Clinical trial NCT04515797
Conditions: Kidney Failure Hepatitis C Kidney Disease, Chronic
Keywords: Kidney Transplant Kidney Failure HCV Hepatitis C
Sponsor: Massachusetts General Hospital
Start date: 2021-05-01; Completion date: 2023-08-31
Enrollment: 2 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This is a single center study characterizing the experience of administration of 4 weeks of pan-genotypic DAA therapy in kidney transplantation to prevent the transmission of hepatitis C virus infection from an HCV-positive donor kidney to an HCV-negative recipient.

Detailed description:
The goal of this study is to determine if the administration of glecaprevir and pibrentasvir (G/P) for 4 weeks beginning in the immediate peri-transplant period prevents establishment of HCV infection in HCV negative recipients receiving transplanted kidneys from HCV RNA positive donors.

Arms: arm 1: 4 week treatment period with glecaprevir and pibrentasvir (G/P) within 24 hours of transplant
Interventions: intervention 1: Glecaprevir and Pibrentasvir
Intervention descriptions: intervention 1: 4 weeks of treatment starting within 24 hrs of kidney transplant

Protocol documents:
Prot_SAP_000.pdf: 
AbbVie Investigator-Initiated Studies (IIS): Required Protocol Components 
 
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Version: 5.0, December 16, 2022 
Section 
 
1.0 
 General Information 
1.1 
Study Title: 
QUICKly eradicate Hepatitis C in patients Undergoing REnal Transplant with 4 weeks of 
Glecaprevir/Pibrentasvir (QUICK-CURE) 
1.2 
1.2 Institution 
Name: 
Massachusetts General Hospital, Boston, MA 02114 
1.3 
Investigator 
Contact 
Information: 
Nahel Elias 
Transplant Surgery, Massachusetts General Hospital 
55 Fruit Street 
Boston, MA, 02114 
Phone:  617-726-5277 
E-mail: Elias.Nahel@mgh.harvard.edu  
 
Raymond T. Chung 
Gastrointestinal Unit, Massachusetts General Hospital 
55 Fruit Street 
Boston, MA, 02114 
Phone:  617-643-2257 
Mobile: 
 
E-mail: chung.raymond@mgh.harvard.edu 
 
Meghan Sise, MD, MS 
Division of Nephrology, Massachusetts General Hospital 
165 Cambridge St. Suite 302 
Boston, MA 02114 
Phone: 617-643-3948 
Mobile: 
 
Email: msise@partners.org 
 
2.0 
Background Information 
2.1 
Rationale & 
Background 
Information 
Nearly 95,000 people in the United States are waiting for a kidney transplant. Increasing kidney 
transplantation is an important component of the Advancing American Kidney Health Initiative, 
and identifying ways to decrease discard of potentially viable kidneys is an important priority. Over 
the last five years, the number of deceased organ donors with hepatitis C virus (HCV) infection has 
increased substantially, largely due to the opioid epidemic. Since HCV-infected donors are 
typically younger and their kidneys are predicted to have robust allograft function, there has been 
tremendous interest in increasing utilization of kidneys from these donors by allowing recipients 
who do not have HCV to accept offers from HCV-infected donors, and then begin treatment with 
direct-acting antiviral therapies (DAAs). These strategies are only possible because DAAs are 
highly effective at curing HCV with relatively short courses and are well tolerated with very few 
side effects. Single center clinical trials investigating whether transplantation from actively viremic 
HCV-infected donors to HCV-naïve recipients have demonstrated 100% cure rates using a 12-
week course of DAAs begun in the peri-transplant period. However, other single-center 
retrospective studies have delayed starting DAA therapy for weeks to months after kidney 
transplant due in part to difficulties in insurance approval. These studies reported higher rates of 
complications, including virologic relapses, episodes of acute rejection, cytomegalovirus infection, 
polyoma virus infection, and even cases of fibrosing cholestatic hepatitis. We recently completed 
enrollment for the MYTHIC trial, a multicenter, prospective, open-label study to evaluate the 
safety, efficacy, and viral kinetics when glecaprevir and pibrentasvir (G/P), a fixed-dose 


