosis and endoscopic evidence of portal hypertension, a biopsy within
the last 2 years is acceptable as the baseline biopsy. For patients with established
cirrhosis on liver biopsy and no portal hypertension, a biopsy within 12 months can be
used as the baseline biopsy if it is available for evaluation by the Pathology core. All
these patients will still require liver biopsy at 2 years and 4 years. The decision to
biopsy at 2 and 4 years is also a clinical decision and in the presence of clinical
progression or coagulopathy, or where there may be a risk from liver biopsy, the
Investigator should call the PI, Dr. Afdhal for a waiver of biopsy. Patients with Ishak
Stage 3 and 4 require a biopsy within 6 months of randomization.

- Hemoglobin >= 11 g/dl in males and 10 g/dl in females

- Neutrophil count > 1,500/mm3

- Platelets > 50, 000/mm3

Platelet count: For standard dose of PEG-Intron 0.5mcg/kg platelet count must be greater
than 70,000. Patients with platelet count 50 - 70,000 can start at 0.25mcg/kg for weeks 0
- 4. If platelets fall to less than 30,000, stop treatment. If platelets remain > 50,000
at week 4, PEG-Intron can be increased to 0.5mcg/kg. Patients randomized to Colchicine
with platelets 50,000 - 70,000 can be started at standard dose 0.6mg bid po with standard
dose reduction.

- Prothrombin time <= 3secs prolonged compared to control or an equivalent INR < 1.5

- Total bilirubin < 3gm/dL

- Fasting blood sugar <= 115 mg/dl or within 20% of the upper limit of normal for
non-diabetic patients

- Albumin (> 2.8mg/dl)

- Serum creatinine < 1.4 mg/dL

- TSH within the normal range (Patients with thyroid disease who are well controlled
are eligible if the remainder of the inclusion/exclusion criteria are met)

- HIV negative.

- HBsAg negative

- Childs Pugh score of less than or equal to 7

- Serum positive for anti-hepatitis C antibodies or HCV RNA.

- Alpha-fetoprotein < 100ng/ml with ultrasound negative for focal mass or HCC. For
any patient with an Alpha-fetoprotein >100 ng/ml either a triple phase contrast
CT scan or MRI with gadolinium must show no focal mass or evidence of HCC

- Ultrasound with no evidence of focal mass suggestive of hepatoma (within 6
months of informed consent).

- Documentation that sexually active female patients of childbearing potential are
practicing adequate contraception during the treatment period. A urine
pregnancy test obtained at entry prior to the initiation of treatment must be
negative. Female patients must not be breast-feeding. Documentation that
sexually active male patients are practicing acceptable methods of contraception
during the treatment period.

- Written informed consent specific for this protocol has been obtained prior to
entry.

Exclusion Criteria:

- Any cause of liver disease based on patient history and biopsy (where applicable)
other than chronic hepatitis C including but not limited to:

- Co-infection with hepatitis B or HIV

- Hemochromatosis (confirmed by genetic testing)

- Alpha-1 antitrypsin deficiency

- Wilson's disease

- Renal or liver transplant patients

- Autoimmune hepatitis

- Alcoholic liver disease

- Obesity induced liver disease

- Drug related liver disease

In addition:

- Evidence of decompensated liver disease such as a history or presence of ascites, and
spontaneous encephalopathy. Patients with past bleeding esophageal varices that have
not bled for more than 1 year can be included.

- Hypersensitivity to alpha interferon

- Drug related liver disease

- Hemoglobinopathies (e.g. Thalassaemia, sickle cell disease).

- Patients with clinically significant retinal abnormalities.

- Substance abuse, such as alcohol (ยท> 80 gm/day), I.V. drugs and inhaled drugs. If
the patient has a history of substance abuse, to be considered for inclusion into the
protocol, the patient must have abstained from using the abused substance for at
least 6 months. Patients on methadone will be allowed in the study with no
restrictions as is now standard of care in HCV therapy.

- Patients with a history of organ transplantation will be excluded.

Preexisting psychiatric conditions, especially depression, or a history of severe
psychiatric disorder, such as major psychoses, suicidal ideation and/or suicidal attempt
are excluded. Patients with a history of mild depression may enter the protocol if they
meet the following eligibility criterion and are monitored more intensively.

Mild depression: to include either situational depression of a limited period or
depressive symptoms, which do not significantly interfere with the patient's work or daily
functions.

Any patient with an active manic element to his/her previous symptom complex will be
excluded.

Any known pre-existing medical condition that could interfere with the patient's
participation in and completion of the study such as:

- Pre-existing psychiatric condition, especially severe depression, or a history of
severe psychiatric disorder

- CNS trauma or seizure disorder requiring therapy

- Significant cardiac dysfunction in the previous 6 months e.g. angina, CCF,
hypertension or arrhythmia Patients on treatment are eligible as long as they have
been symptom free for the previous 6 months.

