Clinical trial NCT04575896
Conditions: End Stage Renal Disease Hepatitis C
Sponsor: Johns Hopkins University
Start date: 2020-11-20; Completion date: 2023-12-01
Enrollment: 10 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
In this study, individuals without hepatitis C infection who are on the kidney transplant waitlist will receive a kidney from a deceased donor with hepatitis C infection and will be treated for hepatitis C at the same time. Treatment will include glecaprevir 300 mg / pibrentasvir 120 mg (G-P) administered on-call to the operating room for the renal transplant procedure and continued for 2 weeks post-renal transplant.

Detailed description:
In this study, individuals without hepatitis C infection who are on the kidney transplant waitlist will receive a kidney from a deceased donor with hepatitis C infection and will be treated for hepatitis C at the same time. Treatment will include glecaprevir 300 mg / pibrentasvir 120 mg (G-P) administered on-call to the operating room for the renal transplant procedure and continued for 2 weeks post-renal transplant. The participant will continue to be tested for Hepatitis C for 12 weeks post-treatment.

The primary hypothesis is that prophylactic treatment with glecaprevir/pibrentasvir before and after transplant will prevent the establishment of HCV infection in the recipients of kidneys from HCV-infected deceased donors. Based on the success of preliminary studies, the objective of the study is to evaluate the safety and efficacy of 2 weeks of G-P as prophylaxis for HCV D+/R- kidney transplant.

Arms: arm 1: Participants who receive a kidney from HCV RNA PCR + deceased donor will receive glecaprevir/pibrentasvir 300 mg/120 mg once daily by mouth for 2 weeks
Interventions: intervention 1: Glecaprevir/pibrentasvir
Intervention descriptions: intervention 1: Glecaprevir/pibrentasvir 300mg/120mg once daily by mouth for 2 weeks post-transplant.

Protocol documents:
Prot_SAP_000.pdf: 
Kidney Transplants in Hepatitis C Negative Recipients With 
Hepatitis C Viremic Donors
NCT04575896
September 26, 2023


Date: September 26, 2023 
Principal Investigator: Niraj M. Desai, MD 
Application Number: IRB00237097 
 
JHMIRB eFormA  01 
Version 3 Dated:   06/2007 
 
Page 1 of 17 
 
 
JHM IRB - eForm A – Protocol 
 
Kidney transplants in hepatitis C negative recipients with hepatitis C viremic donors. An open-label, 
non-randomized pilot study to determine the safety and efficacy of two weeks of fixed-dose glecaprevir 
and pibrentasvir as pre- and post-exposure prophylactic therapy. 
 
************************************************************************************************************ 
 
1. 
Abstract 
 
Due to an organ shortage crisis, many individuals with end-stage renal disease will die or become too 
sick to undergo transplantation before receiving a kidney transplant. At the same time, many high 
quality kidneys from hepatitis C infected (HCV+) donors are discarded every year because there is no 
HCV+ waitlist candidate available to accept the organ. New HCV therapies are highly effective and well 
tolerated, with cure rates of nearly 100%. This study is a single center, open-label, pilot interventional 
trial of glecaprevir/pibrentasvir for 10 HCV- nonviremic recipients of kidneys from HCV-infected 
deceased donors at Johns Hopkins Hospital (JHH).  
 
The primary hypothesis is that prophylactic treatment with glecaprevir/pibrentasvir before and after 
transplant will prevent the establishment of HCV infection in the recipients of kidneys from HCV-
infected deceased donors. The safety hypothesis is that grade 3-4 AE related to G-P will occur in ≤ 10% 
of participants. Based on the success of preliminary studies, the objective of this study is to evaluate the 
safety and efficacy of two weeks of glecaprevir/pibrentasvir as prophylactic therapy for HCV D+/R- 
kidney transplantation. 
 
2. 
Objectives 
 
Primary objectives: 
The primary objectives of this study are to evaluate the safety and efficacy of glecaprevir 300 
mg/pibrentasvir 120 mg (G-P) treatment in HCV-nonviremic transplant recipients (HCV R-) of a kidney 
from an HCV-infected deceased donor (HCV D+). G-P will be administered on-call to the operating 
room (OR) for the kidney transplant procedure and continued for 2 weeks after the kidney transplant. 
• The primary efficacy outcome will be the proportion of HCV D+/R- renal transplant recipients 
with undetectable HCV plasma RNA at 12 weeks after treatment (14 weeks after kidney 
transplant). 
• The primary safety outcome will be the incidence of adverse events (AE) related to G-P. 
 
Secondary outcomes: 
• Proportion of kidney transplant recipients who have undetectable HCV plasma RNA at 1, 2, 4 and 
12 weeks after discontinuation of therapy.  
• Proportion of kidney transplant recipients who become reactive for HCV antibodies following 
transplant. 
• Kidney allograft function at 6 and 12 months and 24 months following transplantation, including 
creatinine, glomerular filtration rate and assessment of protein in the urine. 
 
 


Date: September 26, 2023 
Principal Investigator: Niraj M. Desai, MD 
Application Number: IRB00237097 
 
JHMIRB eFormA  01 
Version 3 Dated:   06/2007 
 
Page 2 of 17 
 
3. 
Background  
 
As of March 20, 2020, there are 94,874 individuals awaiting a life-saving kidney transplant in the 
United States; however, due to a shortage of donor organs, only 23,400 kidney transplants were 
performed in 2019 [1]. Waiting times in the United States for a kidney transplant average 5 years and up 
to half of all individuals on the waiting list will die or become too sick to undergo the procedure. 
Mortality on the kidney transplant waiting list is 6% per year with significant variation depending on 
patient characteristics and the geographic location where the patient lives. The death rate on the kidney 
waiting list for older individuals and for individuals with diabetes is approximately 10% per year. 
Therefore, a patient over 60 years of age with an estimated waitlist time of five years for a kidney has a 
50% chance of death before a kidney becomes available [2,3]. 
 
Kidneys from hepatitis C-infected (HCV+) donors are currently underutilized. From 2014-16, over 40% 
of kidneys from HCV+ deceased donors were discarded, compared to 18% of kidneys from HCV-
uninfected (HCV-) donors. Many of these HCV+ organs are of excellent quality, but are frequently 
discarded due to a lack of hepatitis C-infected waitlist candidates [4]. 
 
One strategy to expand the kidney donor pool is to transplant HCV+ donor kidneys into HCV- recipients 
(HCV D+/R- transplant) in combination with direct-acting antivirals (DAAs) to treat HCV. In 2016, we 
performed the first study in the world using this strategy at Hopkins (EXPANDER: An open-label study 
to determine the efficacy and safety of fixed-dose grazoprevir/elbasvir treatment in hepatitis C 
uninfected recipients of renal transplants from hepatitis C infected deceased donors. IRB 00089751; 
NCT# 02781649). This study was a pilot trial of this approach in 10 HCV-uninfected kidney transplant 
recipients using DAAs as pre- and post-transplant prophylaxis. Depending on the donor HCV genotype, 
the DAAs grazoprevir/elbasvir with or without sofosbuvir were used. In this trial, HCV- recipients were 
given the first dose of DAAs just prior to the transplant procedure and were subsequently treated with 
standard treatment durations of 12-16 weeks (depending on donor HCV genotype) of DAAs after 
transplant. The length of DAA therapy was based on the kidney donor’s HCV genotype. Ten HCV 
D+/R- transplants were performed at Johns Hopkins and this approach was successful in preventing 
chronic hepatitis C infection in all 10 recipients. The DAAs were well tolerated and there were no grade 
3 or grade 4 serious adverse events noted [5]. 
 
In addition to the study described above, a similar study at the University of Pennsylvania treated 10 
HCV negative participants receiving an HCV+ donor kidney with elbasvir-grazoprevir for 12 weeks and 
reported SVR in all 10 participants at week 12 post treatment [6]. In contrast to the Hopkins 
EXPANDER study where a prophylactic strategy was used to treat donor-derived hepatitis C infection 
in recipients, the Penn study used a pre-emptive approach, waiting for recipients to have detectable HCV 
RNA in the blood prior to initiating DAA therapy. In that trial, 10/10 patients had detectable HCV RNA 
in peripheral blood by day 3. All patients were cured with 12 weeks of DAA therapy [6]. 
 
