End-Stage Renal DiseasePhase 4EXPANDER-1NCT02781649
Exploring Renal Transplants Using Hepatitis C Infected Donors for HCV-negative Recipients
A Phase 4 study testing Zepatier, Ribavirin and Sofosbuvir in people with End-Stage Renal Disease and Hepatitis C, run by Johns Hopkins University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- End-Stage Renal Disease, Hepatitis C
- What is being tested?
- Zepatier, Ribavirin and Sofosbuvir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Jul 2016to 1 Jan 2018
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- Calculated panel reactive anti-human leukocyte antigen (HLA) antibody (cPRA) below 20 percent
- Female who is:
- practicing total abstinence from sexual intercourse (minimum 1 complete menstrual cycle)
- sexually active with female partners only
- not of childbearing potential: defined as postmenopausal for at least 2 years prior to screening defined as amenorrheic for longer than 2 years, age appropriate, and confirmed by a follicle-stimulating hormone level indicating a postmenopausal state, or surgically sterile: defined as bilateral tubal ligation, bilateral oophorectomy or hysterectomy or has a vasectomized partner(s);
- of childbearing potential and sexually active with male partner(s): currently using at least one effective method of birth control at the time of screening and agree to practice two effective methods of birth control while receiving study drug (as outlined in the participant information and consent form starting with Study Day 1 and for 30 days after stopping study drug, or for 6 months after stopping study drug if receiving RBV (Note: Estrogen-containing hormonal contraceptives, including oral, injectable, implantable, patch and ring varieties, may not be used during study drug treatment).
- 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)
Who cannot join
- Plan to receive a multi-organ transplant
- Plan to receive a dual kidney transplant (including en bloc)
- Prior solid organ transplant
- Participating in another study that involves an intervention or investigational product
- Plan to receive a blood type incompatible kidney
- 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
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- Active or unresolved bacterial, viral, or fungal infection that is clinically significant
- History of cirrhosis or pre-existing liver disease such as non-alcoholic steatohepatitis
- History of illicit drug use or alcohol abuse within 12 months prior to screening
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-label Pilot Study to Determine the Tolerability and Efficacy of Fixed-dose Grazoprevir/Elbasvir Treatment in Hepatitis C Uninfected Recipients of Renal Transplants From Hepatitis C Infected Deceased Donors
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.
Read the 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. 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.
- Conditions
- End-Stage Renal Disease, Hepatitis C
- Being tested
- Zepatier, Ribavirin, Sofosbuvir
- Keywords
- Renal, Transplants, Hepatitis C, HCV-negative, Infected, Donors
- Medical subject headings
- Kidney Failure, Chronic, Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZepatierDrug
Also called Fixed dose Grazoprevir /Elbasvir
Fixed dose Grazoprevir 100 mg/Elbasvir 50 mg by mouth daily for 12 weeks
RibavirinDrug
Also called Rebetol, Copegus, Virazole, and Ribasphere
Ribavirin 1200 mg/d (> 75 kg) or 1000 mg/d (< 75 kg) by mouth daily in two divided doses
SofosbuvirDrug
Also called Sovaldi
Sofosbuvir 400 mg daily
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Zepatier |
| 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 Receives: Drug: Zepatier; Drug: Ribavirin |
| 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 Receives: Drug: Zepatier; Drug: Sofosbuvir |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 weeks after transplant
Secondary outcomes (6)
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
Measured: 12 weeks after completing treatment
Antibody Development
Number of kidney transplant recipients who become reactive for HCV antibody
Measured: 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
Measured: Baseline
IP-10 Elevations
Measurement of interferon (IFN)-gamma inducible protein 10 (IP-10) a marker of acute hepatitis C infection.
Measured: 12 weeks
Kidney Function at 6 Months
Serum creatinine mg/dL at 6 months following transplantation
Measured: 6 months following transplantation
Kidney Function at 12 Months
Serum creatinine mg/dL at 12 months following transplantation
Measured: 12 months following transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2016 (estimated)
- Study start20 Jul 2016
- Primary completion3 May 2017
- Study completion1 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for End-Stage Renal DiseaseStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02781649
- Sponsor's protocol ID
- IRB00089751
- Acronym
- EXPANDER-1
- Status last verified
- Aug 2018
- First submitted
- 10 May 2016
- Last updated
- 6 Sep 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: Peer reviewed publications
Publications
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.
PubMed 29507971
Study at a glance
From the registry record, last updated by the sponsor on 6 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label Pilot Study to Determine the Tolerability and Efficacy of Fixed-dose Grazoprevir/Elbasvir Treatment in Hepatitis C Uninfected Recipients of Renal Transplants From Hepatitis C Infected Deceased Donors
- ClinicalTrials.gov ID
- NCT02781649
- Acronym / sponsor ID
- EXPANDER-1 / IRB00089751
- Conditions
- End-Stage Renal Disease, Hepatitis C
- Keywords
- Renal, Transplants, Hepatitis C, HCV-negative, Infected, Donors
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 20 Jul 2016 (actual)
- Primary completion
- 3 May 2017 (actual)
- Study completion
- 1 Jan 2018 (actual)
- First posted
- 24 May 2016 (estimated)
- Results
- Posted 5 Apr 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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. 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Donor genotype 1a no resistance or 1b | Experimental | Drug: ZepatierParticipants 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 | Drug: Zepatier, Drug: RibavirinParticipants 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 | Drug: Zepatier, Drug: SofosbuvirParticipants 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 |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (10 listed)
- Plan to receive a multi-organ transplant
- Plan to receive a dual kidney transplant (including en bloc)
- Prior solid organ transplant
- Participating in another study that involves an intervention or investigational product
- Plan to receive a blood type incompatible kidney
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZepatierAlso: Fixed dose Grazoprevir /ElbasvirFixed dose Grazoprevir 100 mg/Elbasvir 50 mg by mouth daily for 12 weeks | Drug | Donor genotype 1a no resistance or 1b, Donor genotype 1a with resistance, Donor genotype 2 or 3 |
| RibavirinAlso: Rebetol, Copegus, Virazole, and RibasphereRibavirin 1200 mg/d (> 75 kg) or 1000 mg/d (< 75 kg) by mouth daily in two divided doses | Drug | Donor genotype 1a with resistance |
| SofosbuvirAlso: SovaldiSofosbuvir 400 mg daily | Drug | Donor genotype 2 or 3 |
Primary outcome
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
Time frame: 12 weeks after transplant
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.
6 secondary outcomes
Viral Response
Time frame: 12 weeks after completing treatment
Antibody Development
Time frame: 12 weeks
Number of Participants With Nonstructural Protein 5A (NS5A) Resistance Mutations in the HCV Population From the Deceased Donors
Time frame: Baseline
IP-10 Elevations
Time frame: 12 weeks
Kidney Function at 6 Months
Time frame: 6 months following transplantation
Kidney Function at 12 Months
Time frame: 12 months following transplantation
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Sep 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29507971Durand 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.
- Individual participant dataSharing planned: Yes. Peer reviewed publications
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Zepatier, Ribavirin and Sofosbuvir in people with End-Stage Renal Disease and Hepatitis C, run by Johns Hopkins University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Apr 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: 12 weeks after transplant). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02781649, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Sep 2018.