Sequelae of Viral HepatitisPhase 2NCT00473824

Randomized Phase II Study of Hepatitis C Immune Globulin Intravenous (Human), Civacir(TM), in Liver Transplantation

A Phase 2 study testing Hepatitis C Immune Globulin Intravenous (Human) 5% in people with Sequelae of Viral Hepatitis and Transplantation Infection, run by ADMA Biologics, Inc. at 3 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

A Phase 2 study to evaluate safety, pharmacokinetics and efficacy of Hepatitis C Immune Globulin Intravenous (human) [Civacir(TM)] for preventing or reducing the impact of recurrent HCV infection following liver transplantation. Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Sequelae of Viral Hepatitis, Transplantation Infection, Evidence of Liver Transplantation
What is being tested?: Hepatitis C Immune Globulin Intravenous (Human) 5%
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 7 participants
Where: 3 sitesUnited States
Study dates: May 2007to Feb 2009
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male or female, 18 to 75 years of age.
Written informed consent.
Expectation of compliance with the protocol procedures.
If female, have a negative pregnancy test within 3 days prior to randomization and use an acceptable method of contraception or be at least one year post-menopausal or surgically sterile.
HCV infection identified by positive, quantifiable HCV-RNA test within 3 months prior to transplantation.
First time liver transplant recipient.

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Primary, single organ recipient (deceased donor <65 years of age).
Normal TSH.
Subjects with a pre-LT diagnosis of hepatocellular carcinoma (HCC) may be enrolled provided: there is no evidence of extrahepatic spread, tumor is solitary and <5cm or there are up to three tumors <3 cm.
Agree to receive study medication as outlined in the protocol and follow all study related procedures until the conclusion of their protocol participation.
Agree to consume no alcohol during the entire study period.

Who cannot join

Has received an investigational agent within the last six weeks prior to liver transplantation. Exceptions include Theraspheres for hepatocellular carcinoma or rifaximin.
Known immunoglobulin A deficiency.
Subject weighs more than 112.5 Kg (248 pounds).
Known history of cancer, suspected cancer, or cancer therapy within 12 months prior to the administration of the investigational product, except for treatment for basal cell carcinoma, squamous cell carcinoma, cancer of the cervix in situ, early stage prostate cancer (Gleason's grade 1 or 2), or a history of malignancy where the risk of recurrence is >= 20% within 2 years. A significant exception is hepatocellular carcinoma with predefined acceptability (see inclusion criteria).
Has any condition judged by the study physician to preclude participation in the study, including any psychological disorder, which might hinder compliance.
History of use of immunosuppressive or immunomodulatory drugs within 3 months prior to randomization (except low-dose physiologic replacement glucocorticoid therapy (<=10 mg of prednisone or equivalent per day).

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Recipient of liver from a living donor.
Subjects whose liver is obtained from a non-beating heart donor.
Subjects scheduled to receive a split liver transplantation.
Liver transplants that were obtained from donors across ABO incompatible blood type.
Donor liver cold ischemic time greater than 20 hours.
Donor liver is from a hepatitis C positive donor.
Evidence of any other unresolved infection and any unresolved opportunistic infection requiring treatment.
Serum creatinine level >2.0 times the upper limit of normal or advanced renal disease at screening.
Neutrophil count <1500 cells/mm3, WBC>20,000 x 109/L, Hgb <8 g/dL, or platelet count <25,000 cells/mm3.
Planned use of T-cell depleting antibody therapies.
Hepatitis B (sAg, cAb IgM), hepatitis A (IgM) or HIV infection.
History of autoimmune disease (SLE, scleroderma, RA, etc.).
Women who are pregnant or breast feeding.
The use of colony stimulating factor agents to facilitate subject's entry into study within 2 weeks of enrollment.
History of severe psychiatric disease, especially depression.
Seizure disorders uncontrolled by anticonvulsants (within the last 12 mos).
History of severe cardiac disease, unhealed gastric or duodenal ulcer, or other significant medical disease that would put the subject at risk from the volume of the infusions or significant risk of bleeding from the underlying condition.
Evidence of alcohol and/or drug abuse within 6 months of entry or inability/unwilling-ness to abstain from alcohol throughout entire course of treatment and follow-up.
Concomitant medication with rifabutin, pyrazinamide, isoniazid, thalidomide, oxymetholone (Anadrol).
History of thyroid disease poorly controlled on prescribed medications.
History or other evidence of severe illness or any other conditions which would make the subject, in the opinion of the investigator, unsuitable for Civacir treatment.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