An important finding in the EXPANDER study was the short duration and low level of viremia observed 
in transplant recipients when DAA treatment was initiated just prior to the transplant procedure. In 
contrast, the U Penn group observed much higher levels of persistent hepatitis C viremia in their study 
where DAA therapy was delayed for several days. We hypothesized that shorter duration DAA therapy 
would be successful and tested this hypothesis in a recently completed study (Renal transplants in 
hepatitis C negative recipients with nucleic acid positive donors, IRB00174409; NCT#03627299). In 
this study we used the once daily, fixed-dose combination of the NS3/4A protease inhibitor glecaprevir 


Date: September 26, 2023 
Principal Investigator: Niraj M. Desai, MD 
Application Number: IRB00237097 
 
JHMIRB eFormA  01 
Version 3 Dated:   06/2007 
 
Page 3 of 17 
 
(G) and the NS5A inhibitor pibrentasvir (P) as the DAA. This medication was newly approved for the 
treatment of all hepatitis C genotypes (1-6) and is not metabolized by the kidneys. Thus, it was felt to be 
the best regimen to use as pre- and post-exposure prophylaxis in the early post-kidney transplant period 
[7].  
 
In this recently completed study with 4 weeks of DAA treatment, all ten recipients completed 4 weeks of 
G-P following transplantation as well as 12 weeks of follow-up after completing DAA therapy. All 10 
patients cleared hepatitis C and remained HCV negative throughout the follow-up period. All 10 patients 
had excellent kidney graft function through 6 months of follow-up; however, one patient did lose kidney 
transplant function approximately 8 months after transplantation due to a late renal vein thrombosis that 
was unrelated to hepatitis C or to DAA treatment. Of note, only 5 of 10 recipients showed any evidence 
of hepatitis C viremia during the early post-op period and the highest quantifiable viral loads observed 
were on postoperative day 1 in three patients (post-operative day 1 hepatitis C viral loads: 161, 153, and 
87 IU/ml). All recipients were clear of hepatitis C after the first week following transplantation [8]. 
 
Based on the success of these preliminary studies, the objective of our current study is to evaluate the 
safety and efficacy of two weeks of glecaprevir/pibrentasvir as prophylaxis for HCV D+/R- kidney 
transplantation. 
 
4. 
Study Procedures 
 
This is a single center, open-label, pilot trial of glecaprevir/pibrentasvir for 10 HCV- nonviremic 
recipients (R-) of kidneys from HCV-infected deceased donors (HCV D+) at Johns Hopkins Hospital 
(JHH). Individuals who meet the inclusion criteria will be offered enrollment. Informed consent will be 
obtained by a physician on the study team and those who provide informed consent will be enrolled. All 
participants will be initiated on oral, once-daily, fixed-dose G-P starting on call to the operating room 
for the kidney transplant. 
 
Screening Phase: HCV RNA negative individuals on the kidney transplant waiting list at Johns 
Hopkins Hospital (JHH) will be recruited and screened for eligibility. Individuals who are interested in 
the study will give informed consent. We will approach HCV negative individuals on the deceased 
donor kidney transplant waitlist who meet the recipient inclusion criteria. Currently there are over 500 
individuals meeting these criteria at JHH. At JHH, approximately 50% of current waitlist candidates will 
accept Infectious Risk Donors (IRDs). We anticipate a lower acceptance rate of HCV+ deceased donors 
and estimate a 20% participation rate. Thus, we estimate having a pool of at least 50 eligible screened 
participants and our consenting target is 25, with 10 subjects enrolled and transplanted. Once a patient 
signs a consent form, a unique baseline number will be assigned for identification purposes. Prior to 
transplantation, data on demographics (age, sex, race, etc.), medical history, social history, and renal 
biopsy diagnosis (when available) will be collected.  
 
We estimate 2 months for screening and consenting a pool of 20 eligible patients. At JH the approximate 
wait time for an HCV+ deceased donor is approximately 6 months. Therefore, we anticipate an average 
of one HCV D+/R- transplant per month, with an accrual period of 12 months. Total study duration will 
therefore be 24 months. 
 
Accrual Objective: 10 participants  Accrual Period: 12 months  Total Study Duration: 24 months 
Long-term follow-up at 2-years: 24 months 


Date: September 26, 2023 
Principal Investigator: Niraj M. Desai, MD 
Application Number: IRB00237097 
 
JHMIRB eFormA  01 
Version 3 Dated:   06/2007 
 
Page 4 of 17 
 
 
HCV+ Donor Identification: Those who provide informed consent for the study will be listed in the 
United Network for Organ Sharing (UNOS) with a status of “willing to accept an HCV+ organ”. The 
JHH transplant team will then receive HCV+ donor kidney offers for the study participant from Organ 
Procurement Organizations (OPOs). If an HCV+ donor who meets the inclusion criteria is identified, the 
study participants will be offered the organ and, if they accept, they will become an active treatment 
participant. A donor blood sample will be obtained from the OPO for the purposes of this study. 
Currently, offering OPOs only perform a qualitative HCV RNA by nucleic acid testing. HCV 
quantification and genotyping are not performed on donors, and no FDA approved assays exist for this 
indication in organ donors. Donor HCV RNA quantification and HCV genotyping will be performed in 
parallel with the transplantation and initiation of treatment. The OPO will ship a donor blood sample to 
JHH for HCV genotyping and HCV RNA quantification. Plasma will be banked for future resistance 
testing if needed. 


Date: September 26, 2023 
Principal Investigator: Niraj M. Desai, MD 
Application Number: IRB00237097 
 
JHMIRB eFormA  01 
Version 3 Dated:   06/2007 
 
Page 5 of 17 
 
Screening, enrollment and treatment (Figure 1) 
  
 
 
 
  
 
 
 
 
Donor HCV genotype testing 
Donor HCV viral load 
Donor Inclusion Criteria 
•
Age 13-60 
•
Projected CIT ≤ 40 hrs 
•
CR < 10.0 mg/dL 
•
Normal renal biopsy other than ATN 
•
HCV RNA+ qualitative NAT 
Active Treatment Arm (n = 10) 
G/P on call to OR 
HVC D+ to HCV R- kidney transplant 
G/P treatment - 2 weeks 
Recipient HCV testing post-transplant 
Recipient Inclusion Criteria 
• 
Age > 18 years old 
• 
On dialysis or GFR < 15 ml/min 
• 
On deceased donor transplant waitlist 
• 
No cleared living donor options 
• 
HCV RNA negative  
Recipient education 
Obtain informed consent 
Change UNOS listing to accept HCV + donor 


Date: September 26, 2023 
Principal Investigator: Niraj M. Desai, MD 
Application Number: IRB00237097 
 
JHMIRB eFormA  01 
Version 3 Dated:   06/2007 
 
Page 6 of 17 
 
Active Phase, Transplant and Treatment: At the time of transplant admission, the kidney recipient 
will undergo the standard pre-operative work-up, including laboratory testing, chest X-ray, EKG, and 
urinalysis (if applicable). In addition, a sample for baseline HCV serology will be drawn if not 
performed within the past 12 months. Donor and recipient crossmatch will be performed using T cell 
and B cell complement-dependent cytotoxicity crossmatch. In addition, quantitative assessment for the 
presence of donor specific antibody will be performed by solid phase assay (Luminex) and confirmed to 
be below a flow positive level. Once a recipient is deemed appropriate to undergo the kidney transplant 
procedure and the HCV+ donor organ has been examined and found to be acceptable for transplant, the 
recipient will be called to the operating room. The initial dose of G-P will be administered to the 
recipient when called to the operating room (see treatment strategy below). 
 
The deceased donor kidney transplant procedure will be performed in the standard manner under general 
anesthesia with appropriate monitoring lines. Intraoperative medications will include intravenous 
cefazolin, heparin, mannitol, and furosemide. Anesthetic medications include inhalational agents, 
muscle relaxant, and narcotic pain medication. Other standard medications will be administered as well. 
Induction immunosuppression administered in the operating room will consist of intravenous 
Solumedrol (500 mg) and intravenous rabbit anti-thymocyte globulin (1.5 mg/kg) (Thymoglobulin, 
Genzyme). During the transplant operation, a surgical drain(s), ureteral stent, and urinary catheter will 
be placed. 
 
Postoperative care will be performed in the standard manner in a monitored, step-down intensive care 
unit setting. Ongoing induction immunosuppression with daily Solumedrol and Thymoglobulin for three 
post-operative doses each will be administered per JHH protocol. In addition, maintenance 
immunosuppressive therapy consisting of tacrolimus, mycophenolate mofetil, and prednisone will be 
initiated. Tacrolimus dosing will be adjusted to obtain a serum trough concentration between 7-10 ng/ml 
for the first three months postoperatively and then 6-8 ng/ml beyond three months. Mycophenolate 
mofetil will be administered in divided doses for a total dose of 1000-2000 mg daily. Prednisone will be 
initiated at a dose of 20 mg daily once the initial course of Solumedrol is completed and gradually 
tapered to 5 mg daily by 6-12 weeks. 
 
Standard post-transplant prophylaxis strategies will be used in subjects for the prevention of 
opportunistic infections. These include trimethoprim-sulfamethoxazole (Bactrim) for pneumocystis 
pneumonia prophylaxis, valganciclovir for cytomegalovirus infection in cases of CMV seropositive 
donors and/or recipients, and fluconazole for fungal prophylaxis. 
 
