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Trial record 55 of 82 for:    GRAZOPREVIR ANHYDROUS AND ELBASVIR

Exploring Renal Transplants Using Hepatitis C Infected Donors for HCV-negative Recipients (EXPANDER-1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02781649
Recruitment Status : Completed
First Posted : May 24, 2016
Results First Posted : April 5, 2018
Last Update Posted : September 6, 2018
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Johns Hopkins University

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions End-Stage Renal Disease
Hepatitis C
Interventions Drug: Zepatier
Drug: Ribavirin
Drug: Sofosbuvir
Enrollment 10
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Donor Genotype 1a no Resistance or 1b Donor Genotype 1a With Resistance Donor Genotype 2 or 3
Hide Arm/Group Description

Participants who receive donors found to have hepatitis C genotype 1a without resistance Zepatier one tablet daily for 12 weeks

Zepatier: Fixed dose Grazoprevir 100 mg/Elbasvir 50 mg by mouth daily for 12 weeks

Participants who receive donors found to have hepatitis C genotype 1a with nonstructural protein 5A associated resistance mutations Zepatier one tablet daily for 16 weeks Ribavirin weight based dosing for 16 weeks

Zepatier: Fixed dose Grazoprevir 100 mg/Elbasvir 50 mg by mouth daily for 12 weeks

Ribavirin: Ribavirin 1200 mg/d (> 75 kg) or 1000 mg/d (< 75 kg) by mouth daily in two divided doses

Participants who receive donors found to have hepatitis C genotype 2 or 3 Zepatier one tablet daily for 12 weeks Sofosbuvir 400 mg daily for 12 weeks

Zepatier: Fixed dose Grazoprevir 100 mg/Elbasvir 50 mg by mouth daily for 12 weeks

Sofosbuvir: Sofosbuvir 400 mg daily

Period Title: Overall Study
Started 7 [1] 0 3
Completed 7 0 3
Not Completed 0 0 0
[1]
4 in this group had insufficient viral RNA for genotyping. They were treated as 1a
Arm/Group Title Donor Genotype 1a no Resistance or 1b Donor Genotype 1a With Resistance Donor Genotype 2 or 3 Total
Hide Arm/Group Description

Participants who receive donors found to have hepatitis C genotype 1a without resistance Zepatier one tablet daily for 12 weeks

Zepatier: Fixed dose Grazoprevir 100 mg/Elbasvir 50 mg by mouth daily for 12 weeks

Participants who receive donors found to have hepatitis C genotype 1a with nonstructural protein 5A associated resistance mutations Zepatier one tablet daily for 16 weeks Ribavirin weight based dosing for 16 weeks

Zepatier: Fixed dose Grazoprevir 100 mg/Elbasvir 50 mg by mouth daily for 12 weeks

Ribavirin: Ribavirin 1200 mg/d (> 75 kg) or 1000 mg/d (< 75 kg) by mouth daily in two divided doses

Participants who receive donors found to have hepatitis C genotype 2 or 3 Zepatier one tablet daily for 12 weeks Sofosbuvir 400 mg daily for 12 weeks

Zepatier: Fixed dose Grazoprevir 100 mg/Elbasvir 50 mg by mouth daily for 12 weeks