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combination antiviral regimen, was administered on post-operative day three and continued for 
eight weeks after transplantation from an HCV-viremic donor to an HCV-naïve recipient. Because 
of the efficacy of G/P and the low viral loads observed after kidney transplant, many have 
wondered whether shorter courses of G/P could be effective, particularly if G/P is begun in the 
immediate post-transplant period, before HCV infection can become established. Pilot studies have 
examined four-week courses of G/P and demonstrated so far 100% cure rates however numbers are 
very small. The American Society of Transplantation Consensus Conference on the Use of HCV 
Donors in Solid Organ Transplantation has highlighted the urgent need for more prospective 
investigation into the risks and benefits of using organs from HCV-infected donors. Indeed, more 
prospective studies will be needed to determine the safety of these approaches. However, we 
believe that starting G/P in the peri-transplant period compared to waiting until viremia is 
established in the recipient will minimize post-transplant complications and be highly cost 
effective. 
 
3.0 
Core Protocol 
3.1 
Study 
Objectives 
and Purpose 
Primary Study Objective 
Determine if the administration of G/P for 4 weeks beginning in the immediate peri-transplant 
period prevents establishment of HCV infection in HCV negative recipients receiving transplanted 
kidneys from HCV RNA positive donors 
 
Secondary Objectives  
1. Evaluate the safety and tolerability of G/P in patients undergoing kidney transplantation by 
evaluating study-participation related (either related to G/P or HCV-viremia) severe and non-severe 
events from transplant until one-year post-transplant. Post-transplant allograft function outcomes: 
mean eGFR over time through the 1-year study period. We will also determine the rate of the 
following clinical outcomes related to safety: death, graft failure, acute allograft rejection, delayed 
graft function, ALT elevations > 5x ULN that occur within the 1-year study period 
 
2. Capture patient reported outcomes 1 year after transplant or 1 year after consent (for those who 
remain on the waiting list) using the Functional Assessment of Chronic Illness Therapy Fatigue 
Subscale (FACIT-F) and compare results among patients who receive a kidney from a HCV-
viremic donor and those who do not. 
 
Hypothesis 
We hypothesize that the administration of G/P (300mg/120mg) once daily for 4 weeks beginning 
within 24 hours of kidney transplant (either on-call to the operating room or within 24 hours of 
transplant) will prevent detectable HCV RNA in HCV RNA negative recipients receiving 
transplanted kidneys from HCV RNA positive donors during and after treatment completion. 
 


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3.2 
Study Design 
This study is an open label, single-center, interventional, uncontrolled, pragmatic clinical trial for 
the donation of HCV positive kidneys to HCV negative patients with ESRD. It is a single arm 
study; all HCV-uninfected recipients of an HCV-viremic kidney transplant will begin G/P for 4 
weeks beginning in the peri-transplant period (either on-call to the operating room or within 24 
hours of transplant). Forty subjects will be enrolled (transplanted and dosed with G/P), with up to 
80 total consented to determine eligibility. The target population is patients with ESRD who are at 
least 18 years old, do not have history of HCV infection, and are listed for transplant at the MGH 
Transplant Center. 
 
Primary Endpoints 
SVR12 - sustained virologic response 12 weeks after completing G/P (16 weeks post-kidney 
transplant). 
 
Secondary Endpoints 
• 
Severe and non-severe adverse events attributed to study drug  
• 
Severe and non-severe adverse events attributed to HCV-viremia  
• 
Assessment of HCV RNA viral load at on-treatment visits (week 2 and 4) 
• 
Post-transplant allograft function outcomes: mean eGFR over time through the 1-year 
study period.  
• 
The rate of the following clinical safety outcomes: death, graft failure, acute allograft 
rejection, delayed graft function, ALT elevations > 5x ULN that occur within the 1-year 
study period. We will classify which of these events are related to G/P or HCV-Viremia 
and those which are not related.  
 
3.3 
Inclusion 
Criteria 
Donor Inclusion Criteria:  
a. Detectable HCV NAT test  
b. KDPI score is less than ≤ 0.850  
c. Traditional Donor Selection Criteria Met - acceptable for transplantation per usual 
evaluation  
 
Recipient Inclusion Criteria:  
a. Met MGH Transplant Center criteria and already listed for kidney transplant with stage 5 
CKD / ESRD (eGFR <15 ml/min/1.73m2 or on renal replacement therapy) 
b. Must agree to birth control. Women must agree to use birth control in accordance with 
Mycophenolate Risk Evaluation and Mitigation Strategy and at least one barrier method  
c. No evidence of clinically significant liver disease at the time of transplant readiness as 
determined by the clinical team  
d. Able to sign informed consent 
 


