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| Name | Class |
|---|---|
| Merck Sharp & Dohme LLC | INDUSTRY |
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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 Grazoprevir (GZR) 100 mg/Elbasvir (EBR) 50 mg administered on-call to the operating room for the renal transplant procedure and continued for 12 weeks post-renal transplant.
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. Hepatitis C treatment will include Grazoprevir (GZR) 100 mg/Elbasvir (EBR) 50 mg administered on-call to the operating room for the renal transplant procedure and continued for 12 weeks post-renal transplant. The donor hepatitis C genotype will be tested. If the donor has genotype 1a without resistance or genotype 1b treatment will remain GZR/EBR for 12 weeks. If the donor has genotype 1a with resistance variants, then Ribavirin will be added and treatment will be given for 16 weeks starting from the date ribavirin was added. If the donor has hepatitis C genotype 2 or 3, Sofosbuvir will be added and treatment will be for 12 weeks from the date Sofosbuvir was added.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Donor genotype 1a no resistance or 1b | Experimental | Participants who receive donors found to have hepatitis C genotype 1a without resistance Zepatier one tablet daily for 12 weeks |
|
| Donor genotype 1a with resistance | Experimental | 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 |
|
| Donor genotype 2 or 3 | Experimental | 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Zepatier | Drug | Fixed dose Grazoprevir 100 mg/Elbasvir 50 mg by mouth daily for 12 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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. | 12 weeks after transplant |
| Measure | Description | Time Frame |
|---|---|---|
| Viral Response | 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 | 12 weeks after completing treatment |
| Antibody Development |
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Inclusion Criteria:
Participants ≥ 50 years old
On the deceased donor kidney waiting list at Johns Hopkins Hospital
Awaiting a first kidney transplant
No available living kidney donors
On hemodialysis or peritoneal dialysis or stage 5 chronic kidney disease (CKD) defined as a glomerular filtration rate < 15 ml/min for ≥ past 90 days
HCV-uninfected (by both antibody and RNA PCR) and without any behavioral risk factors for contracting HCV other than being on hemodialysis.
Calculated panel reactive anti-human leukocyte antigen (HLA) antibody (cPRA) below 20 percent
Female who is:
Males who are not surgically sterile and are sexually active with female partner(s) of childbearing potential must agree to practice two effective forms of birth control (as outlined in the participant information and consent form) throughout the course of the study, starting with starting with Study Day 1 and for 30 days after stopping study drug, or for 6 months after stopping study drug if receiving ribavirin (RBV)
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Johns Hopkins Hospital | Baltimore | Maryland | 21205 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29507971 | Derived | Durand CM, Bowring MG, Brown DM, Chattergoon MA, Massaccesi G, Bair N, Wesson R, Reyad A, Naqvi FF, Ostrander D, Sugarman J, Segev DL, Sulkowski M, Desai NM. 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. doi: 10.7326/M17-2871. Epub 2018 Mar 6. |
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Peer reviewed publications
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| ID | Title | Description |
|---|---|---|
| FG000 | Donor Genotype 1a no Resistance or 1b | 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 |
| FG001 | Donor Genotype 1a With Resistance | 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 |
| FG002 | Donor Genotype 2 or 3 | 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
There were no participants who received a kidney from a donor with genotype 1a infection and resistance. Therefore this population is zero.
