MYTHIC: Multi-center Study to Transplant Hepatitis-C Infected Kidneys

• Sponsor: Raymond Chung (Other)
• Overall Status: Completed
• CT.gov ID: NCT03781726
• Collaborator: AbbVie (Industry), University of Pennsylvania (Other), Johns Hopkins University (Other), University of Cincinnati (Other), Weill Medical College of Cornell University (Other), University of Michigan (Other), Northwestern University (Other)
• Enrollment: 30
• Locations: 7
• Arm: 1
• Actual Duration (Months): 32.7
• Patients Per Site: 4.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Open label multi center study for the donation of HCV positive kidneys to HCV negative recipients with interventional treatment to prevent HCV transmission upon transplantation.

Condition or Disease	Intervention/Treatment	Phase
Renal Failure Chronic; Hepatitis C	Drug: glecaprevir/pibrentasvir treatment	Phase 4

Detailed Description

The study objective is to determine if the administration of the direct acting antiviral glecaprevir/pibrentasvir for 8 weeks after kidney transplantation is both safe and effective at preventing the spread of HCV infection from donor kidney with known HCV infection (all genotypes) to an HCV negative recipient as evidenced by a negative HCV viral RNA at 12 weeks post treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Multi-Center, Open-Label Study of Glecaprevir/Pibrentasvir to Treat Recipients of Transplanted Kidneys From Deceased Donors With Hepatitis C Virus
• Actual Study Start Date: Apr 10, 2019
• Actual Primary Completion Date: Mar 20, 2020
• Actual Study Completion Date: Dec 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment with glecaprevir/pibrentasvir Fixed Dose Combination 8 weeks of HCV treatment with combination tablet of glecaprevir and pibrentasvir	Drug: glecaprevir/pibrentasvir treatment; combination treatment with glecaprevir and pibrentasvir fixed dose tablet.; Other Names: Mavyret treatment

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Undetectable HCV [12 weeks post treatment]

   HCV RNA < LLOQ 12 weeks after the last actual dose of G/P

Secondary Outcome Measures

1. Percentage of Subjects With On-treatment Virologic Failure [During 8 week treatment course]

   HCV RNA > LLOQ during G/P treatment

2. Percentage of Subjects With Post-treatment Virologic Relapse [During 12 week post treatment follow-up]

   HCV RNA > LLOQ after completion of G/P treatment and prior HCV RNA < LLOQ while on treatment

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Recipient Inclusion Criteria:

• Estimated glomerular filtration rate(eGFR) < 15 ml/min/1.73 m2

• Listed for an isolated kidney transplantation

• Able to understand and adhere to the study visit schedule and all other protocol requirements, and must voluntarily sign and date an informed consent

• No available medically acceptable, compatible living kidney donor

• Subject must agree to use an effective method of birth control per protocol specifications

Recipient Exclusion Criteria:

• History of severe, life-threatening or other significant sensitivity to immunosuppressants utilized in kidney transplant

• Female who is pregnant, breastfeeding, or is planning to become pregnant during the course of the study

• History of HIV

• HCV RNA positive

• HBV surface Ag-positive or detectable HBV DNA

• Primary focal segmental glomerulosclerosis (FSGS) or disease process with increased risk of causing early graft failure as assessed by the transplant nephrologist and/or investigator team

• Presence of clinically significant liver disease

• Transplant candidate requiring antibody desensitization protocol for transplantation

• Most recent calculated panel reactive antibody (cPRA) >80%.

• Prior recipient of a non-renal solid organ transplant

Donor Organ Inclusion Criteria

• Deceased donor organ with kidney donor profile index (KDPI) ≤0.85

• HCV RNA-positive

Donor Organ Exclusion Criteria

• Known prior HCV treatment with direct acting antiviral medication

• HIV RNA-positive

• HBV Surface antigen-positive or HBV DNA-positive

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northwestern Medicine	Chicago	Illinois	United States	60611
2	John Hopkins	Baltimore	Maryland	United States	21287
3	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
4	University of Michigan	Ann Arbor	Michigan	United States	48109
5	Weill Cornell Medical Center	New York	New York	United States	10065
6	University of Cincinnati Medical Center	Cincinnati	Ohio	United States	45219
7	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• Raymond Chung
• AbbVie
• University of Pennsylvania
• Johns Hopkins University
• University of Cincinnati
• Weill Medical College of Cornell University
• University of Michigan
• Northwestern University

Investigators

• Principal Investigator: Raymond T Chung, MD, Massachusetts General Hospital

Study Documents (Full-Text)

• Study Protocol - Feb 13, 2019
• Statistical Analysis Plan - Apr 26, 2020

More Information

Publications

None provided.