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3.4 
Exclusion 
Criteria 
Donor Exclusion Criteria:  
a. Confirmed HIV  
b. Confirmed HBV positive (surface antigen or HBV DNA positive)  
c. Any standard contra-indication to donation noted in donor (significant malignancy, unusual 
infection, kidney anatomical damage or significant pathology)  
 
Recipient Exclusion Criteria:  
a. Pregnant or nursing (lactating) women  
b. HBV positivity (Ag or DNA)  
c. Any contra-indication to kidney transplantation per MGH transplant center protocol 
d. Any signs or symptoms of clinically significant chronic liver disease per transplant center 
physician 
e. Inability to discontinue any medication with a known drug-drug interaction as listed in the 
G/P package insert 
 
 
3.5 
Study Flowchart 
 
Visit 
AEs 
Con 
Meds 
G/P 
adherence 
Vitals & 
PE 
Dispense 
G/P 
CMP 
CBC 
& 
diff 
HCV 
RNA 
HCV 
Ab 
HCG 
DAA 
resistance 
PROMs 
Screening 
 
x 
 
x 
 
x 
x 
x 
x 
x 
 
 
Peri-transplant visit 
x 
x 
 
x 
 
x 
x 
 
 
 
 
 
Day 1 post-KT 
x 
x 
 
x 
x 
x 
x 
x 
 
 
 
 
Week 2 post-KT 
x 
x 
X 
x 
 
x 
x 
x 
 
 
 
 
Week 4 post-KT 
x 
x 
x 
x 
 
x 
x 
x 
 
 
 
 
End of G/P 
x 
x 
x 
 
 
 
 
 
 
 
 
 
Post-treatment 
Week 4 
x 
x 
 
x 
 
x 
x 
x 
 
 
 
 
Post-treatment 
Week 12 
x 
x 
 
 
 
x 
x 
x 
 
 
 
 
Post-treatment 1 
Year 
x 
x 
 
x 
 
x 
x 
x 
x 
 
 
x 
G/P treatment 
failure 
x 
 
 
 
 
 
 
x 
 
 
x 
 
Premature 
discontinuation 
x 
 
 
x 
 
x 
x 
x 
 
 
 
 
1 year from 
consent (if not 
transplanted) 
 
 
 
 
 
 
 
 
 
 
 
x 
 
 


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3.6 
Study 
Procedures 
The study will be a single-arm, open-label, pragmatic trial to evaluate the efficacy and safety of 
fixed-dose combination tablets of glecaprevir/pibrentasvir (G/P) for four weeks in HCV-negative 
subjects who consent to receive a kidney transplant from an HCV RNA-positive deceased kidney 
donor. 
 
Patient reported outcomes will be performed 1 year after transplant or 1 year after consent for those 
who do not undergo transplant.  
 
Screening Period 
Potential subjects will be contacted by a member of the research staff to provide information about 
the study and to gauge interest. Interested individuals will be provided educational materials on 
HCV infection and transplantation. After this, potential subjects will be eligible for screening (there 
should be at least 24 hours between the educational visit and the screening visit, though special 
cases may allow these visits to occur on the same day as educational materials were provided). At 
the screening visit, the potential subject will review the informed consent again with the PI and 
sign if still interested in participating. Upon signing consent, the individual will receive a unique 
subject number. Both in-person and remote written informed consent will be conducted in 
accordance with institutional policy. Remote consent can be performed by a physician investigator 
in lieu of in person consent. During the consent process, the consenting physician will explain the 
scope of the study, potential risks and benefits. When the subject fully understands the scope of 
study participation, their consent will be obtained. Consents will be signed by the patient and 
mailed back to the study site, at which time the consenting physician will sign the consent. The rest 
of the screening visit will include a physical exam, vital signs, blood tests, and review of medical 
history and concomitant medications. The study investigators and research team will then review 
the potential subject’s information to determine whether the patient is eligible to participate or not. 
Patients who are on contraindicated medications will need to be able to cease the contraindicated 
medication or switch to an alternative, allowed co-medication to be deemed eligible. Up to 80 
subjects will be consented for trial participation, of whom 40 subjects will receive an HCV RNA-
positive kidney and open-label G/P for 4 weeks post-transplant.  
 