- Poorly controlled diabetes mellitus

- Chronic pulmonary disease (e.g. COAD)

- Immunologically mediated diseases (e.g. inflammatory bowel disease, SLE, ITP,
autoimmune hemolytic anemia, scleroderma, rheumatoid arthritis, severe psoriasis)

- Clinical gout

- Patients with clinically significant retinal abnormalities

- Patients with organ transplants

Any other condition, which in the view of the investigator, would make the patient
unsuitable for enrolment, or could interfere with the patient participating in and
completing the protocol are included as well.

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Outcome Measure:

Determination of the effect of PEG-Intron 0.5mg per kg weekly sc versus colchicine 0.6mg bid daily on:

Principal Investigator

Nezam H Afdhal, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Beth Israel Deaconess Medical Center

Authority:

United States: Food and Drug Administration

Study ID:

2001-P-000002

NCT ID:

NCT00179413

Start Date:

January 2001

Completion Date:

December 2009

Related Keywords:

  • Hepatitis C Virus
  • Advanced Fibrosis
  • Cirrhosis
  • hepatitis C
  • cirrhosis
  • interferon
  • colchicine
  • Fibrosis
  • Hepatitis
  • Hepatitis A
  • Hepatitis C
  • Liver Cirrhosis

Name

Location

Mayo ClinicRochester, Minnesota  55905
Walter Reed Army Medical CenterWashington, District of Columbia  20307-5000
Beth Israel Deaconess Medical CenterBoston, Massachusetts  02215
Roger Williams Medical CenterProvidence, Rhode Island  02908-4735
Dartmouth-Hitchcock Medical CenterLebanon, New Hampshire  03756
Temple University HospitalPhiladelphia, Pennsylvania  19140
Columbia UniversityNew York, New York  10032-3784
University of Colorado Health Sciences CenterDenver, Colorado  80262
Albert Einstein Medical CenterPhiladelphia, Pennsylvania  19141
Lahey ClinicBurlington, Massachusetts  01805
Georgetown University Medical CenterWashington, District of Columbia  20007
Texas Transplant InstituteSan Antonio, Texas  78229
Danbury HospitalDanbury, Connecticut  06810
Fallon ClinicWorcester, Massachusetts  01605
Birmingham Gastroenterology AssociatesBirmingham, Alabama  35209
UAMS Medical CenterLittle Rock, Arkansas  72205
34th Street Community Health CenterBakersfield, California  93301-1645
UC Davis Medical CenterSacramento, California  95817
Kaiser Permanende-GI DepartmentSacramento, California  95825
Gastroenterology AssociatesSan Diego, California  92115
Bruce Stein, MDManchester, Connecticut  06040
Connecticut Gastroenterology ConsultantsNew Haven, Connecticut  06510
Bach and Godofsky Infectious DiseaseBradenton, Florida  34205
Southern Clinical Research ConsultantsHollywood, Florida  33021
Gastroenterology Associates of South FloridaS. Miami, Florida  33143
Digestive Health ServicesDowners Grove, Illinois  60515
Digestive Disease AssociatesBaltimore, Maryland  21229
Hampshire GastroenterologyFlorence, Massachusetts  01062
Wayne State University/Haper HospitalDetroit, Michigan  48601
Gastroenterology Division Veterans Affairs Medical CenterMinneapolis, Minnesota  55417
Minnesota GastroenterologyPlymouth, Minnesota  55446
Gastroenterology AssociatesKansas City, Missouri  64131
VA New Jersey Healthcare SystemEast Orange, New Jersey  07018
Atlantic GastroenterologyEgg Harbor, New Jersey  08234
Florham Park Endoscopy CenterFlorham Park, New Jersey  07932
Northern New Mexico GastroenterologySanta Fe, New Mexico  87505
Dr. Sam Moskowitz, MD, PCForest Hills, New York  11375
Liberty Medical, LLPNew York, New York  10003
Metro MedicalNew York, New York  10011
Peter Varunok, MDPoughkeepsie, New York  12601
Upstate Medical CenterSyracuse, New York  13210
Guthrie Research FoundationSayre, Pennsylvania  18840
University GastroenterologistsProvidence, Rhode Island  02905
Nashville Gastroenterology Specialists IncorporatedNashville, Tennessee  37211
Austin GastroenterologyAustin, Texas  78745
G.I. and Liver AssociatesGranbury, Texas  76048
Digestive Disease CenterSan Antonio, Texas  78205
Health Science CenterSalt Lake City, Utah  84132
Medical Center of WisconsinMilwaukee, Wisconsin  53226