Sofosbuvir: Sofosbuvir 400 mg daily

Total of all reporting groups
Overall Number of Baseline Participants 7 0 3 10
Hide Baseline Analysis Population Description
There were no participants who received a kidney from a donor with genotype 1a infection and resistance. Therefore this population is zero.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 0 participants 3 participants 10 participants
<=18 years
0
   0.0%
0
0
   0.0%
0
   0.0%
Between 18 and 65 years
0
   0.0%
0
2
  66.7%
2
  20.0%
>=65 years
7
 100.0%
0
1
  33.3%
8
  80.0%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 7 participants 0 participants 3 participants 10 participants
71
(65 to 76)
61
(57 to 74)
71
(57 to 76)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 0 participants 3 participants 10 participants
Female
1
  14.3%
0
1
  33.3%
2
  20.0%
Male
6
  85.7%
0
2
  66.7%
8
  80.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 0 participants 3 participants 10 participants
American Indian or Alaska Native
0
   0.0%
0
0
   0.0%
0
   0.0%
Asian
1
  14.3%
0
0
   0.0%
1
  10.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
1
  33.3%
1
  10.0%
White
6
  85.7%
0
2
  66.7%
8
  80.0%
More than one race
0
   0.0%
0
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 7 participants 0 participants 3 participants 10 participants
7 3 10
Hepatitis C virus (HCV) antibody negative  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 0 participants 3 participants 10 participants
7
 100.0%
0
3
 100.0%
10
 100.0%
1.Primary Outcome
Title Number of Participants With Grade 3 or Higher Treatment-related Adverse Events as US Department of Health and Human Services Common Terminology of Adverse Events (CTCAE) Version 4
Hide Description Proportion of participants with grade 3 or higher treatment-related adverse events (AE) as assessed by US Department of Health and Human Services Common Terminology of AEs version 4. An AE is an unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5. Grade 3 Severe or medically significant but not life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE. The investigator will determine if the AE is related to the treatment.
Time Frame 12 weeks after transplant
Hide Outcome Measure Data
Hide Analysis Population Description
There were no participants who received donors found to have hepatitis C genotype 1a with resistance enrolled.
Arm/Group Title Donor Genotype 1a no Resistance or 1b Donor Genotype 1a With Resistance Donor Genotype 2 or 3
Hide Arm/Group Description:

Participants who receive donors found to have hepatitis C genotype 1a without resistance Zepatier one tablet daily for 12 weeks

Zepatier: Fixed dose Grazoprevir 100 mg/Elbasvir 50 mg by mouth daily for 12 weeks

Participants who receive donors found to have hepatitis C genotype 1a with nonstructural protein 5A associated resistance mutations Zepatier one tablet daily for 16 weeks Ribavirin weight based dosing for 16 weeks

Zepatier: Fixed dose Grazoprevir 100 mg/Elbasvir 50 mg by mouth daily for 12 weeks

Ribavirin: Ribavirin 1200 mg/d (> 75 kg) or 1000 mg/d (< 75 kg) by mouth daily in two divided doses

Participants who receive donors found to have hepatitis C genotype 2 or 3 Zepatier one tablet daily for 12 weeks Sofosbuvir 400 mg daily for 12 weeks

Zepatier: Fixed dose Grazoprevir 100 mg/Elbasvir 50 mg by mouth daily for 12 weeks

Sofosbuvir: Sofosbuvir 400 mg daily

Overall Number of Participants Analyzed 7 0 3
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
0
   0.0%
2.Secondary Outcome
Title Viral Response
Hide Description This is the number of participants with undetectable hepatitis C RNA in the blood at 12 weeks after stopping treatment. Proportion of kidney transplant recipients with HCV RNA < Lower Limit Of Quantification (LLOQ) at week 12
Time Frame 12 weeks after completing treatment
Hide Outcome Measure Data
Hide Analysis Population Description
There were no participants who received a kidney from a donor with genotype 1a infection and resistance. Therefore this population is zero.
Arm/Group Title Donor Genotype 1a no Resistance or 1b Donor Genotype 1a With Resistance Donor Genotype 2 or 3
Hide Arm/Group Description:

Participants who receive donors found to have hepatitis C genotype 1a without resistance Zepatier one tablet daily for 12 weeks

Zepatier: Fixed dose Grazoprevir 100 mg/Elbasvir 50 mg by mouth daily for 12 weeks

Participants who receive donors found to have hepatitis C genotype 1a with nonstructural protein 5A associated resistance mutations Zepatier one tablet daily for 16 weeks Ribavirin weight based dosing for 16 weeks

Zepatier: Fixed dose Grazoprevir 100 mg/Elbasvir 50 mg by mouth daily for 12 weeks

