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Oral Administration of Anti-CD3 Monoclonal Antibody in Non-responder Genotype-I Chronic Hepatitis C Subjects

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2011 by Inspira Medical AB.
Recruitment status was  Not yet recruiting
Sponsor:
Collaborator:
NasVax Ltd
Information provided by (Responsible Party):
Inspira Medical AB
ClinicalTrials.gov Identifier:
NCT01459419
First received: October 23, 2011
Last updated: NA
Last verified: October 2011
History: No changes posted
  Purpose

The use of oral aCD3 Monoclonal antibody (MAb) alone in subjects with hepatitis C is justified on the basis of scientific and medical reasons. There are data in multiple animal models that aCD3-alone confers efficacy in models of inflammatory or autoimmune disease and induces regulatory T cells and immune-modulation as desired in clinical studies. These observations are reinforced by data in the Phase 1 clinical study showing that aCD3-alone induced the desired immune-modulation in terms of immunological markers for regulatory T cells and appropriate rises and declines in certain cytokine levels.


Condition Intervention Phase
Chronic Hepatitis C
Drug: anti-CD3 monoclonal antibody
Drug: Sodium Chloride placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase IIa Safety Study of Oral Administration of Anti-CD3 Monoclonal Antibody in Non-responder Genotype-I Chronic Hepatitis C Subjects, a Single-blind, Randomized, Controlled Multi-center Study.

Resource links provided by NLM:


Further study details as provided by Inspira Medical AB:

Primary Outcome Measures:
  • This clinical study is designed to evaluate as Primary Objective the safety of oral administration of the study drug anti-CD3 MAb to non responder genotype I subjects with the chronic Hepatitis C. [ Time Frame: 60 ] [ Designated as safety issue: Yes ]
    The safety and tolerability of oral administration of the study drug cocktail will be evaluated at Days 7, 14, 21 and 30 by physical examinations and thorough medical history and laboratory evaluations as described below and by the subject through his/her diary entries. In addition, subjects will be assessed for safety at Day 60


Secondary Outcome Measures:
  • Decrease in the concentration of HCV [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    30 days

  • Liver function test [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    Changes in ALT will be used to evaluate effect on liver


Estimated Enrollment: 36
Study Start Date: November 2011
Estimated Study Completion Date: October 2013
Estimated Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: anti-CD3 monoclonal antibody
Oral anti-CD3 MAb will be administered at a dosage level of 0.2 or 1.0 or 5.0 mg per day for 30 days. Up to 9 subjects will be treated at each dosage level
Drug: anti-CD3 monoclonal antibody
Oral anti-CD3 MAb will be administered at a dosage level of 0.2 or 1.0 or 5.0 mg per day for 30 days. One 20mg tablet of Omeprazole (a proton pump inhibitor) will be taken concomitantly orally
Placebo Comparator: Sodium chloride
Up to 9 subjects will receive placebo. Subjects will receive the drug in a similar manner as as the treatment group
Drug: Sodium Chloride placebo
Sodium chloride will be administered orally every day for 30 days. Up to 9 subjects will be treated at each dosage level. One 20mg tablet of Omeprazole (a proton pump inhibitor) will be taken concomitantly orally

Detailed Description:

Oral aCD3 MAb will be administered at a dosage level of 0.2 or 1.0 or 5.0 mg per day for 30 days. Up of 9 subjects will be treated at each dosage level, and up to 9 subjects will receive placebo buffered in normal saline that is used as diluents for the MAb. One 20mg tablet of Omeprazole (a proton pump inhibitor) will be taken orally as part of the study drug cocktail in order to neutralize stomach pH for enhancing stability of the MAb. During the treatment period, subjects will ingest the study drug/s every day for 30 days, and will be followed for clinical and laboratory effects. Subjects will be followed up to Day 60 (30 days after termination of treatment)