Mayo Clinic
Jacksonville, Florida, 32224
Mayo Clinic
Phoenix, Arizona, 85054
Mayo Clinic
Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: A Randomized, Open-Label Phase II Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of Hepatitis C Immune Globulin Intravenous (Human), Civacir(TM), in Liver Transplant Recipients

Read the detailed description

Hepatitis C virus (HCV) infection is the leading single cause of liver transplantation (LT) in the US and Europe. Recurrence of HCV infection following LT is almost universal. There is currently no effective way to prevent post-transplantation HCV infection of the liver graft and related progression of HCV-related liver disease. This study is designed to evaluate a polyclonal human hepatitis C immune globulin (Civacir) given during and post liver transplantation for preventing or reducing the impact of recurrent HCV infection.

In this open-label trial, 2 subjects will be randomized to receive Civacir (standard of care treatment plus Civacir) for every 1 Control subject (standard of care treatment alone). Civacir recipients will receive 18 intravenous infusions over 24 weeks beginning at the time of liver transplantation.

Viral loads, liver enzyme assessments and liver biopsy assessments will be made at scheduled intervals during the study which will last for 48 weeks.

Conditions: Sequelae of Viral Hepatitis, Transplantation Infection, Evidence of Liver Transplantation
Being tested: Hepatitis C Immune Globulin Intravenous (Human) 5%
Keywords: hepatitis C, liver transplantation, immune globulin
Medical subject headings: Hepatitis C

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Hepatitis C Immune Globulin Intravenous (Human) 5%Biological
Also called Civacir™
Hepatitis C Immune Globulin Intravenous (Human) 5%, [Civacir]: 18 infusions total, per schedule, of 300 or 400 mg/kg of body weight given with standard post-transplant therapy inclusive of immunosuppressive agents.

Study groups in NCT00473824
Study group	Role	What they receive
Civacir Treated	Experimental	Hepatitis C Immune Globulin Intravenous (Human) 5% [Civacir], 18 infusions total, per schedule, of Civacir 300 or 400 mg/kg of body weight, with standard post-transplant site specific routine immunosuppressant therapy . Receives: Biological: Hepatitis C Immune Globulin Intravenous (Human) 5%
Observational Control	No intervention	Observation on standard post-transplant site specific routine immunosuppressant therapy without infusions of Hepatitis C Immune Globulin Intravenous (Human) 5% [Civacir].

What is being measured

The primary outcome is the main question the study is designed to answer.

Post Transplant Reduction in Viral Load (as Measured Quantitatively by Hepatitis C Virus (HCV) Reverse Transcription-Polymerase Chain Reaction (HCV RT-PCR)).
Percentage of subjects who achieve reduction in viral load from the baseline pre-transplant value. Baseline is the pre-transplant HCV viral load as measeured by RT-PCR. Post-transplant HCV viral load is determined at both 1 month and 6 months post-tranplant.
Measured: Outcome evaluations at 1 month (Day 28) and 6 months ( 24 weeks) post-tranplant.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2007Feb 2009

First posted16 May 2007 (estimated)
Study startMay 2007
Primary completionFeb 2009
Study completionFeb 2009

Why it stopped: New sponsor's decision to pursue a redesigned clinical study

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Sequelae of Viral HepatitisStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 7 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00473824
Sponsor's protocol ID: Nabi-3104
Status last verified: Jul 2021
First submitted: 14 May 2007
Last updated: 30 Jul 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Study at a glance

From the registry record, last updated by the sponsor on 30 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Open-Label Phase II Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of Hepatitis C Immune Globulin Intravenous (Human), Civacir(TM), in Liver Transplant Recipients
ClinicalTrials.gov ID: NCT00473824
Acronym / sponsor ID: Nabi-3104
Conditions: Sequelae of Viral Hepatitis, Transplantation Infection, Evidence of Liver Transplantation
Keywords: hepatitis C, liver transplantation, immune globulin
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: New sponsor's decision to pursue a redesigned clinical study
Enrolment: 7 participants (actual)
Lead sponsor: ADMA Biologics, Inc.Industry (pharma, biotech, devices)
Study start: May 2007
Primary completion: Feb 2009 (actual)
Study completion: Feb 2009 (actual)
First posted: 16 May 2007 (estimated)
Results: Posted 7 Feb 2012

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Viral loads, liver enzyme assessments and liver biopsy assessments will be made at scheduled intervals during the study which will last for 48 weeks.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Civacir Treated	Experimental	Biological: Hepatitis C Immune Globulin Intravenous (Human) 5%Hepatitis C Immune Globulin Intravenous (Human) 5% [Civacir], 18 infusions total, per schedule, of Civacir 300 or 400 mg/kg of body weight, with standard post-transplant site specific routine immunosuppressant therapy .
Observational Control	No intervention	–Observation on standard post-transplant site specific routine immunosuppressant therapy without infusions of Hepatitis C Immune Globulin Intravenous (Human) 5% [Civacir].