Waitlist Period 
Subjects who have been enrolled in the study and are listed for kidney transplant at MGH 
Transplant Center will be placed in the waitlist group until being called for a transplant. While on 
the waitlist, subjects will be monitored by the transplant team for changes to health status, and 
changes in transplant waitlist status as per standard of care. 
 
Baseline Period 
Upon matching to a donor, the study subject will come into the hospital, following kidney 
transplantation standard-of-care procedures. The first dose of G/P will be given as early as "on call" 
to the operating room and no later than 24 hours after the transplant operation begins. The patient 
will be provided with a month supply of drug upon discharge from hospital. Treatment with G/P 
will then continue once daily for four weeks. Physical exam, vital signs, CMP, CBC & differential 
and pregnancy test will occur at baseline per standard of care. 
 
On-treatment Period 
Subjects will be followed per standard of care throughout the on-treatment period. Data will be 
recorded on day 1, week 2, and week 4 post-transplant: adverse events (including graft survival, 
mortality, allograft rejection, and potential hepatic and extrahepatic manifestations of HCV 
infection), concomitant medications, adherence to G/P dosing, vitals, physical exam, CMP, CBC & 
differential, HCV RNA will take place at these visits. Counseling regarding contraception and 


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pregnancy testing will occur per standard of care.  
 
Follow-up Period 
Subjects will be followed per standard of care throughout the post-treatment period up to one-year 
post-transplant. Data will be recorded on week 4 and week 12 post-treatment and week 52 post-
transplant: adverse events (including graft survival, mortality, allograft rejection, and potential 
hepatic and extrahepatic manifestations of HCV infection), concomitant medications, adherence to 
G/P dosing, vitals, physical exam, CMP, CBC & differential, HCV RNA and pregnancy test, as per 
standard of care. Recipients of RNA-positive kidneys will be assessed for SVR12 at the week12 
post-treatment visit. HCV Ab will be tested at screening and 1 year after transplant. Subjects 
treated with G/P who experience virologic failure will be evaluated for the emergence/persistence 
of direct-acting antiviral agent (DAA)-resistant viral variants, and suitable retreatment will be 
offered to study participants directed by Dr. Chung or Dr. Sise. Patients will receive a standard of 
care kidney transplant care including induction and maintenance immunosuppression as directed by 
their treating transplant team. 
 
Subject Withdrawal Criteria 
Pre-transplant patients (still on the waiting list) will be withdrawn if he or she has not achieved 
MGH Transplant Center criteria (per inclusion criteria). The patient will be removed from the study 
and will not be followed-up any longer. 
 
Study subjects have the right to withdraw from the study at any time. Additionally, the investigator 
may decide to withdraw a subject from the study at any time, if the investigator considers it 
necessary for any reason (including adverse event or failure to comply with protocol). 
 
If the subject withdraws from the study post-transplant while on treatment with G/P, an Early 
Discontinuation visit should occur as soon as possible. At this visit, the following procedures will 
occur: physical exam, vital signs, CMP, CBC & differential, and HCV RNA. The subject will be 
treated according to the principal investigator's best clinical judgment. The last dose of the study 
drug and reason for discontinuation will be recorded in the medical record and submitted to the 
sponsor and IRB for review. The subject should then be followed for up to 24 weeks post-
transplant to monitor for HCV RNA. 
 
If the subject withdraws from the study with an ongoing adverse event or an unresolved laboratory 
result that is significantly outside of the reference range, the investigator will attempt to provide 
follow-up until a satisfactory clinical resolution of the laboratory result or adverse event is 
achieved. 
 
Study subjects with treatment failure, as defined below, will be provided a regimen chosen at the 
discretion of study’s principal investigator (Raymond Chung, MD or Meghan Sise, MD). The 
retreatment of the subject will then be followed per standard of care. Retreatment will be handled 
outside of this protocol, at the discretion of the treating physician, coordinating with best practices 
recommendations from the principal investigator. The treating team will apply for coverage of the 
second-line DAAs through insurance since at that point the infection will be established. Hospital 
funds have been made available to cover any case where insurance fails to approve DAAs after 
transplant or an uninsured patient does not meet the institution’s criteria for indigent status, so if 
the patient’s insurance does not cover second-line DAA or an uninsured patient does not meet the 
institution’s criteria for indigent status we will use the hospital funds to assure retreatment. 
Study Record Retention 


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Study records will be maintained at the study site for a minimum of 7 years after the study has 
completed (LSLV) 
3.7 
Statistical 
Analysis and 
Sample Size 
Justification 
Sample Size Justification 
Power/Sample Size: This study is designed to generate preliminary data related to cure rates 
(defined as SVR12) from treating donor-derived HCV infection post kidney transplantation using 4 
weeks of G/P. For this reason, the sample size was not determined with reference to power to 
detect differences between groups for the primary objective. The lower bound of a one-sided 95% 
confidence interval will be performed using the Clopper pearson exact method.  
 
