Porphyria Cutanea TardaPhase 2NCT03118674
Harvoni Treatment Porphyria Cutanea Tarda
A Phase 2 study testing Harvoni in people with Porphyria Cutanea Tarda and Hepatitis C, run by Wake Forest University Health Sciences at 3 sites in United States.
Trial summary
In the medical literature there case reports that Harvoni improves symptoms in patients with PCT. However, this has never been systematically tested. Therefore, the purpose of this study is to assess whether Harvoni alone is an effective therapy of active PCT in patients with Chronic Hepatitis C. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Porphyria Cutanea Tarda, Hepatitis C
- What is being tested?
- Harvoni
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 3 sitesUnited States
- Study dates
- 6 Sep 2017to 4 Mar 2022
- Phase
- Phase 2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Willing and able to give informed consent
- ≥18 years of age
- Symptoms and signs consistent with PCT and well documented biochemical diagnosis (urinary total porphyrin excretion > 500 mcg/g Creatinine with HPLC pattern typical of PCT-predominance of 8- and 7-carboxyl porphyrins)
- Clinical diagnosis of PCT established by a study PI
- Chronic hepatitis C: HCV RNA positive and quantifiable in serum detected within 90 days of enrollment, and documented HCV genotypes 1,4, 5, or 6 for which Harvoni is an approved therapy.
- Women of child-bearing potential must be willing to avoid pregnancy and use an accepted and effective contraceptive method during treatment.
Who cannot join
- Women who are pregnant or who are breast-feeding
- Patients who have already started treatment of PCT with phlebotomy or low dose hydroxychloroquine or chloroquine, or who have been in such treatment in the past 30 days
- Patients who have already started another treatment regimen for CHC, or who have taken such treatment in the past 30 days
- HIV infection with CD4 counts at baseline less than 350/µL or with evidence of any active AIDS-defining illnesses
- Ongoing active alcohol abuse, defined as a history of drinking more than 25 drinks of alcohol per week during most weeks in the prior 4 months (History of prior, but not current alcohol abuse will NOT be grounds for exclusion because we seek to treat subjects with PCT and CHC of the type typically seen in clinical practice)
- Any ongoing active IV drug use
Show all 21Show fewer
- Patients who are taking amiodarone or who have taken amiodarone within 60 days prior to enrollment
- Patients who are taking, or within the prior 28 days have taken, rifampicin or St John's wort (Hypericum perforatum), both of which are P-gp inducers, which may significantly reduce the drug levels and therapeutic effects of Harvoni
- Uncontrolled diabetes (Hgb A1c >9.5% within 60 days prior to enrollment)
- Chronic hepatitis B
- Autoimmune hepatic liver injury-autoimmune hepatitis, primary biliary cholangitis/sclerosing cholangitis or overlap syndrome
- Alcoholic hepatitis
- Other metabolic disorders of the liver, e.g. Alpha 1 antitrypsin deficiency with ZZ Pi type, Wilson's disease
- Prior known or suspected drug-induced liver injury within 6 months of enrollment
- Known or suspected hepatocellular carcinoma
- On liver transplant list, or current MELD >12
- History of liver transplant
- Estimated GFR (Creatinine clearance) <30 mL/min (per Sofosbuvir being cleared by the kidney)
- Serum ALT or AST >10x normal
- Serum bilirubin >2 mg/dL (excluding patients with known or suspected Gilbert's syndrome)
- Any other comorbid condition, which, in the opinion of the investigator, precludes participation
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of Texas Medical Branch
Galveston, Texas, 77555
University of California, San Francisco
San Francisco, California, 94143
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
About this study
Official title: Newer Direct-Acting Anti-Viral Agents as Sole Therapy of Porphyria Cutanea Tarda in Subjects With Chronic Hepatitis C
In the medical literature there case reports that Harvoni improves symptoms in patients with PCT. However, this has never been systematically tested. Therefore, the purpose of this study is to assess whether Harvoni alone is an effective therapy of active PCT in patients with Chronic Hepatitis C.
Read the detailed description
This is a clinical trial, which means its purpose is to study an intervention or treatment. In this study all patients with PCT will be given a standard dose of Harvoni and monitored for two years. Currently there are two standard therapies for PCT, phlebotomies (removing certain amounts of blood at specific intervals), or low dose hydroxychloroquine (an oral pill). These treatments are used for patients with PCT whether or not they also have HCV. For patients with HCV however, we do not know whether treating the HCV first will also resolve the PCT symptoms. There will be an initial visit to determine whether participants are eligible to be in the study. If a participant is found to be eligible, he/she will be asked come to the study site once every month over the course of one year, and then once every 3 months for an additional year. There will be approximately 17 visits over the course of the whole study. At these visits the study doctors will check in with the participant and some blood and urine samples will be taken. Participants will not be charged for any of the lab tests that are being done as a part of this study alone. All participants in this study will receive the Harvoni pills at no cost to them.