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (11 listed)

Male or female, 18 to 75 years of age.
Written informed consent.
Expectation of compliance with the protocol procedures.
If female, have a negative pregnancy test within 3 days prior to randomization and use an acceptable method of contraception or be at least one year post-menopausal or surgically sterile.
HCV infection identified by positive, quantifiable HCV-RNA test within 3 months prior to transplantation.

Key exclusion criteria (27 listed)

Has received an investigational agent within the last six weeks prior to liver transplantation. Exceptions include Theraspheres for hepatocellular carcinoma or rifaximin.
Known immunoglobulin A deficiency.
Subject weighs more than 112.5 Kg (248 pounds).
Known history of cancer, suspected cancer, or cancer therapy within 12 months prior to the administration of the investigational product, except for treatment for basal cell carcinoma, squamous cell carcinoma, cancer of the cervix in situ, early stage prostate cancer (Gleason's grade 1 or 2), or a history of malignancy where the risk of recurrence is >= 20% within 2 years. A significant exception is hepatocellular carcinoma with predefined acceptability (see inclusion criteria).
Has any condition judged by the study physician to preclude participation in the study, including any psychological disorder, which might hinder compliance.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Hepatitis C Immune Globulin Intravenous (Human) 5%Also: Civacir™Hepatitis C Immune Globulin Intravenous (Human) 5%, [Civacir]: 18 infusions total, per schedule, of 300 or 400 mg/kg of body weight given with standard post-transplant therapy inclusive of immunosuppressive agents.	Biological	Civacir Treated

Primary outcome

Post Transplant Reduction in Viral Load (as Measured Quantitatively by Hepatitis C Virus (HCV) Reverse Transcription-Polymerase Chain Reaction (HCV RT-PCR)).
Time frame: Outcome evaluations at 1 month (Day 28) and 6 months ( 24 weeks) post-tranplant.
Percentage of subjects who achieve reduction in viral load from the baseline pre-transplant value. Baseline is the pre-transplant HCV viral load as measeured by RT-PCR. Post-transplant HCV viral load is determined at both 1 month and 6 months post-tranplant.

Results and safety

Results posted to the registry on 7 Feb 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Civacir Treatment Arm	5	0
No Civacir (Control)	2	2

Primary outcome: Post Transplant Reduction in Viral Load (as Measured Quantitatively by Hepatitis C Virus (HCV) Reverse Transcription-Polymerase Chain Reaction (HCV RT-PCR)).

Time frame: Outcome evaluations at 1 month (Day 28) and 6 months ( 24 weeks) post-tranplant.. Number. Unit: percentage of participants

Measure	Civacir Treatment Arm n = 5	No Civacir (Control) n = 2
Value	0	0

Population analysed: As the study was terminated early and since no participant in either arm achieved reduction in viral load, it was recorded that zero particpants and zero percent in each arm achieved reduction in viral load.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Civacir Treatment Arm	4 of 5 (80%)	4 of 5 (80%)	Not reported
No Civacir (Control)	0 of 2 (0%)	2 of 2 (100%)	Not reported

Limitations and caveats (from the sponsor): Early termination by sponsor due to data from the initial 7 patients of 36 planned for this study. Therefore, statistical analysis was not performed and no conclusion were reached regarding efficacy or drug safety.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Eliezer Katz, MD study director

Clinical Trial and Consulting Services

Shailesh Chavan, MD study director

Biotest Pharmaceuticals

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 30 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Feb 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Post Transplant Reduction in Viral Load (as Measured Quantitatively by Hepatitis C Virus (HCV) Reverse Transcription-Polymerase Chain Reaction (HCV RT-PCR)). (time frame: Outcome evaluations at 1 month (Day 28) and 6 months ( 24 weeks) post-tranplant.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00473824.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2021.