This is a pilot study with the goal to complete enrollment in 18 months. 40 patients will be dosed 
with medication. With 40 patients, if 40/40 are cured the lower bound of the confidence interval 
will be > 92%.   
 
Statistical Analysis Plans 
Include statistical methods for analysis of all primary and secondary endpoints 
Variables/Time Points of Interest. The primary variable of interest will be HCV RNA at the 
multiple time-points assessed during and after treatment. The primary efficacy outcome 
“Prevention of HCV Transmission” will be determined by a negative HCV RNA test at 12 weeks 
after completing G/P. A summary of reasons for SVR12 non-response (e.g., establishment of 
infection, loss to follow-up, or other) will be provided. We will use an intention to treat analysis to 
determine, but will also modified intention to treat which only evaluates virologic failures. The 
safety outcomes include summation of treatment related-severe and non-severe adverse events. We 
will only collect data on adverse events deemed to be at possibly related to study participation 
(either from the study treatment G/P or from HCV viremia itself). An adverse event will be 
considered treatment-emergent if it begins or worsens in severity after initiation of study drug 
through 30 days post-study drug dosing. Related adverse events are those considered at least 
possibly related to study. The number and percentage of subjects with the following clinical 
outcomes and data post-transplant as applicable: death, graft failure, acute allograft rejection, 
delayed graft function, ALT elevations > 5x ULN, and SAEs. Statistical Methods Patient 
characteristics for this transplanted cohort (N=40) will be presented with summary statistics for 
baseline demographics and clinical variables. The SVR12 rate will be presented and 95% CI 
constructed with the exact test. Mean and standard deviation for on-treatment laboratory values 
will be presented to analyze safety. Power/Sample Size: This study is designed to generate 
preliminary data related to cure rates (defined as SVR12) from treating donor-derived HCV 
infection post kidney transplantation using 4 weeks of G/P. For this reason, the sample size was not 
determined with reference to power to detect differences between groups for the primary objective. 
The lower bound of a one-sided 95% confidence interval will be performed using the Wilson’s 
score method.  


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The primary efficacy endpoint is sustained virologic response 12 weeks post dosing (SVR12), 
defined as HCV RNA < LLOQ 12 weeks after the last actual dose of G/P. The SVR12 rate will be 
determined from all enrolled subjects who received an HCV RNA-positive kidney and received at 
least one dose of G/P study drug along with a two-sided 95% confidence interval. The confidence 
interval for the SVR 12 rate will be calculated using Clopper pearson exact method. 
 
As an exploratory secondary outcome, we will compare FACIT-F scores among three groups 1. 
HCV-viremic donor kidney transplant recipients 2. Standard of care kidney transplant recipients 3. 
Patients remaining on the kidney transplant waiting list. Means will be compared using ANOVA 
testing.  
 
Investigators will be responsible for analyzing data with statistical support. 
 
3.8 
Specific Drug 
Supply 
Requirements 
The investigator and research team will keep accurate records of the study drug (G/P 100 mg/40 
mg). The study drug will be stored at 15° to 25°C (59° to 77°F) in the Clinical Trials Research 
Pharmacy (CTP) at MGH. It will be maintained under adequate security and stored under the 
conditions specified on the label until dispensed for subject use, destroyed on-site, or returned to 
AbbVie (or designee) as per ICH/GCP Guidelines, local regulations and MGH institutional 
policies. 
 
