EASL 2015: Civacir Immune Globulin May Help Prevent HCV Reinfection after Liver Transplant

Civacir, a hepatitis C immune globulin or antibody product, reduced the likelihood of hepatitis C virus infecting the new liver graft after transplantation in patients who were receiving but had not yet completed antiviral treatment, according to preliminary study findings presented at the European Association for the Study of the Liver (EASL) 50th International Liver Congress last month in Vienna.

Without treatment, hepatitis C virus (HCV) almost always infects the donor liver after a transplant, and recurrence is the leading cause of graft loss and liver disease progression. Effective direct-acting antiviral therapy that leads to sustained virological response can prevent reinfection, but people receiving antiviral treatment at the time of transplantation remain at risk.

Norah Terrault from the University of California at San Francisco and colleagues are conducting an ongoing randomized Phase 3 study (Study 988; NCT01804829) to evaluate hepatitis C immune globulin (HCIG or Civacir)for prevention of post-transplant HCV recurrence. Civacir, being developed by Biotest Pharmaceuticals, is a human immune globulin product derived from hundreds of screened blood donors with high HCV antibody levels. Use of multiple donors increases antibody diversity and improves its activity against a variety of HCV strains.

 

This preliminary analysis, presented as a late-breaking poster, included 63 hepatitis C patients with advanced liver disease on the transplant waiting list, enrolled as of late January 2015. More than 80% were men, most were white, and the mean age was 61 years. Most (93%) had HCV genotype 1, with the rest having genotypes 2 or 3. The median MELD score was 19, the median Child-Pugh score was 7, and 77% had hepatocellular carcinoma. People coinfected with hepatitis B and those getting HCV-infected liver grafts were excluded.

Participants could be taking any antiviral regimen that resulted in HCV RNA <100 IU/mL within 4 weeks prior to transplantation. More than 90% received regimens containing sofosbuvir (Sovaldi), including 63% taking sofosbuvir plus ribavirin and 21% taking sofosbuvir plus simeprevir (Olysio); the rest used various interferon-containing regimens. Treatment had been ongoing for a median of 64 days, or just over 9 weeks, at the time of transplantation; nearly half had not yet received the full typical 12-week course of sofosbuvir and none had received the 24-week course recommended for harder-to-treat patients. 15% had detectable HCV viral load at the time of transplantation.

Participants in this this open-label study were randomly assigned to receive either 200 or 300 mg/kg HCIG or else standard-of-care treatment (antivirals only). Those assigned to HCIG received 16 infusions around the time of transplantation and immediately thereafter for a period for 10 weeks.

Results

Preliminary results showed that 1 out of 21 patients (5%) in the HCIG 300 mg/kg arm experienced HCV reinfection after transplantation.

In the HCIG 200 mg/kg and control arms, 7 out of 22 (32%) and 6 out of 20 patients (30%) experienced reinfection, indicating that the lower dose performed no better than not using HCIG at all.

5 out of 9 patients (55%) with detectable HCV viral load in the 200 mg/kg and control arms experienced HCV recurrence.

Anti-HCV antibody titers remained elevated (around 1.5- to 2-fold higher) in the 300 mg/kg HCIG arm relative to the 200 mg/kg and control arms.

HCIG was generally safe and well-tolerated, with no drug-related serious adverse events seen to date.

9 people discontinued treatment early, including 3 due to adverse events.

The most frequently reported adverse events were related to underlying liver disease, surgery-associated events, and symptoms known to be associated with use of human immune globulins such as fever.

"These preliminary results suggest that Civacir 300 mg/kg can increase the proportion of patients on pre-liver transplantation antiviral therapy achieving prevention of HC recurrence post-liver transplantation," the researchers concluded.

They added that this evaluation justified continuing enrollment in the 300 mg/kg arm, but not in the 200 mg/kg low-dose arm, which has been closed.

5/6/15

References

N Terrault, R Shrestha, SK Satapathy, et al. Novel Approach for the Prevention of Recurrent Hepatitis C in Liver Transplant Recipients: Preliminary Results from Ongoing Phase III Trial with Civacir. 2015 International Liver Congress: 50th Annual Meeting of the European Association for the Study of the Liver (EASL). Vienna, April 22-26, 2015. AbstractLP17.

RG Tawar, L Heydmann, J Schuttrumpf
, et al. Civacir Hepatitis C Immune Globulin (HCIG) Potently Neutralizes Infection of Hepatitis C Virus Transplant Escape Variants. 2015 International Liver Congress: 50th Annual Meeting of the European Association for the Study of the Liver (EASL). Vienna, April 22-26, 2015. Abstract P0677.