Additional postoperative care will be performed in the standard manner and include intravenous fluids to 
replace urine output for the first 24 hours postoperatively. Early mobilization and ambulation will be 
encouraged. Diet advancement will start with clear liquids several hours after surgery and progress to a 
regular diet by approximately 24 hours after surgery. The urinary catheter will remain in place for 3-7 
days after surgery, depending on the condition of the patient’s bladder at the time of the transplant 
operation. Surgical drain(s) placed at the time of the transplant procedure remain(s) in place until daily 
output is below 50 ml per day. The ureteral stent is removed by cystoscopy approximately 4-8 weeks 
after surgery. 
 
Discharge from the hospital is typically between 5 and 10 days postoperatively, once renal transplant 
function is established, the patient is tolerating a regular diet, having normal bowel and bladder function, 
and has a satisfactory understanding of post-transplant care. During the hospitalization, teaching of 


Date: September 26, 2023 
Principal Investigator: Niraj M. Desai, MD 
Application Number: IRB00237097 
 
JHMIRB eFormA  01 
Version 3 Dated:   06/2007 
 
Page 7 of 17 
 
transplant medications and planned follow-up will occur on several occasions. Included in this teaching 
will be the medication and follow-up labs and visits related to the study protocol. 
 
Treatment Strategy: The study participant will be admitted to the hospital and undergo standard 
recipient admission work-up. Once this work-up is completed, crossmatch results are available, and 
relevant donor kidney information is available (including examination of the kidney in the operating 
room to confirm anatomic suitability for transplantation), the first dose of G-P will be administered 
when the recipient is called to the operating room (typically 1-3 hours prior to start of surgery). Post-
transplant, G-P will be continued daily at 10 AM to correspond with the inpatient daily dosing nurse 
medication administration. To ensure timely delivery daily at 10 AM, the first dose post-operatively may 
occur before, but not after, 36 hours. For example, if the participant received the first dose pre-transplant 
at 2:00 PM, the second dose will take place 20 hours later on post-operative day #1 at 10:00 AM. Most 
renal transplant recipients are extubated in the operating room and able to take oral medications within 
eight hours after the transplant procedure. During the hospitalization, G-P will be given once daily.  
 
Visit Schedule: Study visits will occur at days 0, 1, 4, 7, treatment week 2, and follow-up weeks (FW) 
1, 2, 4 and 12 for all participants. Post-transplant data collection will include the laboratory data 
indicated in the Schedule of Events (Table 1). We will also collect immunosuppression regimen, 
tacrolimus trough, creatinine level, acquisition of opportunistic infections, graft survival and patient 
survival. Allograft biopsies will be performed if there is concern for rejection or other causes of graft 
dysfunction. Allograft biopsies will be classified by the Banff criteria. 
 
Year 2 Long-Term Follow-Up: As of August 18, 2022, all 10 subjects were accrued and completed the 
1-year study. The study team proposes a minimal risk long-term follow-up in order to capture survival, 
rejection, graft failure, and eGFR data from the EMR at 2-years post-transplant. We will call previously 
enrolled subjects that consented for Future Contact to gauge their interest and obtain oral consent for the 
collection and use of their health information through the 24 month timepoint. No procedures are 
involved; chart review only. We will use an oral consent script. 
 
Treatment and follow-up strategy (Figure 2) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Post-Transplant Visits 
Pre-Transplant 
First dose of G/P ~ 3 
hours pre-transplant 
G-P x 2 
weeks 
HCV Plasma RNA Measurement 
FW4 
FW4 
FW2 
TW2 FW1 
TD  0   1   4  7 
FW2 
FW1 
TW2 
FW12 
FW12 


Date: September 26, 2023 
Principal Investigator: Niraj M. Desai, MD 
Application Number: IRB00237097 
 
JHMIRB eFormA  01 
Version 3 Dated:   06/2007 
 
Page 8 of 17 
 
 
 
TD = treatment day, TW = treatment week, FW = follow-up week  


Date: September 26, 2023 
Principal Investigator: Niraj M. Desai, MD 
Application Number: IRB00237097 
 
JHMIRB eFormA  01 
Version 3 Dated:   06/2007 
 
Page 9 of 17 
 
Schedule of Events (Table 1) 
 
 
Baseline POD 1, 4, 
7 
TW  
2 
FW 
1 
FW 
2 
FW 
  4 
FW 
12 
Donor HCV genotypea 
X 
 
 
 
 
 
 
Donor HCV quant RNAb 
X 
 
 
 
 
 
 
Recipient HCV RNAb 
X 
X 
X 
X 
X 
X 
X 
Recipient HCV Serologyc 
X 
 
 
 
 
 
X 
Recipient Hematologyd 
X 
X 
X 
X 
X 
X 
X 
Recipient Chemistrye 
X 
X 
X 
X 
X 
X 
X 
Recipient Physical exam 
X 
 
X 
 
X 
X 
X 
POD post-operative day; TW treatment week; FW follow up week 
aHCV genotype and subtype will be determined 
bHCV RNA will be measured using an FDA approved assay in a CLIA certified lab. 
cHCV antibody testing using an FDA approved assay in a CLIA certified lab. 
dHematocrit, Hemoglobin, platelet count, red blood cell count, white blood cell count– standard of care 
eAlanine aminotransferase, aspartate aminotransferase, albumin, alkaline phosphatase, creatinine, total bilirubin, 
glucose, potassium, and sodium– standard of care 
 
Adverse Event Reporting: Adverse event reporting will follow the requirements outlined below. 
Adverse events will also be recorded and tracked in a safety monitoring database by the investigators. 
Serious adverse events will be reported to the Institutional Review Board at Johns Hopkins University 
according to IRB guidelines and to the sponsor. 
 
Participants undergoing solid organ transplantation will be expected to have frequent adverse events 
(AEs) related to the organ transplant surgery and immunosuppressants, which are not the subject of this 
protocol. This protocol focuses on the use of G-P. Grade 3 and Grade 4 AEs and SAEs related to the use 
of G-P will be collected.   
 
All Grade 3 or 4 AEs and all SAEs will be reviewed by the principal investigator as they occur in a 
timely manner. All serious adverse events (SAEs) will be reported to the IRB. Grade 3 or higher AEs 
that are possibly or definitely related to G-P will be reported to the IRB.   
 
Adverse Event (AE) Definition  
Any untoward or unfavorable medical occurrence associated with the participant’s participation in the 
research, whether or not considered related to the participant’s participation in the research (modified 
from the definition of adverse events in the 1996 International Conference on Harmonization E-6 
Guidelines for Good Clinical Practice) (from OHRP "Guidance on Reviewing and Reporting 
Unanticipated Problems Involving Risks to Participants or Others and Adverse Events (1/15/07)" 
http://www.hhs.gov/ohrp/policy/advevntguid.html#Q2 )  
 
For this study, an adverse event will include any untoward or unfavorable medical occurrence associated 
with, but not limited to:   
1. Worsening (change in nature, severity or frequency) of conditions present at the onset of the 
study 
2. Intercurrent illnesses 
3. Infections 


Date: September 26, 2023 
Principal Investigator: Niraj M. Desai, MD 
Application Number: IRB00237097 
 
JHMIRB eFormA  01 
Version 3 Dated:   06/2007 
 
Page 10 of 17 
 
4. Abnormal laboratory values (significant shifts from baseline within the range of normal that the 
investigator considers to be clinically important) 
5. Clinically significant abnormalities in physical examination, vital signs, weight, and/or tests and 
procedures 
6. Surgical complications  
 
Serious Adverse Event (SAE) Definition  
An adverse event or suspected adverse reaction is considered “serious” if, in the view of the investigator 
it results in any of the following outcomes (21 CFR 312.32(a)): 
1. Death 
2. A life-threatening event: An AE or SAR is considered “life-threatening” if, in the view of the 
investigator, its occurrence places the participant at immediate risk of death. It does not include 
an AE or SAR that, had it occurred in a more severe form, might have caused death.  
3. Inpatient hospitalization or prolongation of existing hospitalization 
4. Persistent or significant incapacity or substantial disruption of the ability to conduct normal life 
functions 
5. Congenital anomaly or birth defect 
6. Important medical events that may not result in death, be life threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical judgment, they 
may jeopardize the participant and may require medical or surgical intervention to prevent one of 
the outcomes listed above 
 
Grading and Attribution of Adverse Events 
 
Grading Criteria: 
AEs will be graded according to the criteria set forth in the National Cancer Institute’s Common 
Terminology Criteria for Adverse Events (CTCAE) version 4.0.  This document (referred to herein as 
the NCI-CTCAE manual) provides a common language to describe levels of severity, to analyze and 
interpret data, and to articulate the clinical significance of all adverse events.  
 