The investigator and research team will also maintain a current disposition record of study drug 
(inventoried and dispensed) at the study site, including: 
• 
amount received and placed in storage area 
• 
amount currently in storage area 
• 
label identification number or batch number 
• 
amount dispensed to and returned by each subject, including unique subject identifiers 
• 
amount destroyed at study site, if applicable 
• 
amount returned to AbbVie, if applicable 
• 
dates and initials of person responsible for Investigational Product dispensing/ 
accountability, as per the Delegation of Authority Form 
  
3.9 
Safety 
Reporting 
Subjects will be monitored throughout the study period for clinical and laboratory evidence of 
adverse events, according to standard medical practice, AASLD HCV guidelines, and kidney 
transplant protocols. An adverse event is defined as any untoward medical occurrence associated 
with the protocol procedures, whether or not drug or procedure related. This is considered to be any 
sign, symptom, illness, or experience that develops or worsens during the course of the study. 
Every adverse event will be reviewed by the principal investigator for adjudication on relatedness 
to study protocol. Only adverse events that are related to study participation will be reported. We 
consider study participation to be related to G/P or receiving an HCV + kidney transplant. Not 
those related to kidney transplant, immunosuppression, underlying disease process etc. Adverse 
event logs will be kept for each subject enrolled in the study and provided to the sponsor and IRB 
for review. 
 
A Data Safety Monitoring Committee (DSMC) will be established to review subject data after 
every 10 transplants and on an ad hoc basis. The DSMC is comprised of three physicians who have 
expertise in transplantation, infectious diseases, and hepatology. The DSMC will review all safety 
data including adverse events and make determinations regarding the conduct and continuation of 
the study. 


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If an adverse event meets the following criteria, it will be reported to the sponsor (AbbVie) as a 
serious adverse event (SAE) within 24 hours of learning of the event, regardless of relationship to 
study drug or procedures: 
• 
Death of subject 
• 
Life threatening: per investigator, an event that would have resulted in immediate fatality 
had medical intervention not been taken 
• 
Hospitalization or prolongation of hospitalization (does not include emergency room visit 
or admission to outpatient facility) 
• 
Persistent or significant disability/incapacity: event that results in condition that 
significantly interferes with daily activities of subject 
• 
Important medical event requiring medical or surgical intervention to prevent serious 
outcome: per investigator, an event that may lead to one of the outcomes listed above and 
therefore requires medical or surgical intervention 
• 
Pregnancy that has resulted in congenital anomaly: An anomaly detected at or after birth, 
or any anomaly that results in fetal loss.” 
SAEs will be categorized as pre-transplant or post-transplant, and pre-treatment, on-treatment, or 
post-treatment. The following information will be reported to the sponsor and to the IRB: 
• 
Admission and discharge notes 
• 
Consults with vitals and physical exam, as available 
• 
All labs 
• 
Imaging and procedure reports 
• 
Medication administration record 
 
All SAE correspondence with AbbVie will be sent to: PPDINDPharmacovigilance@abbvie.com 
 
For events that meet the IND safety reporting criteria, the investigator will also copy AbbVie on 
submission of SAE report to FDA. 
 
Adverse event severity 
Per investigator, adverse events will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA) using the following definitions: 
1. Mild: Adverse events and/or symptoms recorded in the medical record where no therapy 
was given to treat the event or where an over-the-counter medication/intervention ONLY 
was given to treat the event. 
2. Moderate: Adverse events and/or symptoms recorded in the medical record requiring 
prescription medication treatment. 
3. Severe: Adverse events and/or symptoms requiring any study drug discontinuation will be 
defined and coded as severe. ANEMIA events requiring blood transfusion will be coded as 
severe. 
 
Adverse event relatedness to study drug 
Per investigator, adverse events will be assessed for relatedness to study drug according to the 
following definitions: 
• 
Reasonable possibility (“associated”): An adverse event where there is evidence to 
suggest a causal relationship between the study drug and the adverse event 
• 
No reasonable possibility (“not associated”): An adverse event where there is no 
evidence to suggest a causal relationship between the study drug and the adverse event. 
 
Pregnancy 


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Pregnancy should be avoided starting from screening through 30 days after completion of study 
drug. If a pregnancy occurs, it should be reported to the sponsor within 24 hours of the site learning 
of the event. The administration of DAAs to that subject may be continued at site investigators 
discretion and in consultation with the study’s principal investigator after discussion with the 
subject, if the benefit of continuing DAAs is felt to outweigh the potential risk. 
 
Toxicity 
Abnormal laboratory values that occur during the study period will be evaluated by the 
investigator. Those that are deemed “clinically significant” by the investigator, or require  
intervention will be classified as adverse events and will be managed and followed until clinical 
resolution. 
• 
Management of ALT elevations while on study drug: if subject experiences a post-
baseline increase in ALT > 5x ULN and > 2x baseline value, a repeat ALT measurement 
will be performed – if confirmed, the following procedures will be done: 
o Evaluation for alternate etiology  
o Management as medically appropriate 
o Repetition of liver chemistries within one week, and until resolution 
o Discontinuation of study drug if a) ALT level > 8x ULN in absence of alternate 
etiology, or b) increasing direct bilirubin or INR or onset of hepatitis signs or 
symptoms 
 
Acute rejection or graft failure 
If at any time a patient experiences either presumed or biopsy proven rejection, this will be 
reported as an adverse event. Graft failure will also be reported as an adverse event.  
 