Ribavirin: Ribavirin 1200 mg/d (> 75 kg) or 1000 mg/d (< 75 kg) by mouth daily in two divided doses

Participants who receive donors found to have hepatitis C genotype 2 or 3 Zepatier one tablet daily for 12 weeks Sofosbuvir 400 mg daily for 12 weeks

Zepatier: Fixed dose Grazoprevir 100 mg/Elbasvir 50 mg by mouth daily for 12 weeks

Sofosbuvir: Sofosbuvir 400 mg daily

Overall Number of Participants Analyzed 7 0 3
Measure Type: Count of Participants
Unit of Measure: Participants
7
 100.0%
0
3
 100.0%
3.Secondary Outcome
Title Antibody Development
Hide Description Number of kidney transplant recipients who become reactive for HCV antibody
Time Frame 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
There were no participants who received a kidney from a donor with genotype 1a infection and resistance. Therefore this population is zero.
Arm/Group Title Donor Genotype 1a no Resistance or 1b Donor Genotype 1a With Resistance Donor Genotype 2 or 3
Hide Arm/Group Description:

Participants who receive donors found to have hepatitis C genotype 1a without resistance Zepatier one tablet daily for 12 weeks

Zepatier: Fixed dose Grazoprevir 100 mg/Elbasvir 50 mg by mouth daily for 12 weeks

Participants who receive donors found to have hepatitis C genotype 1a with nonstructural protein 5A associated resistance mutations Zepatier one tablet daily for 16 weeks Ribavirin weight based dosing for 16 weeks

Zepatier: Fixed dose Grazoprevir 100 mg/Elbasvir 50 mg by mouth daily for 12 weeks

Ribavirin: Ribavirin 1200 mg/d (> 75 kg) or 1000 mg/d (< 75 kg) by mouth daily in two divided doses

Participants who receive donors found to have hepatitis C genotype 2 or 3 Zepatier one tablet daily for 12 weeks Sofosbuvir 400 mg daily for 12 weeks

Zepatier: Fixed dose Grazoprevir 100 mg/Elbasvir 50 mg by mouth daily for 12 weeks

Sofosbuvir: Sofosbuvir 400 mg daily

Overall Number of Participants Analyzed 7 0 3
Measure Type: Count of Participants
Unit of Measure: Participants
3
  42.9%
0
2
  66.7%
4.Secondary Outcome
Title Number of Participants With Nonstructural Protein 5A (NS5A) Resistance Mutations in the HCV Population From the Deceased Donors
Hide Description

Number of participants with NS5A resistance mutations in the HCV population from the deceased donors.

Number of donors with NS5A resistance mutations

Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
There were no participants who received a kidney from a donor with genotype 1a infection and resistance. Therefore this population is zero.
Arm/Group Title Donor Genotype 1a no Resistance or 1b Donor Genotype 1a With Resistance Donor Genotype 2 or 3
Hide Arm/Group Description:

Participants who receive donors found to have hepatitis C genotype 1a without resistance Zepatier one tablet daily for 12 weeks

Zepatier: Fixed dose Grazoprevir 100 mg/Elbasvir 50 mg by mouth daily for 12 weeks

Participants who receive donors found to have hepatitis C genotype 1a with nonstructural protein 5A associated resistance mutations Zepatier one tablet daily for 16 weeks Ribavirin weight based dosing for 16 weeks

Zepatier: Fixed dose Grazoprevir 100 mg/Elbasvir 50 mg by mouth daily for 12 weeks

Ribavirin: Ribavirin 1200 mg/d (> 75 kg) or 1000 mg/d (< 75 kg) by mouth daily in two divided doses

Participants who receive donors found to have hepatitis C genotype 2 or 3 Zepatier one tablet daily for 12 weeks Sofosbuvir 400 mg daily for 12 weeks

Zepatier: Fixed dose Grazoprevir 100 mg/Elbasvir 50 mg by mouth daily for 12 weeks