Adverse events will be graded on a scale from 1 to 5 according to the following standards in the NCI-
CTCAE manual: 
Grade 1 = mild adverse event. 
Grade 2 = moderate adverse event. 
Grade 3 = severe and undesirable adverse event. 
Grade 4 = life-threatening or disabling adverse event. 
Grade 5 = death. 
 
Events grade 3 or higher that are possibly or definitely related to study procedures or intervention will 
be collected on AE case report. 
 
Attribution Definitions: 
The relationship, or attribution, of an adverse event to the study intervention or study procedures will 
initially be determined by the investigator.  For additional information and a printable version of the 
NCI-CTCAE manual, consult the NCI-CTCAE web site: http://ctep.cancer.gov/reporting/ctc.html. 
 


Date: September 26, 2023 
Principal Investigator: Niraj M. Desai, MD 
Application Number: IRB00237097 
 
JHMIRB eFormA  01 
Version 3 Dated:   06/2007 
 
Page 11 of 17 
 
Unrelated: The adverse event is clearly not related; there is insufficient evidence to suggest a 
causal relationship. 
 
Possibly Related: The adverse event has a reasonable possibility to be related; there is evidence 
to suggest a causal relationship. 
 
Definitely Related: The adverse event is clearly related. 
 
Collection and Recording of Adverse Events 
 
Collection Period 
Serious adverse events will be collected from the time of first dose of study medication until a 
participant completes study participation, or until 30 days after the participant prematurely withdraws 
(without withdrawing consent) or is withdrawn from the study. Grade 3 or higher AEs will be reviewed 
by the investigator and will be reported if they are possibly or definitely related to the study medication. 
 
Collecting Adverse Events 
Adverse events (including SAEs) may be discovered through any of these methods: 
1. Observing the participant 
2. Interviewing the participant [e.g., using a checklist, structured questioning, diary, etc.] 
3. Receiving an unsolicited complaint from the participant 
4. In addition, an abnormal value or result from a clinical or laboratory evaluation can also indicate 
an adverse event, as defined in Section 2.9.3, Grading and Attribution of Adverse Events 
 
Recording Adverse Events 
Throughout the study, the investigator will review all grade 3 or higher AEs and if potentially related to 
a study medication, will report them to the IRB. All SAEs will be reported to the IRB. 
 
Once reported, an AE/SAE will be followed until it resolves with or without sequelae, or until the end of 
study participation, or until 30 days after the participant prematurely withdraws (without withdrawing 
consent) or is withdrawn from the study, whichever occurs first. 
 
Reporting of Serious Adverse Events and Adverse Events 
Adverse Events and Serious Adverse Events Exempt from Reporting: 
1. Any AE lower than grade 3 
 
Reporting of Other Safety Information 
An investigator shall promptly notify the site IRB when an “unanticipated problem involving risks to 
participants or others” is identified, which is not otherwise reportable as an adverse event 
 
5. 
Inclusion/Exclusion Criteria 
 
Recipient Inclusion Criteria 
1. Participants ≥ 18 years old 
2. On the deceased donor kidney waitlist at Johns Hopkins Hospital 
3. Awaiting a first or second kidney transplant 
4. No cleared living kidney donors 


Date: September 26, 2023 
Principal Investigator: Niraj M. Desai, MD 
Application Number: IRB00237097 
 
JHMIRB eFormA  01 
Version 3 Dated:   06/2007 
 
Page 12 of 17 
 
5. On hemodialysis or peritoneal dialysis or stage 5 CKD defined as a glomerular filtration rate <15 
ml/min for ≥ past 90 days 
6. HCV- nonviremic (by HCV RNA PCR) and without any behavioral risk factors for contracting 
HCV other than being on hemodialysis 
7. Calculated panel reactive anti-HLA antibody (flow cPRA) below 80%  
 
Recipient Exclusion Criteria 
1. Plan to receive a multi-organ transplant  
2. Plan to receive a dual kidney transplant (including en bloc) 
3. Participating in another study that involves an intervention or investigational product 
4. Plan to receive a blood type incompatible kidney 
5. History of human immunodeficiency (HIV), hepatitis C (HCV), or active hepatitis B (HBV) 
infection, defined as being on active antiviral treatment for HBV, detectable hepatitis B surface 
Ag or detectable hepatitis B DNA 
6. Unable to safely substitute or discontinue a medication that is contraindicated with the study 
medication 
7. Psychiatric or physical illness that in the opinion of the investigator would make it unsafe to 
proceed with transplantation or interfere with the ability of the subject to participate in the study  
 
Donor Inclusion Criteria 
1. Donor age 13-60 years 
2. Donation after brain death or donation after cardiac death donor 
3. Projected cold ischemia time of 40 hours or less 
4. Terminal creatinine less than 10.0 mg/dL 
5. No evidence of significant chronic pathologic findings on pre-implantation biopsy 
6. HCV positive by nucleic acid (RNA) testing 
 
6. 
Drugs/ Substances/ Devices 
Co-formulated glecaprevir 300 mg/pibrentasvir 120 mg will be provided by the study, dispensed from 
the Investigational Drug Service (IDS). The G-P orally will be initiated on call to the operating room for 
kidney transplantation. Dosing will continue every 24 hours postoperatively through week 2 after 
transplantation for donors with any genotype of HCV (genotypes 1-6). 
 
Rescue Treatment  
With the availability of a pan-genotypic HCV medication that is safe to use with renal dysfunction, we 
expect all recipients to be adequately treated with G-P. However, we will perform genotyping on the 
donor blood sample in order to help guide therapy if there is a treatment failure. Based on the results of 
our initial studies using this strategy (EXPANDER, REHANNA), we expect 70 percent of donors to 
have genotype 1 and the other 30% to be have genotype 2 or 3. 
 
If a treatment failure were to occur, recipient genotype and mutation analysis would be performed and 
the most recent AASLD/IDSA HCV treatment guidelines (hcvguidelines.org) would be followed to 
select the most appropriate regimen to use in any cases of HCV infection. This would be considered 
clinical care.   
 
 
7. 
Study Statistics 


Date: September 26, 2023 
Principal Investigator: Niraj M. Desai, MD 
Application Number: IRB00237097 
 
JHMIRB eFormA  01 
Version 3 Dated:   06/2007 
 
Page 13 of 17 
 
 
A. Primary Outcome Variable: 
• The primary outcome will be the proportion of kidney transplant recipients with undetectable 
plasma HCV RNA at 12 weeks after stopping treatment. 
 
B. Secondary Outcome Variables: 
• Detection of HCV antibodies 
• Allograft function at 6 and 12 months 
• If there are transplant recipients with detectable plasma HCV RNA after treatment or if there is 
viral breakthrough on treatment, we will measure prevalence of NS3 and NS5A mutations in 
HCV from the recipient plasma. Mutation testing will be guided by the HCV genotype that is 
present. 
 
C. Statistical plan including sample size justification and interim data analysis: 
The Johns Hopkins group will be responsible for collecting data, maintaining the database, and data 
analysis. Both our transplant surgery and transplant infectious disease group have extensive 
experience leading hepatitis C treatment studies and multicenter NIH-funded studies examining 
outcomes in transplant.   
 
Our Transplant Infectious Disease Group has an active prospective database collecting outcomes, 
including infectious complications, on the JH cohort of all solid organ transplant recipients. The 
cohort design facilitates use of standardized outcomes definitions, prospective capture of event-
driven data, and collection of information after discharge from the referral center. Expanding on 
these existing protocols and infrastructure, we will leverage infrastructure and resources from the 
Department of Surgery clinical research unit and the JH Comprehensive Transplant Center (CTC) 
for the planned study. Moreover, the JH Transplant and Oncology Infectious Diseases Clinical 
Research Coordinating Center (Infectious Diseases) has committed support for document 
development and regulatory support. These groups have staff dedicated to regulatory oversight and 
development and compliance with reporting requirements and we have successfully collaborated 
already in generating the preliminary data shown above. 
 
Data Collection Mechanism:   
Data collection will be performed using the REDCap electronic data collection and storage hosted by 
Johns Hopkins University. All data in REDCap will be de-identified. Each site will maintain a 
record of which subject corresponds to subject numbers assigned by REDCap. This file will be 
password protected if electronic or kept in a locked location if in the subject binder. 
 