Product complaint 
A product complaint is defined as any written, electronic, or oral communication that alleges 
deficiencies related to the physical characteristics, identity, quality, purity, potency, durability, 
reliability, safety, effectiveness, or performance of a product after it is released for distribution. 
 
Product complaints must be reported to AbbVie within 24 hours of the time it is observed. 
Principal Investigator will report product complaints that involve to AbbVie products to: 
RD_PQC_QS@abbvie.com  
 
3.10 
References 
United States Renal Data System. 2019 USRDS annual data report: Epidemiology of kidney 
disease in the United States. National Institutes of Health, National Institute of Diabetes and 
Digestive and Kidney Diseases, Bethesda, MD, 2018.  
Hart, A., J.M. Smith, M.A. Skeans, et al., OPTN/SRTR 2017 Annual Data Report: Kidney. Am J 
Transplant, 2019. 19 Suppl 2: p. 19-123 
Reese, P.P., P.L. Abt, E.A. Blumberg, and D.S. Goldberg, Transplanting Hepatitis C-Positive 
Kidneys. N Engl J Med, 2015. 373(4): p. 303-5 
Chute, D.F. and M.E. Sise, Effect of the Opioid Crisis on the Donor Pool for Kidney 
Transplantation: An Analysis of National Kidney Deceased Donor Trends from 2010-2016. Am J 
Nephrol, 2018. 47(2): p. 84-93 
Chute, D.F., R.T. Chung, and M.E. Sise, Direct-acting antiviral therapy for hepatitis C virus 
infection in the kidney transplant recipient. Kidney international, 2018. 93(3): p. 560-567 
Durand, C.M., M.G. Bowring, D.M. Brown, et al., Direct-Acting Antiviral Prophylaxis in Kidney 
Transplantation From Hepatitis C Virus-Infected Donors to Noninfected Recipients: An Open-
Label Nonrandomized Trial. Annals of internal medicine, 2018. 168(8): p. 533-540 


AbbVie Investigator-Initiated Studies (IIS): Required Protocol Components 
 
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Version: 5.0, December 16, 2022 
Potluri, V.S., D.S. Goldberg, S. Mohan, et al., National Trends in Utilization and 1-Year Outcomes 
with Transplantation of HCV-Viremic Kidneys. Journal of the American Society of Nephrology : 
JASN, 2019. 30(10): p. 1939-1951 
Reese, P.P., P.L. Abt, E.A. Blumberg, et al., Twelve-Month Outcomes After Transplant of 
Hepatitis C-Infected Kidneys Into Uninfected Recipients: A Single-Group Trial. Annals of internal 
medicine, 2018. 169(5): p. 273-281 
Kadatz, M., S. Klarenbach, J. Gill, and J.S. Gill, Cost-effectiveness of using kidneys from hepatitis 
C nucleic acid test–positive donors for transplantation in hepatitis C–negative recipients. 2018. 
18(10): p. 2457-2464 
Kapila, N., K.V.N. Menon, K. Al-Khalloufi, et al., HCV NAT positive solid organ allografts 
transplanted into HCV negative recipients: A real-world experience. Hepatology (Baltimore, Md.), 
2019: p. 10.1002/hep.31011 
Molnar, M.Z., S. Nair, O. Cseprekal, et al., Transplantation of kidneys from hepatitis C-infected 
donors to hepatitis C-negative recipients: Single center experience. American journal of 
transplantation : official journal of the American Society of Transplantation and the American 
Society of Transplant Surgeons, 2019. 19(11): p. 3046-3057 
 
3.11 
Study 
Timelines 
Provide the estimated study timelines below: 
 
Milestone 
Est. Date (Month/Year) 
Duration* 
18 months 
First Subject First Visit (FSFV) 
 May 2021 
Last Subject Last Visit (LSLV) 
December 2024 
Final Report (e.g., manuscript/ 
publication) 
August 2025 
*Duration is defined as FSFV to LSLV in months.