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| ID | Title | Description |
|---|---|---|
| BG000 | Donor Genotype 1a no Resistance or 1b | 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 |
| BG001 | Donor Genotype 1a With Resistance |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | 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. | There were no participants who received donors found to have hepatitis C genotype 1a with resistance enrolled. | Posted | Count of Participants | Participants | 12 weeks after transplant |
Adverse events were collected for 6 months from initiation of treatment
10 patients overall were at risk of adverse events, none of them from the Donor Genotype 1a With Resistance arm
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Donor Genotype 1a no Resistance or 1b | 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 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pulomonary infection | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Christine Durand, MD | Johns Hopkins University | 410-955-5684 | cdurand2@jhmi.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 11, 2017 | Aug 8, 2018 | Prot_SAP_001.pdf |
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| ID | Term |
|---|---|
| D007676 | Kidney Failure, Chronic |
| D006526 | Hepatitis C |
| ID | Term |
|---|---|
| D051436 | Renal Insufficiency, Chronic |
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
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| ID | Term |
|---|---|
| C000611265 | elbasvir-grazoprevir drug combination |
| C578009 | grazoprevir |
| C000589335 | elbasvir |
| D012254 | Ribavirin |
| D000069474 | Sofosbuvir |
| ID | Term |
|---|---|
| D012263 | Ribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D014542 | Uridine Monophosphate |
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|
| Ribavirin | Drug | Ribavirin 1200 mg/d (> 75 kg) or 1000 mg/d (< 75 kg) by mouth daily in two divided doses |
|
|
| Sofosbuvir | Drug | Sofosbuvir 400 mg daily |
|
|
Number of kidney transplant recipients who become reactive for HCV antibody |
| 12 weeks |
| Number of Participants With Nonstructural Protein 5A (NS5A) Resistance Mutations in the HCV Population From the Deceased Donors | Number of participants with NS5A resistance mutations in the HCV population from the deceased donors. Number of donors with NS5A resistance mutations | Baseline |
| IP-10 Elevations | Measurement of interferon (IFN)-gamma inducible protein 10 (IP-10) a marker of acute hepatitis C infection. | 12 weeks |
| Kidney Function at 6 Months | Serum creatinine mg/dL at 6 months following transplantation | 6 months following transplantation |
| Kidney Function at 12 Months | Serum creatinine mg/dL at 12 months following transplantation | 12 months following transplantation |
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 |
| BG002 | Donor Genotype 2 or 3 | 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 |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Median | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Hepatitis C virus (HCV) antibody negative | Count of Participants | Participants |
|
| ID |
|---|
| Title |
|---|
| Description |
|---|
| OG000 | Donor Genotype 1a no Resistance or 1b | 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 |
| OG001 | Donor Genotype 1a With Resistance | 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 |
| OG002 | Donor Genotype 2 or 3 | 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 |
|
|
| Secondary | Viral Response | 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 | There were no participants who received a kidney from a donor with genotype 1a infection and resistance. Therefore this population is zero. | Posted | Count of Participants | Participants | 12 weeks after completing treatment |
|
|
|
| Secondary | Antibody Development | Number of kidney transplant recipients who become reactive for HCV antibody | There were no participants who received a kidney from a donor with genotype 1a infection and resistance. Therefore this population is zero. | Posted | Count of Participants | Participants | 12 weeks |
|
|
|
| Secondary | Number of Participants With Nonstructural Protein 5A (NS5A) Resistance Mutations in the HCV Population From the Deceased Donors | Number of participants with NS5A resistance mutations in the HCV population from the deceased donors. Number of donors with NS5A resistance mutations | There were no participants who received a kidney from a donor with genotype 1a infection and resistance. Therefore this population is zero. | Posted | Count of Participants | Participants | Baseline |
|
|
|
| Secondary | IP-10 Elevations | Measurement of interferon (IFN)-gamma inducible protein 10 (IP-10) a marker of acute hepatitis C infection. | Data were not collected | Posted | 12 weeks |
|
|
| Secondary | Kidney Function at 6 Months | Serum creatinine mg/dL at 6 months following transplantation | There were no participants who received a kidney from a donor with genotype 1a infection and resistance. Therefore this population is zero. | Posted | Median | Full Range | mg/dL | 6 months following transplantation |
|
|
|
| Secondary | Kidney Function at 12 Months | Serum creatinine mg/dL at 12 months following transplantation | There were no participants who received a kidney from a donor with genotype 1a infection and resistance. Therefore this population is zero. | Posted | Median | Full Range | mg/dL | 12 months following transplantation |
|
|
|
| 0 |
| 7 |
| 3 |
| 7 |
| 0 |
| 7 |
| EG001 | Donor Genotype 1a With Resistance | 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 | 0 | 0 | 0 | 0 | 0 | 0 |
| EG002 | Donor Genotype 2 or 3 | 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 | 0 | 3 | 1 | 3 | 0 | 3 |
| Urinary tract infection | Renal and urinary disorders | Systematic Assessment |
|
| blood stream infection | Blood and lymphatic system disorders | Systematic Assessment |
|
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| D052776 |
| Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D006525 | Hepatitis, Viral, Human |
| D014777 | Virus Diseases |
| D018178 | Flaviviridae Infections |
| D012327 | RNA Virus Infections |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D014500 | Uracil Nucleotides |
| D011742 | Pyrimidine Nucleotides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009711 | Nucleotides |
| D012265 | Ribonucleotides |