In brief, the REDCap Consortium consists of 84 institutional partners from CTSA, GCRC, RCMI 
and other institutions, in which JH is an active participant. It was developed by CTSA partners at 
Vanderbilt, with the goal of enabling investigator research through the establishment of a more user-
friendly database system. This consortium supports two secure web-based applications designed to 
enable data capture for research studies. The software contains an intuitive interface for collecting 
data with data validation commands, allows for automated export procedures to statistical packages 
(e.g. SAS) and provides advanced features that allow for branching logic, file uploading, etc. The 
system itself is supported on MySQL, an open source database similar to SQL/Oracle, and operates 
on a web-based system. All servers are backed-up at each data center (institution) and include 
password protection to provide enhanced security while maintaining accessibility via the internet. 


Date: September 26, 2023 
Principal Investigator: Niraj M. Desai, MD 
Application Number: IRB00237097 
 
JHMIRB eFormA  01 
Version 3 Dated:   06/2007 
 
Page 14 of 17 
 
 
Data Monitoring:  
Upon enrollment of subjects, the REDCap database constructs a calendar of anticipated events, 
which includes completion of follow-up case report forms, with electronic reminders 
 
Power/Sample Size:   
Figure 4. We hypothesize that the treatment strategy will be 100% effective and that the HCV 
RNA<LLOQ in all 10 patients. Given that this is a pilot study with no comparison group, the power 
to detect a difference depends on the true efficacy. For example, if the true efficacy is 79%, then we 
will have at least one observed outcome 90.53% of the time (1-.79^10). Figure 4 demonstrates the 
relationship between the true efficacy and the power of the proposed study. 
 
 
 
 
8. 
Risks 
 
A. Medical Risks: 
Although it has not been reported, due to acute infection with hepatitis C, there is a slight risk of 
acquiring hepatitis C, fulminant hepatitis, and death.  
 
Glecaprevir/Pibrentasvir: 
The most common side effects with these drugs are nausea, headache, and fatigue. 
 
Blood Draw: 
Taking blood may cause discomfort, bleeding or bruising where the needle enters the body. In rare 
cases, it may result in fainting. There is a small risk of infection. 
 
Pregnancy: To date there is no adequate human data available to establish whether or not the study 
drug poses a risk to an embryo or fetus. To ensure patient safety, study treatment must be 
discontinued and the subject withdrawn if pregnancy occurs while the patient is on study treatment. 
Women, and men with female partners capable of becoming pregnant, must use effective methods 
of birth control. 
 
B. Steps taken to minimize the risks: 
 
Medication Side Effects: 


Date: September 26, 2023 
Principal Investigator: Niraj M. Desai, MD 
Application Number: IRB00237097 
 
JHMIRB eFormA  01 
Version 3 Dated:   06/2007 
 
Page 15 of 17 
 
Participants will be monitored closely and instructed to report any change in their medical condition 
promptly. Side effects will be assessed and managed as clinically indicated.  
 
Blood Draw: 
Only properly trained clinical staff will draw blood. The amount of blood collected is the minimal 
amount for proper analysis. 
 
Pregnancy: 
Women only:  
Women who can get pregnant should not take study drug(s) unless they and their partner do not 
have intercourse ever or are using 2 methods of birth control for the duration of the study (starting 3 
weeks prior to the Day 1 visit) and for a minimum of 6 months after last dose of study drug or 
longer as directed by your study doctor. 
 
At least one method of birth control must be a condom.  
 
Women who can get pregnant must have a negative pregnancy test at time of admission for 
transplant, and prior to taking the first dose of study drug.  
 
Female subjects must notify the study team if they become pregnant while in this study and for 6 
months after stopping the study drug, or for as long as directed by the study doctor to use 
contraception. In the event of a positive urine pregnancy result, subjects will be instructed to return 
to the study clinic as soon as possible for a serum (blood) pregnancy test.  
 
Men only:  
If male subjects have a female partner who cannot become pregnant, they must still consistently and 
correctly use a condom.  
 
If male subjects have a female partner who can become pregnant, subject must use two forms of 
birth control for the entire study and for a minimum of 6 months after the last dose of study drug. 
 
Male participants must also agree not to donate sperm from the time of first dose of study drug until 
6 months after the last dose of study drug. 
 
C. Plan for reporting unanticipated problems or study deviations: 
Recording Adverse Events: 
Throughout the study, the investigator will review all grade 3 or higher AEs and if potentially related 
to a study medication, will report them to the IRB. All SAEs will be reported to the IRB. Once 
reported, an AE/SAE will be followed until it resolves with or without sequelae, or until the end of 
study participation, or until 30 days after the participant prematurely withdraws (without 
withdrawing consent) or is withdrawn from the study, whichever occurs first.  
 
Reporting of Other Safety Information: 
An investigator shall promptly notify the site IRB when an “unanticipated problem involving risks to 
participants or others” is identified, which is not otherwise reportable as an adverse event. 
 
D. Legal risks such as the risks that would be associated with breach of confidentiality: 


Date: September 26, 2023 
Principal Investigator: Niraj M. Desai, MD 
Application Number: IRB00237097 
 
JHMIRB eFormA  01 
Version 3 Dated:   06/2007 
 
Page 16 of 17 
 
The principal legal risk regarding a breach of confidentiality of subjects on this study concerns 
responsibility for potential retribution by the subject’s employer or insurance company to their 
medical condition and risks associated with this research. A variety of mechanisms have been 
established to protect the confidentiality of medical records and data procured in this project. Access 
to the database is controlled through passwords. Access to the work site is controlled through 
passkeys. Although the study team will maintain a password-protected spreadsheet linking subject 
numbers to identifiable patient information, any research generated will be completely de-identified 
for reporting purposes. 
 
E. Financial risks to the participants: 
The subject will receive the Insurance and Research Participant Financial Responsibility Information 
Sheet, which will include the procedures and tests that will be paid for by the study, as well as those 
billed to the subject’s health insurer. If the subject has health insurance, they will be responsible for 
any co-pays or deductibles not covered by their insurance. 
 
9. 
Benefits 
Participants may receive an organ offer for an HCV-infected organ sooner than if they waited for an 
HCV-uninfected organ. This may have a survival benefit to the participant.  
 
10. 
Payment and Remuneration 
Study participants will receive either a parking voucher for each outpatient study visit or similar 
compensation in the form of a gift card. Total compensation for participation in the study will not 
exceed $50. 
 
11. 
Costs 
Research blood draws and study drug will be paid for by the Department of Surgery (no cost to the 
participant). All other procedures, test, and drugs are part of standard clinical care for organ 
transplantation and will be billed to the participant and/or their health insurer.  
 
 
 
12. 
References  
 
1. United Network for Organ Sharing (UNOS) Data. Accessed via https://unos.org/data/transplant-
trends. 
 
2. Gill JS, Rose C, Pereira BJ, et al. The importance of transitions between dialysis and 
transplantation in the care of end-stage renal disease patients. Kidney Int. 2007; 71(5):442. 
 
3. Danovitch GM, Cohen DJ, Weir MR, et al. Current status of kidney and pancreas transplantation 
in the United States, 1994-2003. Am J Transplant 2005; 5(4 Pt 2):904. 
 
4. Bowring MG, Kucirka LM, Massie AB, et al. Changes in utilization and discard of HCV-
antibody positive deceased-donor kidneys in the era of direct-acting antiviral therapy. 
Transplantation 2018 Dec; 102(12):2088-2095. 
 


Date: September 26, 2023 
Principal Investigator: Niraj M. Desai, MD 
Application Number: IRB00237097 
 
JHMIRB eFormA  01 
Version 3 Dated:   06/2007 
 
Page 17 of 17 
 
5. Durand CM, Bowring MG, Brown DM, et al. Direct-acting antiviral prophylaxis in kidney 
transplantation from hepatitis C virus-infected donors to noninfected recipients: an open-label 
nonrandomized trial. Ann Intern Med 2018 Apr 17; 168(8):533-540. 
 
6. Goldberg DS, Abt PL, Blumberg EA, et al. Trail of transplantation of HCV-infected kidneys into 
uninfected recipients. N Engl J Med 2017; 377(11):1105-1106. 
 
7. Gane E, Lawitz E, Pugatch D, et al. Glecaprevir and pibrentasvir in patients with HCV and 
severe renal impairment. N Engl J Med 2017; 377(15):1448-55. 
 
8. Durand CM, Barnaba B, Yu S, et al. Four-week direct-acting antiviral prophylaxis for kidney 
transplantation from hepatitis C-viremic donors for hepatitis C-negative recipients: An open-
label non-randomized study. Submitted and under review.  
 

ICF_001.pdf: 
Kidney Transplants in Hepatitis C Negative 
Recipients With Hepatitis C Viremic Donors
NCT04575896
September 29, 2020


 
Approved September 29, 2020 
Date:  September 29, 2020 
Principal Investigator:  Niraj Desai, MD 
Application No.:  IRB00237097 
 
Page 1 of 11 
Combined Parental Permission/Informed Consent/Authorization December 2018 Version 16 
 
 
 
 
 
 
 
 RESEARCH PARTICIPANT INFORMED CONSENT AND PRIVACY 
AUTHORIZATION FORM 
 
Protocol Title:  
Kidney transplants in hepatitis C negative recipients with 
hepatitis C viremic donors. An open-label, non-randomized pilot 
study to determine the safety and efficacy of two weeks of fixed-
dose glecaprevir and pibrentasvir as pre- and post-exposure 
prophylactic therapy. 
 