Sofosbuvir: Sofosbuvir 400 mg daily

Overall Number of Participants Analyzed 7 0 3
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
0
   0.0%
5.Secondary Outcome
Title IP-10 Elevations
Hide Description Measurement of interferon (IFN)-gamma inducible protein 10 (IP-10) a marker of acute hepatitis C infection.
Time Frame 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Data were not collected
Arm/Group Title Donor Genotype 1a no Resistance or 1b Donor Genotype 1a With Resistance Donor Genotype 2 or 3
Hide Arm/Group Description:

Participants who receive donors found to have hepatitis C genotype 1a without resistance Zepatier one tablet daily for 12 weeks

Zepatier: Fixed dose Grazoprevir 100 mg/Elbasvir 50 mg by mouth daily for 12 weeks

Participants who receive donors found to have hepatitis C genotype 1a with nonstructural protein 5A associated resistance mutations Zepatier one tablet daily for 16 weeks Ribavirin weight based dosing for 16 weeks

Zepatier: Fixed dose Grazoprevir 100 mg/Elbasvir 50 mg by mouth daily for 12 weeks

Ribavirin: Ribavirin 1200 mg/d (> 75 kg) or 1000 mg/d (< 75 kg) by mouth daily in two divided doses

Participants who receive donors found to have hepatitis C genotype 2 or 3 Zepatier one tablet daily for 12 weeks Sofosbuvir 400 mg daily for 12 weeks

Zepatier: Fixed dose Grazoprevir 100 mg/Elbasvir 50 mg by mouth daily for 12 weeks

Sofosbuvir: Sofosbuvir 400 mg daily

Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
6.Secondary Outcome
Title Kidney Function at 6 Months
Hide Description Serum creatinine mg/dL at 6 months following transplantation
Time Frame 6 months following transplantation
Hide Outcome Measure Data
Hide Analysis Population Description
There were no participants who received a kidney from a donor with genotype 1a infection and resistance. Therefore this population is zero.
Arm/Group Title Donor Genotype 1a no Resistance or 1b Donor Genotype 1a With Resistance Donor Genotype 2 or 3
Hide Arm/Group Description:

Participants who receive donors found to have hepatitis C genotype 1a without resistance Zepatier one tablet daily for 12 weeks

Zepatier: Fixed dose Grazoprevir 100 mg/Elbasvir 50 mg by mouth daily for 12 weeks

Participants who receive donors found to have hepatitis C genotype 1a with nonstructural protein 5A associated resistance mutations Zepatier one tablet daily for 16 weeks Ribavirin weight based dosing for 16 weeks

Zepatier: Fixed dose Grazoprevir 100 mg/Elbasvir 50 mg by mouth daily for 12 weeks

Ribavirin: Ribavirin 1200 mg/d (> 75 kg) or 1000 mg/d (< 75 kg) by mouth daily in two divided doses

Participants who receive donors found to have hepatitis C genotype 2 or 3 Zepatier one tablet daily for 12 weeks Sofosbuvir 400 mg daily for 12 weeks

Zepatier: Fixed dose Grazoprevir 100 mg/Elbasvir 50 mg by mouth daily for 12 weeks

Sofosbuvir: Sofosbuvir 400 mg daily

Overall Number of Participants Analyzed 7 0 3
Median (Full Range)
Unit of Measure: mg/dL
1.12
(1.06 to 1.7)
0.9
(0.9 to 1.0)
7.Secondary Outcome
Title Kidney Function at 12 Months
Hide Description Serum creatinine mg/dL at 12 months following transplantation
Time Frame 12 months following transplantation
Hide Outcome Measure Data
Hide Analysis Population Description
There were no participants who received a kidney from a donor with genotype 1a infection and resistance. Therefore this population is zero.
Arm/Group Title Donor Genotype 1a no Resistance or 1b Donor Genotype 1a With Resistance Donor Genotype 2 or 3
Hide Arm/Group Description:

Participants who receive donors found to have hepatitis C genotype 1a without resistance Zepatier one tablet daily for 12 weeks