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • Subjects who have completed the informed consent process culminating with written informed consent by the subject.
  • Men and women age 18 to 65 years (inclusive).
  • Diagnosis of chronic active HCV infection was based on liver biopsy (within 3 years of initiation of study),
  • Patients who failed treatment with Interferon or Peg-Interferon and Ribavirin (<2-log change in HCV level during the 12 weeks of treatment)
  • HCV RNA in blood for at Screening Visit, ≥600 copies/mL
  • Abstinence from any alternative medications or vitamin-D-containing supplements for three months prior to initiation of therapy was stipulated.
  • Compensated liver disease with the following maximum hematologic, biochemical and serologic criteria at the Screening visit (WNL=within normal limits) Hemoglobin ≥ 12 g/dl for women and ≥ 13 g/dl for men, WBC > 3000/mm3, Platelets > 100,000/mm3, Direct bilirubin - WNL. Indirect bilirubin - WNL, Albumin - WNL, Serum Creatinine - WNL. Child-Pugh score ≤ 6.
  • Fasting glucose should be 70 -140 mg/dl, results between 116-140 require HbA1c < 7.5%
  • Antinuclear antibodies (ANA) up to +1
  • HCV Genotype I patients

Exclusion Criteria:

  • Subjects who have undergone surgery within the last 3 months.
  • Subjects who have had a prior gastrointestinal surgery.
  • Subjects with organ transplants other than cornea or hair transplant.
  • Subjects with Inflammatory Bowel Disease, malabsorption, and symptoms of diarrhea.
  • Subjects with a clinically significant (during last 3 months) infectious, immune-mediated or malignant disease.
  • Subjects who are receiving an elemental diet or parenteral nutrition.
  • Subjects who have been treated with any type of immune modulatory drug including systemic steroids or NSAID within the last 4 weeks.
  • Subjects who have received either methotrexate or cyclosporine or anti-TNF (infliximab, Remicade) or anti-integrin (namixilab) at any time or who have participated in any other clinical trial within the last 3 months.
  • Subjects with a history of coagulopathy.
  • ALT level more than 10 times the normal limit.
  • Women with childbearing potential unless using adequate contraception (either IUD, oral or Depo-provera contraceptive, or barrier plus spermicide); pregnant or breastfeeding mothers.
  • Subjects who will be unavailable for the duration of the trial, who are unlikely to be compliant with the protocol, or who are felt to be unsuitable by the Investigator for any other reason.
  • Subjects who are HIV-positive.
  • Subjects who are positive for anti-HBcAg
  • Subjects with active CMV infection.
  • Subjects with autoimmune hepatitis
  • Subjects with IgG anti-cardiolipin antibody >16 IU.
  • Any prior exposure to anti-CD3 MAb.
  • Known sensitivity to any ingredients in the study drug
  • Any know autoimmune disease except for the studied disorders
  • Subjects with excess alcohol use (> 30 g/day)
  • Subjects with drug addiction based on the physician's judgment
  • Subjects with TSH >6 mIU/L
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01459419

Contacts
Contact: Waldemar Halota, Prof. +48 52 325 56 kikchzak@cm.umk.pl

Locations
Austria
Univ.Klinik für Innere Medizin IV Not yet recruiting
Wien, Austria, A-1090
Contact: Peter Ferenci, Prof.Dr.    +43 1 40400 4741    peter.ferenci@meduniwien.ac.at   
Principal Investigator: Peter Ferenci, Prof.Dr.         
Poland
Katedra i Klinika Chorób Zakaźnych i Hepatologii Wojewódzki Szpital Obserwacyjno - Zakaźny im. Tadeusza Browicza Not yet recruiting
Bydgoszcz, Poland, 85 030
Contact: Waldemar Halota, Prof    >+48 52 325 5605    kikchzak@cm.umk.pl   
Principal Investigator: Waldemar Halota, Prof         
Sponsors and Collaborators
Inspira Medical AB
NasVax Ltd
Investigators
Principal Investigator: Waldemar Halota, Prof Katedra i Klinika Chorób Zakaźnych i Hepatologii Wojewódzki Szpital Obserwacyjno - Zakaźny im. Tadeusza Browicza
  More Information

No publications provided

Responsible Party: Inspira Medical AB
ClinicalTrials.gov Identifier: NCT01459419     History of Changes
Other Study ID Numbers: ISM-10-06
Study First Received: October 23, 2011
Last Updated: October 23, 2011
Health Authority: Austria: Agency for Health and Food Safety
Poland: Ministry of Health

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Hepatitis, Chronic
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Antibodies
Antibodies, Monoclonal
Immunoglobulins
Proton Pump Inhibitors
Enzyme Inhibitors
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 19, 2014