Application No.:            IRB00237097 
 
Supported By:  
The Johns Hopkins Department of Surgery 
 
Principal Investigator: Niraj Desai, MD 
 
Assistant Professor of Surgery 
 
720 Rutland Ave., Ross Building Room 765 
 
Baltimore, MD 21205 
 
Phone:  410-614-8297 
 
Fax: 410-367-2396 
 
 
You are being asked to join a research study. Participation in this study is voluntary.  Please read this 
consent form carefully and take your time making your decision.   Even if you decide to join now, you 
can change your mind later. 
 
1. 
Research Summary (Key Information): 
The information in this section is intended to be an introduction to the study only.  Complete details of 
the study are listed in the sections below. If you are considering participation in the study, the entire 
document should be discussed with you before you make your final decision.  You can ask questions 
about the study now and at any time in the future. 
 
The purpose of this research is to determine if giving an investigational study drug combination called 
Glecaprevir/Pibrentasvir (G/P) for 2 weeks is safe and effective in preventing the HCV virus (hepatitis C 
virus) from infecting a kidney transplant recipient when a kidney from a kidney donor with the virus is 
used for transplant.  
 
G/P belongs to a group of medications called direct-acting antiviral agents (DAAs). These drugs are 
intended to prevent the Hepatitis C Virus from multiplying and spreading in the human body. 
 
If appropriate for this study, a scanned copy of 
the signed consent form should be uploaded to 
the participant’s Epic/EMR record. 
 
 
 
 
Patient I.D. plate 


 
Approved September 29, 2020 
Date:  September 29, 2020 
Principal Investigator:  Niraj Desai, MD 
Application No.:  IRB00237097 
 
Page 2 of 11 
Combined Parental Permission/Informed Consent/Authorization December 2018 Version 16 
Approximately 10 subjects who are on the deceased donor kidney waiting list are expected to participate 
in this study at Johns Hopkins. If you decide to be in this study and are eligible, your participation will 
last up to 14 weeks. This includes a 2-week study drug administration period and a 12-week follow-up 
period. There are risks to the drug that are described later in this document. Some risks could be serious 
and not all of the side effects/risks are known.   
 
You may or may not benefit directly from being in the study and there is no payment for participation. 
 
2. 
Why is this research being done? 
This research is being done to determine if giving an investigational study drug combination called 
Glecaprevir/Pibrentasvir (G/P) for 2 weeks is safe and effective in preventing the HCV virus from 
infecting a kidney transplant recipient when a kidney from a kidney donor with the HCV is used for 
transplant.  
   
G/P belongs to a group of medications called direct-acting antiviral agents (DAAs).  These drugs are 
intended to prevent the Hepatitis C Virus from multiplying and spreading in the human body.   
 
Glecaprevir/Pibrentasvir are already approved and used for 8 weeks to treat HCV infection. The use of 
Glecaprevir/Pibrentasvir for 2 weeks in preventing HCV infection is investigational. The word 
“investigational” means that Glecaprevir/Pibrentasvir are not approved for marketing by the Food and 
Drug Administration (FDA) and are still being tested. The FDA is allowing for Glecaprevir/Pibrentasvir 
to be used in this study.  
 
Who can join this study? 
People who are 18 years or older, who are on the deceased donor kidney waiting list at Johns Hopkins 
Hospital awaiting their first or second kidney for transplant, and who have no available living donors 
may join. 
 
How many people will be in this study?  
We will enroll 10 people in this study. 
 
3. 
What will happen if you join this study? 
If you agree to be in this study, we will ask you to do the following things: 
 
Screening phase:  
Patients who are waiting for a kidney transplant at Johns Hopkins Hospital and meet the above criteria 
will be approached with this informed consent form and screened for enrollment in the study. Your 
medical record will be closely reviewed and your blood may be drawn. We will also review the 
medications you are currently taking to see if any of them should not be given with the study drug. If 
you are currently taking one of these medications and it cannot be safely discontinued or substituted 
with another medication you will not be able to continue to participate in the study and you will not be 
listed with a status of “willing to accept an HCV+ organ”. If you are prescribed any new medications 
after signing this consent, it is important that you report it to the study doctor at the time it is prescribed. 
 
Donor Identification:  
Once you provide informed consent for this study, and it has been confirmed that your medications are 
safe to give with the study drug, you will be listed in the United Network for Organ Sharing (UNOS) 
with a status of “willing to accept an HCV+ organ”. The Johns Hopkins transplant team will then 
receive HCV+ donor kidney offers for participants of this study. If an HCV+ donor is identified who 
meets the requirements of this study, you will be offered the organ. If you accept, you will become an 
active study participant. 
 


 
Approved September 29, 2020 
Date:  September 29, 2020 
Principal Investigator:  Niraj Desai, MD 
Application No.:  IRB00237097 
 
Page 3 of 11 
Combined Parental Permission/Informed Consent/Authorization December 2018 Version 16 
Active phase, transplant and study drug regimen:  
After you have signed consent and prior to you receiving a transplant we will draw approximately 9 
tablespoons of blood so we can measure how your immune system responds to getting a hepatitis C 
infected organ. If your transplant does not occur within 12 months of this blood being drawn, we may 
need to repeat the blood draw. At the time of your admission to the hospital for your transplant, you will 
undergo the standard pre-operative preparation, including laboratory testing, chest X-ray, 
electrocardiogram (EKG), and urine analysis. In addition, a blood sample for this study will be drawn. 
Your initial dose of glecaprevir and pibrentasvir will be administered by your nurse when you are called 
to the operating room.  
 
Except for the study drug, your kidney transplant and postoperative care will be the same as for patients 
not on this study. After your transplant, you will be given glecaprevir and pibrentasvir every day.  Most 
kidney transplant recipients are able to take medicine by mouth within eight hours after their transplant.  
 
Discharge from the hospital is typically between 7 and 10 days after the transplant, once your new 
kidney is functioning properly, you are tolerating a regular diet, and you have normal bowel and bladder 
function. During your hospitalization, we will discuss your medications, including glecaprevir and 
pibrentasvir, and planned follow-up visits several times.  
 
The study drug regimen phase of the study will be 2 weeks; we will monitor you closely for HCV. These 
drugs have been shown to be effective in preventing HCV complications. However, if the virus does 
become detectable, we will treat your hepatitis C according to the most current clinical standard.  
 
Follow-up: 
You will have study visits 1, 2, 4, and 12 weeks after you stop taking the study drugs. During study 
visits, we will review your medical record, complete a physical exam, and take a blood sample for the 
study. We may also ask you to come in for a visit 24 weeks after you stop taking the study drugs based 
on the results from your week 12 bloodwork. 
 
Will research test results be shared with you? 
This study may involve research tests that may produce information that could be useful for your clinical 
care. Information about your study participation will be included in your medical record and we will 
share this information with you. 
 
How long will you be in the study? 
You will be in this study for at least 14 weeks after your kidney transplant.  However, we will continue 
to collect information about your health for at least 12 months after your transplant. 
 
4. 
What happens to data and biospecimens that are collected in the study?  
Johns Hopkins and our research partners work to advance science and public health.  The data and 
biospecimens we collect from you are important to this effort. 
 
Biospecimens may include any of the following: blood, tissue, saliva, urine, bone marrow, cells, etc.  
Most biospecimens contain DNA, which is the genetic code for each person. 
 
If you join this study, you will not own the data and/or biospecimens collected from you as part of this 
research study. If researchers use them to create a new product or idea, including those that may have 
commercial value, you will not benefit financially from these efforts. 
 


 
Approved September 29, 2020 
Date:  September 29, 2020 
Principal Investigator:  Niraj Desai, MD 
Application No.:  IRB00237097 
 
Page 4 of 11 
Combined Parental Permission/Informed Consent/Authorization December 2018 Version 16 
What testing or procedures may be done with your biospecimens?  
Your biospecimens may be used for a variety of research purposes. The specific testing that is included 
in this study is taking blood samples to test for HCV plasma RNA levels and measurement of T cell 
responses to HCV peptides. Allograft biopsies will be performed if there is concern for rejection or other 
causes of graft dysfunction.  
 
How will your data and/or biospecimens be shared now and in the future?  
Sharing data and/or biospecimens is part of research and may increase what we can learn from this 
study. 
  
Often, data/biospecimen sharing is required as a condition of funding or for publishing study results.  It 
also is needed to allow other researchers to validate study findings and to come up with new ideas. 
 