- Conditions
- Porphyria Cutanea Tarda, Hepatitis C
- Being tested
- Harvoni
- Keywords
- Interventional, Open-label, PCT, Hepatitis C
- Medical subject headings
- Porphyria Cutanea Tarda, Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HarvoniDrug
Also called ledipasvir, 90 mg + sofosbuvir, 400 mg
One capsule of Harvoni/ ledipasvir, 90 mg + sofosbuvir, 400 mg administered daily for 8, 12, or 24 weeks
| Study group | Role | What they receive |
|---|---|---|
| Harvoni | Experimental | 1 tablet per day, oral, taken with or without food. 8 weeks for patients without cirrhosis, not previously treated with HCV GT1 and HCV rNA < 6 million IU/mL; 12 weeks for patients without cirrhosis; 24 weeks for patients with compensated cirrhosis Receives: Drug: Harvoni |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Resolution of Active PCT by 7 Months After Start of Therapy
Resolution of active PCT, defined as normalization of plasma porphyrins (less than 0.9 mcg/dL) by 7 months after start of therapy
Measured: 7 months
Secondary outcomes (3)
Time to Resolution of Active PCT
Time to resolution of active PCT, defined as cessation of any new blisters or bullae and normalization of plasma porphyrins
Measured: through study completion, an average of 1 year
Number of Participants With Complete Biochemical Remission of PCT
Defined as a decrease of the sum of urinary uro- and hepta-carboxyl porphyrins to less than 100 mcg/g creatinine and a normal urine porphyrin HPLC pattern defined as the total of highly carboxylated porphyrins (uro- and heptacarboxyl-porphyrins) being less than that of coproporphyrins, and the absence of a plasma fluorescence peak by fluorescence scanning
Measured: 12 Months
Number of Participants With Cure of CHC
Defined as no detectable HCV RNA at end of treatment and persisting for at least 12 weeks after end of treatment.
Measured: Up to 15 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2017
- Study start6 Sep 2017
- Primary completion4 Mar 2022
- Study completion4 Mar 2022
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 Porphyria Cutanea TardaStudies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- Gilead Sciences, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH)
- Responsible party
- Sponsor
- Investigators
- Herbert L Bonkovsky, MD, Study chair, Wake Forest University Health SciencesSean Rudnick, MD, Study director, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03118674
- Sponsor's protocol ID
- IRB00043341
- Other IDs
- U54DK083909
- Status last verified
- May 2023
- First submitted
- 13 Apr 2017
- Last updated
- 3 Jul 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bonkovsky HL, Rudnick SP, Ma CD, Overbey JR, Wang K, Faust D, Hallberg C, Hedstrom K, Naik H, Moghe A, Anderson KE. Ledipasvir/Sofosbuvir Is Effective as Sole Treatment of Porphyria Cutanea Tarda with Chronic Hepatitis C. Dig Dis Sci. 2023 Jun;68(6):2738-2746. doi: 10.1007/s10620-023-07859-8. Epub 2023 Feb 22.
PubMed 36811718
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Newer Direct-Acting Anti-Viral Agents as Sole Therapy of Porphyria Cutanea Tarda in Subjects With Chronic Hepatitis C
- ClinicalTrials.gov ID
- NCT03118674
- Acronym / sponsor ID
- IRB00043341
- Conditions
- Porphyria Cutanea Tarda, Hepatitis C
- Keywords
- Interventional, Open-label, PCT, Hepatitis C
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Collaborators
- Gilead Sciences, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH)
- Study start
- 6 Sep 2017 (actual)
- Primary completion
- 4 Mar 2022 (actual)
- Study completion
- 4 Mar 2022 (actual)
- First posted
- 18 Apr 2017 (actual)
- Results
- Posted 3 Jul 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In the medical literature there case reports that Harvoni improves symptoms in patients with PCT. However, this has never been systematically tested. Therefore, the purpose of this study is to assess whether Harvoni alone is an effective therapy of active PCT in patients with Chronic Hepatitis C.
