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

Primary Purpose

Chronic Hepatitis C

Status

Unknown status

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

anti-CD3 monoclonal antibody

Sodium Chloride placebo

About this trial

This is an interventional treatment trial for Chronic Hepatitis C

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Univ.Klinik für Innere Medizin IV
Katedra i Klinika Chorób Zakaźnych i Hepatologii Wojewódzki Szpital Obserwacyjno - Zakaźny im. Tadeusza Browicza

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

anti-CD3 monoclonal antibody

Sodium chloride

Arm Description

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

Up to 9 subjects will receive placebo. Subjects will receive the drug in a similar manner as as the treatment group

Outcomes

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.

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

30 days

Liver function test

Changes in ALT will be used to evaluate effect on liver

Full Information

NCT ID

NCT01459419

First Posted

October 23, 2011

Last Updated

October 23, 2011

Sponsor

Inspira Medical AB

Collaborators

NasVax Ltd

1. Study Identification

Unique Protocol Identification Number

NCT01459419

Brief Title

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

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.

Study Type

Interventional

2. Study Status

Record Verification Date

October 2011

Overall Recruitment Status

Unknown status

Study Start Date

November 2011 (undefined)

Primary Completion Date

May 2013 (Anticipated)

Study Completion Date

October 2013 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Inspira Medical AB

Collaborators

NasVax Ltd

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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.

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Hepatitis C

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

36 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

anti-CD3 monoclonal antibody

Arm Type

Experimental

Arm Description

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

Arm Title

Sodium chloride

Arm Type

Placebo Comparator

Arm Description

Up to 9 subjects will receive placebo. Subjects will receive the drug in a similar manner as as the treatment group

Intervention Type

Drug

Intervention Name(s)

anti-CD3 monoclonal antibody

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Sodium Chloride placebo

Intervention Description

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

Primary Outcome Measure Information:

Title

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.

Description

Time Frame

Secondary Outcome Measure Information:

Title

Decrease in the concentration of HCV

Description

30 days

Time Frame

30 days

Title

Liver function test

Description

Changes in ALT will be used to evaluate effect on liver

Time Frame

30 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Waldemar Halota, Prof.

Phone

+48 52 325 56

kikchzak@cm.umk.pl

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Waldemar Halota, Prof

Organizational Affiliation

Katedra i Klinika Chorób Zakaźnych i Hepatologii Wojewódzki Szpital Obserwacyjno - Zakaźny im. Tadeusza Browicza

Official's Role

Principal Investigator

Facility Information:

Facility Name

Univ.Klinik für Innere Medizin IV

City

Wien

ZIP/Postal Code

A-1090

Country

Austria

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Peter Ferenci, Prof.Dr.

Phone

+43 1 40400 4741

peter.ferenci@meduniwien.ac.at

First Name & Middle Initial & Last Name & Degree

Peter Ferenci, Prof.Dr.

Facility Name

Katedra i Klinika Chorób Zakaźnych i Hepatologii Wojewódzki Szpital Obserwacyjno - Zakaźny im. Tadeusza Browicza

City

Bydgoszcz

ZIP/Postal Code

85 030

Country

Poland

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Waldemar Halota, Prof

Phone

>+48 52 325 5605

kikchzak@cm.umk.pl

First Name & Middle Initial & Last Name & Degree

Waldemar Halota, Prof

12. IPD Sharing Statement

Learn more about this trial

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

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