• Responsible Party: Raymond Chung, Director of Hepatology, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT03781726
• Other Study ID Numbers: 2018P003140
• First Posted: Dec 20, 2018
• Last Update Posted: Jan 26, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Raymond Chung, Director of Hepatology, Massachusetts General Hospital: hemodialysis; renal failure; kidney transplant
• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis; Renal Insufficiency; Kidney Failure, Chronic

Study Results

Participant Flow

Arm/Group Title	NAT+ Kidney Transplant Treatment With Glecaprevir/Pibrentasvir Fixed Dose Combination (Arm 1)
Arm/Group Description	8 weeks of HCV treatment with combination tablet of glecaprevir and pibrentasvir glecaprevir/pibrentasvir treatment: combination treatment with glecaprevir and pibrentasvir fixed dose tablet.
Period Title: Overall Study
STARTED	30
COMPLETED	28
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	NAT+ Kidney Transplant Treatment With Glecaprevir/Pibrentasvir Fixed Dose Combination (Arm 1)
Arm/Group Description	8 weeks of HCV treatment with combination tablet of glecaprevir and pibrentasvir glecaprevir/pibrentasvir treatment: combination treatment with glecaprevir and pibrentasvir fixed dose tablet.
Overall Participants	30
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	57
Sex: Female, Male (Count of Participants)
Female	9 30%
Male	21 70%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 3.3%
Not Hispanic or Latino	29 96.7%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	9 30%
White	20 66.7%
More than one race	0 0%
Unknown or Not Reported	1 3.3%
Kidney disease etiology (Count of Participants)
Diabetic nephropathy	11 36.7%
Hypertension	9 30%
Polycystic kidney disease	3 10%
Congenital/genetic	2 6.7%
IgA nephropathy	3 10%
Other	2 6.7%
On dialysis at baseline (Count of Participants)
Yes	27 90%
No	3 10%
Time from consent to transplant (Weeks) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [Weeks]	6.29
Time spent on waitlist at time of consent (Weeks) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [Weeks]	137
BMI (kg/m^2) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [kg/m^2]	29.5

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Undetectable HCV
Description	HCV RNA < LLOQ 12 weeks after the last actual dose of G/P
Time Frame	12 weeks post treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NAT+ Kidney Transplant Treatment With Glecaprevir/Pibrentasvir Fixed Dose Combination (Arm 1)
Arm/Group Description	8 weeks of HCV treatment with combination tablet of glecaprevir and pibrentasvir glecaprevir/pibrentasvir treatment: combination treatment with glecaprevir and pibrentasvir fixed dose tablet.
Measure Participants	30
Count of Participants [Participants]	30 100%

2. Secondary Outcome

Title	Percentage of Subjects With On-treatment Virologic Failure
Description	HCV RNA > LLOQ during G/P treatment
Time Frame	During 8 week treatment course

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NAT+ Kidney Transplant Treatment With Glecaprevir/Pibrentasvir Fixed Dose Combination (Arm 1)
Arm/Group Description	8 weeks of HCV treatment with combination tablet of glecaprevir and pibrentasvir glecaprevir/pibrentasvir treatment: combination treatment with glecaprevir and pibrentasvir fixed dose tablet.
Measure Participants	30
Count of Participants [Participants]	12 40%

3. Secondary Outcome

Title	Percentage of Subjects With Post-treatment Virologic Relapse
Description	HCV RNA > LLOQ after completion of G/P treatment and prior HCV RNA < LLOQ while on treatment
Time Frame	During 12 week post treatment follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NAT+ Kidney Transplant Treatment With Glecaprevir/Pibrentasvir Fixed Dose Combination (Arm 1)
Arm/Group Description	8 weeks of HCV treatment with combination tablet of glecaprevir and pibrentasvir glecaprevir/pibrentasvir treatment: combination treatment with glecaprevir and pibrentasvir fixed dose tablet.
Measure Participants	30
Count of Participants [Participants]	0 0%