Your data and/or biospecimens may be shared:  
 directly with research collaborators, other researchers, sponsors, government agencies, 
publishers of papers and other research partners  
 through government or other databases/repositories  
 
Data/biospecimen sharing could change over time, and may continue after the study ends. 
 
We will do our best to protect and maintain your data/biospecimens in a safe way.  Generally, if we 
share your data/biospecimens without identifiers (such as your name, address, and date of birth) further 
review and approval by an IRB is not needed.  However, when we share data/biospecimens, we limit the 
uses of the information and whether these data/biospecimens can be shared with another research team.  
If data/biospecimens are shared with identifiers, further IRB review and approval may be needed and the 
IRB will determine whether additional consent is required.  
 
Johns Hopkins researchers may also use the biospecimens collected in this study for future research 
purposes, which may include gene sequencing and genetic testing. Each cell contains your complete 
DNA.  Gene sequencing of your DNA provides researchers with the code to your genetic material. This 
future research may be unrelated to the current study and may include outside collaborators.  
 
Because science constantly advances, we do not yet know what future testing may include. If 
biospecimens are tested/used in ways not described above, further IRB review and approval may be 
needed and the IRB will determine whether additional consent is required. 
 
If you are not comfortable with the use of your data/biospecimens in future research, you may not want 
to participate in this study. 
 
5. 
What are the risks or discomforts of the study? 
Risks of Glecaprevir and Pibrentasvir 
The most common side effects with these study drugs are headache, tiredness, nausea, and diarrhea. In 
rare cases, there were bilirubin elevations that decreased upon completing the drug.  
 
There is a very rare possibility of acquiring hepatitis C, which may result in fulminant (sudden and 
rapidly progressing) hepatitis and death. If you develop hepatitis, the study will not be responsible for 
the cost of your treatment.  
 
 


 
Approved September 29, 2020 
Date:  September 29, 2020 
Principal Investigator:  Niraj Desai, MD 
Application No.:  IRB00237097 
 
Page 5 of 11 
Combined Parental Permission/Informed Consent/Authorization December 2018 Version 16 
Blood Draw 
Taking blood may cause discomfort, bleeding, or bruising where the needle enters the body. In rare 
cases, it may result in fainting. There is a small risk of infection. 
 
Identifiable private information  
There is the risk that information about you may become known to people outside this study.  To protect 
against this, the study information will be kept in password protected computers in locked rooms that are 
accessible only to study staff. 
 
Unknown risk  
There may be side effects and discomforts that are not yet known.   
 
6. 
Are there risks related to pregnancy? 
To date there is no adequate human data available to establish whether or not the study drug poses a risk 
to an embryo or fetus. 
 
For female participants, extreme care must be taken to avoid pregnancy during this study and for up to 6 
months after the last dose of glecaprevir and pibrentasvir. For male participants, extreme care must be 
taken to avoid pregnancy in female partners during this study and for up to 6 months following 
completion of the study regimen. If you are pregnant, intending to become pregnant, or currently nursing 
(breastfeeding) a child, you cannot be in this study. If you are a man whose partner is currently pregnant 
or wishing to become pregnant, you cannot be in this study.  
 
You must protect yourself or your partner from becoming pregnant before, during, and after the study. 
Women, and men with female partners capable of becoming pregnant, must use effective methods of 
birth control as described below. Your study doctor will need to document what type(s) of birth control 
you are using. 
 
Women only:  
Women who can get pregnant should not take study drug(s) unless they and their partner do not have 
intercourse ever or are using 2 methods of birth control for the duration of the study (starting 3 weeks 
prior to the Day 1 visit) and for a minimum of 6 months after last dose of study drug or longer as 
directed by your study doctor. 
 
At least one method of birth control must be a condom used correctly by your male partner. Your study 
doctor will discuss with you other methods of birth control that can be used in combination with a 
condom.  
 
Women who can get pregnant must have a negative pregnancy test at time of admission for transplant, 
and prior to taking the first dose of study drug.  
 
You must tell your study doctor immediately if you become pregnant while in this study and for 6 
months after stopping the study drug, or for as long as you have been directed by your study doctor to 
use contraception. The study doctor will tell you about the possible risks to the embryo or fetus and 
options available to you.  
 
In the event of a positive urine pregnancy result, you will be instructed to return to the study clinic as 
soon as possible for a serum (blood) pregnancy test.  
 


 
Approved September 29, 2020 
Date:  September 29, 2020 
Principal Investigator:  Niraj Desai, MD 
Application No.:  IRB00237097 
 
Page 6 of 11 
Combined Parental Permission/Informed Consent/Authorization December 2018 Version 16 
Men only:  
If you have a female partner who cannot become pregnant, you must still consistently and correctly use 
a condom.  
 
If you have a female partner who can become pregnant, you and your partner must use two forms of 
birth control for the entire study and for a minimum of 6 months after the last dose of study drug.  You 
must use a condom while your female partner uses 1 other method of birth control. Your study doctor 
will discuss with you other methods of birth control that can be used in combination with a condom.  
 
If your female sex partner becomes pregnant while you are in the study or within 6 months after your 
last dose of study drug, it is unknown if the study drug will do harm to an embryo or fetus. If you have a 
female partner who becomes pregnant or suspects that she has become pregnant while you are in the 
study or within 6 months after your last dose of study drug, you will be required to notify your study 
doctor immediately.  
 
As the risks to your partner and the embryo or fetus are not known, it is recommended for your partner 
to receive appropriate prenatal care. Your study doctor may need to disclose to your partner details of 
this study and your taking part in it.  
 
Male participants must also agree not to donate sperm from the time you first take your first dose of 
study drug until 6 months after the last dose of study drug  
 
Please note: Hormonal birth control may be more effective when taken for at least 3 months. Even if you 
and your female partner use a medically proven birth control method, you could still cause your partner 
to become pregnant. 
 
Please share this information with your partner.  
 
7. 
Are there benefits to being in the study? 
You may or may not directly benefit from this study. In some cases patients that are willing to accept an 
organ from an HCV-infected donor will receive an organ offer sooner than if they were not willing to 
accept. This may or may not have a survival benefit to being on or staying on dialysis. If you take part in 
this study, you may help others in the future.   
 
8. 
What are your options if you do not want to be in the study? 
You may or may not directly benefit from this study. In some cases patients that are willing to accept an 
organ from an HCV-infected donor will receive an organ offer sooner than if they were not willing to 
accept. This may or may not have a survival benefit to being on or staying on dialysis. If you take part in 
this study, you may help others in the future.  
 
You do not have to join this study. Other options include waiting for an organ from a non-infected 
donor. If you do not join, your care at Johns Hopkins will not be affected.  
 
9. 
Will it cost you anything to be in this study?   
You will receive a separate Insurance and Research Participant Financial Responsibility Information 
Sheet.  
 
This Sheet will give you the following information: 


 
Approved September 29, 2020 
Date:  September 29, 2020 
Principal Investigator:  Niraj Desai, MD 
Application No.:  IRB00237097 
 
Page 7 of 11 
Combined Parental Permission/Informed Consent/Authorization December 2018 Version 16 
 The procedures, tests, drugs or devices that are part of this research and that will be paid for by 
the study (no cost to you).   
 The procedures, tests, drugs or devices that will be billed to you and/or your health insurer.  If 
you have health insurance, you will be responsible for any co-pays or deductibles not covered by 
your insurance.  
 
10. 
Will you be paid if you join this study? 
No. However, you will receive a parking pass at time of transplant and each post-transplant study visit. 
 
11. 
Can you leave the study early? 
 You can agree to be in the study now and change your mind later. 
 If you wish to stop, please tell us right away. 
 Leaving this study early will not stop you from getting regular medical care.  
  
 
If you leave the study early, Johns Hopkins may use or share your health information that it has already 
collected if the information is needed for this study or any follow-up activities.  
 
12. 
Why might we take you out of the study early?  
You may be taken out of the study if: 
 Staying in the study would be harmful. 
 You need treatment not allowed in the study. 
 You fail to follow instructions. 
 You become pregnant. 
 The study is cancelled. 
 There may be other reasons to take you out of the study that we do not know at this time.  
 
If you are taken out of the study early, Johns Hopkins may use or give out your health information that it 
has already collected if the information is needed for this study or any follow-up activities. 
 
13. 
How will your privacy be maintained and how will the confidentiality of your data 
be protected?  
 
HIPAA Authorization for Disclosure of Protected Health Information  
 
What information is being collected, used, or shared? 
To do this research, we will need to collect, use, and share your private health information.  By signing 
this document, you agree that your health care providers (including both Johns Hopkins Medicine and 
others) may release your private health information to us, and that we may use any and all of your 
information that the study team believes it needs to conduct the study.  Your private information may 
include things learned from the procedures described in this consent form, as well as information from 
your medical record (which may include information such as HIV status, drug, alcohol or STD 
treatment, genetic test results, or mental health treatment). 
 