Detailed description
This is a clinical trial, which means its purpose is to study an intervention or treatment. In this study all patients with PCT will be given a standard dose of Harvoni and monitored for two years. Currently there are two standard therapies for PCT, phlebotomies (removing certain amounts of blood at specific intervals), or low dose hydroxychloroquine (an oral pill). These treatments are used for patients with PCT whether or not they also have HCV. For patients with HCV however, we do not know whether treating the HCV first will also resolve the PCT symptoms. There will be an initial visit to determine whether participants are eligible to be in the study. If a participant is found to be eligible, he/she will be asked come to the study site once every month over the course of one year, and then once every 3 months for an additional year. There will be approximately 17 visits over the course of the whole study. At these visits the study doctors will check in with the participant and some blood and urine samples will be taken. Participants will not be charged for any of the lab tests that are being done as a part of this study alone. All participants in this study will receive the Harvoni pills at no cost to them.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Harvoni | Experimental | Drug: Harvoni1 tablet per day, oral, taken with or without food. 8 weeks for patients without cirrhosis, not previously treated with HCV GT1 and HCV rNA < 6 million IU/mL; 12 weeks for patients without cirrhosis; 24 weeks for patients with compensated cirrhosis |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Willing and able to give informed consent
- ≥18 years of age
- Symptoms and signs consistent with PCT and well documented biochemical diagnosis (urinary total porphyrin excretion > 500 mcg/g Creatinine with HPLC pattern typical of PCT-predominance of 8- and 7-carboxyl porphyrins)
- Clinical diagnosis of PCT established by a study PI
- Chronic hepatitis C: HCV RNA positive and quantifiable in serum detected within 90 days of enrollment, and documented HCV genotypes 1,4, 5, or 6 for which Harvoni is an approved therapy.
Key exclusion criteria (21 listed)
- Women who are pregnant or who are breast-feeding
- Patients who have already started treatment of PCT with phlebotomy or low dose hydroxychloroquine or chloroquine, or who have been in such treatment in the past 30 days
- Patients who have already started another treatment regimen for CHC, or who have taken such treatment in the past 30 days
- HIV infection with CD4 counts at baseline less than 350/µL or with evidence of any active AIDS-defining illnesses
- Ongoing active alcohol abuse, defined as a history of drinking more than 25 drinks of alcohol per week during most weeks in the prior 4 months (History of prior, but not current alcohol abuse will NOT be grounds for exclusion because we seek to treat subjects with PCT and CHC of the type typically seen in clinical practice)
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 |
|---|---|---|
| HarvoniAlso: ledipasvir, 90 mg + sofosbuvir, 400 mgOne capsule of Harvoni/ ledipasvir, 90 mg + sofosbuvir, 400 mg administered daily for 8, 12, or 24 weeks | Drug | Harvoni |
Primary outcome
Number of Participants With Resolution of Active PCT by 7 Months After Start of Therapy
Time frame: 7 months
Resolution of active PCT, defined as normalization of plasma porphyrins (less than 0.9 mcg/dL) by 7 months after start of therapy
3 secondary outcomes
Time to Resolution of Active PCT
Time frame: through study completion, an average of 1 year
Number of Participants With Complete Biochemical Remission of PCT
Time frame: 12 Months
Number of Participants With Cure of CHC
Time frame: Up to 15 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36811718Bonkovsky HL, Rudnick SP, Ma CD, Overbey JR, Wang K, Faust D, Hallberg C, Hedstrom K, Naik H, Moghe A, Anderson KE. Ledipasvir/Sofosbuvir Is Effective as Sole Treatment of Porphyria Cutanea Tarda with Chronic Hepatitis C. Dig Dis Sci. 2023 Jun;68(6):2738-2746. doi: 10.1007/s10620-023-07859-8. Epub 2023 Feb 22.
- Porphyrias Consortium WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Porphyria Cutanea Tarda
RecruitingObservational study
Longitudinal Study of the Porphyrias
Acute Porphyrias, Cutaneous Porphyrias
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.
Herbert L Bonkovsky, MD study chair
Wake Forest University Health Sciences
Sean Rudnick, MD study director
Wake Forest University Health Sciences
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Harvoni in people with Porphyria Cutanea Tarda and Hepatitis C, run by Wake Forest University Health Sciences at 3 sites 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 6 inclusion and 21 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 3 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 3 Jul 2023). 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 Resolution of Active PCT by 7 Months After Start of Therapy (time frame: 7 months). 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 NCT03118674, 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 3 Jul 2023.