Adverse Events

Time Frame	Baseline (day of transplant) to one year post transplant (1 year total)
Arm/Group Title	NAT+ Kidney Transplant Treatment With Glecaprevir/Pibrentasvir Fixed Dose Combination (Arm 1)
Arm/Group Description	8 weeks of HCV treatment with combination tablet of glecaprevir and pibrentasvir glecaprevir/pibrentasvir treatment: combination treatment with glecaprevir and pibrentasvir fixed dose tablet.
All Cause Mortality
	NAT+ Kidney Transplant Treatment With Glecaprevir/Pibrentasvir Fixed Dose Combination (Arm 1)
	Affected / at Risk (%)	# Events
Total	2/30 (6.7%)
Serious Adverse Events
	NAT+ Kidney Transplant Treatment With Glecaprevir/Pibrentasvir Fixed Dose Combination (Arm 1)
	Affected / at Risk (%)	# Events
Total	20/30 (66.7%)
Blood and lymphatic system disorders
neutrophil count decreased	2/30 (6.7%)	2
febrile neutropenia	1/30 (3.3%)	1
hemorrhoidal hemorrhage	1/30 (3.3%)	1
Cardiac disorders
heart failure	1/30 (3.3%)	1
chest pain	1/30 (3.3%)	1
Gastrointestinal disorders
vomiting	1/30 (3.3%)	1
gastritis	2/30 (6.7%)	3
small intestinal obstruction	1/30 (3.3%)	1
ileus	1/30 (3.3%)	2
abdominal infection	1/30 (3.3%)	3
constipation	1/30 (3.3%)	1
Immune system disorders
acute cellular rejection	2/30 (6.7%)	2
Infections and infestations
coronavirus infection	1/30 (3.3%)	1
fever	1/30 (3.3%)	1
cytomegalovirus infection reactivation	1/30 (3.3%)	1
sepsis	1/30 (3.3%)	1
Injury, poisoning and procedural complications
postoperative hemorrhage	1/30 (3.3%)	1
drug toxicity due to accidental overdosage	1/30 (3.3%)	1
Nervous system disorders
stroke	1/30 (3.3%)	1
Renal and urinary disorders
acute kidney injury	1/30 (3.3%)	4
renal calculi	1/30 (3.3%)	1
post procedural urine leak	1/30 (3.3%)	1
renal graft function delayed	1/30 (3.3%)	1
dysuria	1/30 (3.3%)	1
urinary tract obstruction	1/30 (3.3%)	1
Respiratory, thoracic and mediastinal disorders
hypotension	2/30 (6.7%)	2
syncope	1/30 (3.3%)	1
Other (Not Including Serious) Adverse Events
	NAT+ Kidney Transplant Treatment With Glecaprevir/Pibrentasvir Fixed Dose Combination (Arm 1)
	Affected / at Risk (%)	# Events
Total	27/30 (90%)
Blood and lymphatic system disorders
anemia	2/30 (6.7%)	2
neutrophil count decreased	2/30 (6.7%)	2
platelet count decreased	2/30 (6.7%)	2
white blood cell count decreased	4/30 (13.3%)	5
Endocrine disorders
hyperglycemia	6/30 (20%)	6
Gastrointestinal disorders
abdominal pain	6/30 (20%)	6
constipation	2/30 (6.7%)	2
gastritis	3/30 (10%)	3
gastroesophageal reflux disease	2/30 (6.7%)	2
vomiting	3/30 (10%)	3
General disorders
chills	2/30 (6.7%)	2
fatigue	3/30 (10%)	3
nausea	3/30 (10%)	3
Immune system disorders
acute cellular rejection	2/30 (6.7%)	2
Infections and infestations
cytomegalovirus infection reactivation	2/30 (6.7%)	2
Musculoskeletal and connective tissue disorders
pain in extremity	2/30 (6.7%)	2
Nervous system disorders
dizziness	7/30 (23.3%)	8
headache	3/30 (10%)	3
tremor	5/30 (16.7%)	5
Psychiatric disorders
anxiety	2/30 (6.7%)	2
Renal and urinary disorders
acute kidney injury	2/30 (6.7%)	5
bladder spasm	2/30 (6.7%)	2
creatinine increased	3/30 (10%)	3
hyperkalemia	4/30 (13.3%)	5
renal graft function delayed	2/30 (6.7%)	2
urinary retention	3/30 (10%)	3
urinary tract infection	3/30 (10%)	7
Respiratory, thoracic and mediastinal disorders
dyspnea	3/30 (10%)	4
nasal congestion	2/30 (6.7%)	2
Vascular disorders
edema limbs	3/30 (10%)	3
hypertension	5/30 (16.7%)	5
hypotension	5/30 (16.7%)	6

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.