Who will see, use or share the information?  
The people who may request, receive, or use your private health information include the researchers and 
their staff.  Additionally, we may share your information with other people at Johns Hopkins, for example 
if needed for your clinical care or study oversight.  To improve coordination of your research and clinical 
care, some information about the study you join will be included in your electronic medical record.   


 
Approved September 29, 2020 
Date:  September 29, 2020 
Principal Investigator:  Niraj Desai, MD 
Application No.:  IRB00237097 
 
Page 8 of 11 
Combined Parental Permission/Informed Consent/Authorization December 2018 Version 16 
By signing this form, you give permission to the research team to share your information with others 
outside of Johns Hopkins.  This may include the sponsor of the study and its agents or contractors, 
outside providers, study safety monitors, government agencies, other sites in the study, data managers 
and other agents and contractors used by the study team.   
 
We try to make sure that everyone who sees your information keeps it confidential, but we cannot 
guarantee that your information will not be shared with others.  If your information is disclosed by your 
health care providers or the research team to others, federal and state confidentiality laws may no longer 
protect it.   
 
Do you have to sign this Authorization? 
You do not have to sign this Authorization, but if you do not, you may not join the study. 
 
How long will your information be used or shared?  
Your Authorization for the collection, use, and sharing of your information does not expire. 
Additionally, you agree that your information may be used for similar or related future research studies. 
 
What if you change your mind? 
You may change your mind and cancel this Authorization at any time.  If you cancel, you must contact 
the Principal Investigator in writing to let them know by using the contact information provided in this 
consent form.  Your cancellation will not affect information already collected in the study, or information 
that has already been shared with others before you cancelled your authorization. 
 
How will your information be protected? 
There is the risk that information about you may become known to people outside this study. To protect 
against this, all samples will be stored using a de-identified label that does not contain personal 
identifiers. Any collected data will also be de-identified and labeled with a code and the key to the code 
will be kept in a password-protected computer at Johns Hopkins that will only be accessible to the 
study’s investigators and research staff. 
 
14. 
Will the study require any of your other health care providers to share your health 
information with the researchers of this study? 
As a part of this study, the researchers may ask to see your health care records from your other health 
care providers. You will be asked to give us a list of other health care providers that you use.  
 
15. 
What treatment costs will be paid if you are injured in this study? 
Johns Hopkins does not have a program to pay you if you are hurt or have other bad results from being 
in the study. However, medical care at Johns Hopkins is open to you as it is to all sick or injured people.   
 
The costs for any treatment or hospital care you receive as the result of a study-related injury that are not 
covered by a health insurer will be billed to you. 
 
By signing this form, you will not give up any rights you have to seek compensation for injury. 
 
16. 
What other things should you know about this research study? 
During the study, we will tell you if we learn any new information that might affect whether you wish to 
continue to participate. 
 


 
Approved September 29, 2020 
Date:  September 29, 2020 
Principal Investigator:  Niraj Desai, MD 
Application No.:  IRB00237097 
 
Page 9 of 11 
Combined Parental Permission/Informed Consent/Authorization December 2018 Version 16 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. 
Law.  This Web site will not include information that can identify you. At most, the Web site will 
include a summary of the results. You can search this Web site at any time. If you would like to review 
the information for this study, or a summary of the results, ask the study team doctor for the 
ClinicalTrials.gov study registration number. 
 
What is the Institutional Review Board (IRB) and how does it protect you?  
This study has been reviewed by an Institutional Review Board (IRB), a group of people that reviews 
human research studies. The IRB can help you if you have questions about your rights as a research 
participant or if you have other questions, concerns or complaints about this research study.  You may 
contact the IRB at 410-502-2092 or jhmeirb@jhmi.edu.   
 
What should you do if you have questions about the study, or are injured or ill as a result of being 
in this study?  
Call the principal investigator, Dr. Niraj Desai at 410-614-8297.  If you wish, you may contact the 
principal investigator by letter. The address is on page one of this consent form. If you cannot reach the 
principal investigator or wish to talk to someone else, call the IRB office at 410-502-2092.   
 
If you have an urgent medical problem or think you are injured or ill because of this study, call 911 or 
go to your local emergency department.  You should also call Dr. Niraj Desai at 410-614-8297 during 
regular office hours and at 314-392-7743 after hours and on weekends. If this doctor is not available, the 
operator will page the “on call physician.” 
 
17. Optional Study Components: 
This part of the consent form is about optional component(s) of the study that you can choose to take 
part in or not. You can still take part in the main study even if you say “no” to this/these optional 
component(s).  
 
Future Contact 
We would like your permission for our research team to contact you in the future.  Please note that your 
decision below does not prevent other researchers at Johns Hopkins from contacting you about other 
research. 
 
Please sign and date your choice below: 
 
YES    ________________________  
 
______________ 
Signature of Participant 
 
 
Date 
 
NO     ________________________ 
 
______________ 
Signature of Participant 
 
 
Date 
 
 
 


 
Approved September 29, 2020 
Date:  September 29, 2020 
Principal Investigator:  Niraj Desai, MD 
Application No.:  IRB00237097 
 
Page 10 of 11 
Combined Parental Permission/Informed Consent/Authorization December 2018 Version 16 
18. 
What does your signature on this consent form mean?  
Your signature on this form means that you have reviewed the information in this form, you have had a 
chance to ask questions, and you agree to join the study. You will not give up any legal rights by signing 
this consent form.  
 
WE WILL GIVE YOU A COPY OF THIS SIGNED AND DATED CONSENT FORM 
 
 
 
________________________________________________________________________________________________________________________ 
Signature of Participant  
 
 
 
 
 
(Print Name)  
 
 
 
Date/Time  
 
 
 
________________________________________________________________________________________________________________________ 
Signature of Person Obtaining Consent  
 
 
 
(Print Name)  
 
 
 
Date/Time 
 
 
 
________________________________________________________________________________________________________________________ 
Signature of Interpreter/Witness to Consent Procedures  
 
 
(Print Name) 
 
 
 
Date/Time 
(Required for studies enrolling non-English speakers using the short form process or otherwise as determined required by the IRB) 
 
I have received the separate Insurance and Research Participant Financial Responsibility Information Sheet.   
 
 
________________________________________________________________________________________________________________________ 
Signature of Participant, LAR or Parent/Guardian  
 
 
(Print Name) 
 
 
 
Date/Time 
 
NOTE: A COPY OF THE SIGNED, DATED CONSENT FORM MUST BE KEPT BY THE PRINCIPAL INVESTIGATOR AND A COPY 
MUST BE GIVEN TO THE PARTICIPANT.  IF APPROPRIATE FOR THIS STUDY, A SCANNED COPY OF THE SIGNED CONSENT 
FORM SHOULD BE UPLOADED TO THE PARTICIPANT’S EPIC/EMR RECORD (UNLESS NO MEDICAL RECORD EXISTS OR 
WILL BE CREATED).  
 
 
 


 
Approved September 29, 2020 
Date:  September 29, 2020 
Principal Investigator:  Niraj Desai, MD 
Application No.:  IRB00237097 
 
Page 11 of 11 
Combined Parental Permission/Informed Consent/Authorization December 2018 Version 16 
DOCUMENTATION OF PHYSICIAN/MID-LEVEL PROVIDER CONSENT 
 
My signature below indicates that I have discussed the risks, benefits, and alternatives, answered any 
questions, and believe the participant is able to make an informed choice to join the study. 
 
 
 
________________________________________________________________________________________________________________________ 
Signature of Physician/Mid-Level Provider  
 
 
 
(Print Name)  
 
 
 
Date/Time 
 
 
_______________________________________________________________________________________________________________________
Signature of Participant   
 
 
 
 
 
(Print Name)  
 
 
 
Date/Time 
 
 
 
________________________________________________________________________________________________________________________ 
Signature of Interpreter/Witness to Consent Procedures       
 
(Print Name)  
 
 
 
Date/Time 
(Required for studies enrolling non-English speakers using the short form process or otherwise as determined required by the IRB) 
 
 
 
NOTE: A COPY OF THE SIGNED, DATED CONSENT FORM MUST BE KEPT BY THE PRINCIPAL INVESTIGATOR AND A COPY 
MUST BE GIVEN TO THE PARTICIPANT.  IF APPROPRIATE FOR THIS STUDY, A SCANNED COPY OF THE SIGNED CONSENT 
FORM SHOULD BE UPLOADED TO THE PARTICIPANT’S EPIC/EMR RECORD (UNLESS NO MEDICAL RECORD EXISTS OR 
WILL BE CREATED).