Zepatier: Fixed dose Grazoprevir 100 mg/Elbasvir 50 mg by mouth daily for 12 weeks

Participants who receive donors found to have hepatitis C genotype 1a with nonstructural protein 5A associated resistance mutations Zepatier one tablet daily for 16 weeks Ribavirin weight based dosing for 16 weeks

Zepatier: Fixed dose Grazoprevir 100 mg/Elbasvir 50 mg by mouth daily for 12 weeks

Ribavirin: Ribavirin 1200 mg/d (> 75 kg) or 1000 mg/d (< 75 kg) by mouth daily in two divided doses

Participants who receive donors found to have hepatitis C genotype 2 or 3 Zepatier one tablet daily for 12 weeks Sofosbuvir 400 mg daily for 12 weeks

Zepatier: Fixed dose Grazoprevir 100 mg/Elbasvir 50 mg by mouth daily for 12 weeks

Sofosbuvir: Sofosbuvir 400 mg daily

Overall Number of Participants Analyzed 7 0 3
Median (Full Range)
Unit of Measure: mg/dL
1.0
(0.9 to 1.0)
1.3
(1.0 to 2.0)
Time Frame Adverse events were collected for 6 months from initiation of treatment
Adverse Event Reporting Description 10 patients overall were at risk of adverse events, none of them from the Donor Genotype 1a With Resistance arm
 
Arm/Group Title Donor Genotype 1a no Resistance or 1b Donor Genotype 1a With Resistance Donor Genotype 2 or 3
Hide Arm/Group Description

Participants who receive donors found to have hepatitis C genotype 1a without resistance Zepatier one tablet daily for 12 weeks

Zepatier: Fixed dose Grazoprevir 100 mg/Elbasvir 50 mg by mouth daily for 12 weeks

Participants who receive donors found to have hepatitis C genotype 1a with nonstructural protein 5A associated resistance mutations Zepatier one tablet daily for 16 weeks Ribavirin weight based dosing for 16 weeks

Zepatier: Fixed dose Grazoprevir 100 mg/Elbasvir 50 mg by mouth daily for 12 weeks

Ribavirin: Ribavirin 1200 mg/d (> 75 kg) or 1000 mg/d (< 75 kg) by mouth daily in two divided doses

Participants who receive donors found to have hepatitis C genotype 2 or 3 Zepatier one tablet daily for 12 weeks Sofosbuvir 400 mg daily for 12 weeks

Zepatier: Fixed dose Grazoprevir 100 mg/Elbasvir 50 mg by mouth daily for 12 weeks

Sofosbuvir: Sofosbuvir 400 mg daily

All-Cause Mortality
Donor Genotype 1a no Resistance or 1b Donor Genotype 1a With Resistance Donor Genotype 2 or 3
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/7 (0.00%)      0/0      0/3 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Donor Genotype 1a no Resistance or 1b Donor Genotype 1a With Resistance Donor Genotype 2 or 3
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/7 (42.86%)      0/0      1/3 (33.33%)    
Blood and lymphatic system disorders       
blood stream infection   1/7 (14.29%)  1 0/0  0/3 (0.00%)  0
Renal and urinary disorders       
Urinary tract infection   2/7 (28.57%)  2 0/0  0 0/3 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Pulomonary infection   0/7 (0.00%)  0 0/0  1/3 (33.33%)  1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Donor Genotype 1a no Resistance or 1b Donor Genotype 1a With Resistance Donor Genotype 2 or 3
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/7 (0.00%)      0/0      0/3 (0.00%)    
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Christine Durand, MD
Organization: Johns Hopkins University
Phone: 410-955-5684
EMail: cdurand2@jhmi.edu
Layout table for additonal information
Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT02781649     History of Changes
Other Study ID Numbers: IRB00089751
First Submitted: May 10, 2016
First Posted: May 24, 2016
Results First Submitted: January 17, 2018
Results First Posted: April 5, 2018
Last Update Posted: September 6, 2018