Porphyria Cutanea Tarda, Hepatitis C
Conditions
Keywords
Interventional, Open-label, PCT, Hepatitis C
Brief 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.
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.
Interventions
DRUGHarvoni
One capsule of Harvoni/ ledipasvir, 90 mg + sofosbuvir, 400 mg administered daily for 8, 12, or 24 weeks
Sponsors
Gilead Sciences
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Institutes of Health (NIH)
Wake Forest University Health Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Willing and able to give informed consent 2. ≥18 years of age 3. 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) 4. Clinical diagnosis of PCT established by a study PI 5. 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. 6. Women of child-bearing potential must be willing to avoid pregnancy and use an accepted and effective contraceptive method during treatment.
Exclusion criteria
1. Women who are pregnant or who are breast-feeding 2. 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 3. Patients who have already started another treatment regimen for CHC, or who have taken such treatment in the past 30 days 4. HIV infection with CD4 counts at baseline less than 350/µL or with evidence of any active AIDS-defining illnesses 5. 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) 6. Any ongoing active IV drug use 7. Patients who are taking amiodarone or who have taken amiodarone within 60 days prior to enrollment 8. 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 9. Uncontrolled diabetes (Hgb A1c \>9.5% within 60 days prior to enrollment) 10. Chronic hepatitis B 11. Autoimmune hepatic liver injury-autoimmune hepatitis, primary biliary cholangitis/sclerosing cholangitis or overlap syndrome 12. Alcoholic hepatitis 13. Other metabolic disorders of the liver, e.g. Alpha 1 antitrypsin deficiency with ZZ Pi type, Wilson's disease 14. Prior known or suspected drug-induced liver injury within 6 months of enrollment 15. Known or suspected hepatocellular carcinoma 16. On liver transplant list, or current MELD \>12 17. History of liver transplant 18. Estimated GFR (Creatinine clearance) \<30 mL/min (per Sofosbuvir being cleared by the kidney) 19. Serum ALT or AST \>10x normal 20. Serum bilirubin \>2 mg/dL (excluding patients with known or suspected Gilbert's syndrome) 21. Any other comorbid condition, which, in the opinion of the investigator, precludes participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Resolution of Active PCT by 7 Months After Start of Therapy | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Resolution of Active PCT | through study completion, an average of 1 year | Time to resolution of active PCT, defined as cessation of any new blisters or bullae and normalization of plasma porphyrins |
| Number of Participants With Complete Biochemical Remission of PCT | 12 Months | 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 |
| Number of Participants With Cure of CHC | Up to 15 months | Defined as no detectable HCV RNA at end of treatment and persisting for at least 12 weeks after end of treatment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Harvoni 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
Harvoni: One capsule of Harvoni/ ledipasvir, 90 mg + sofosbuvir, 400 mg administered daily for 8, 12, or 24 weeks | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Screen Faliure | 8 |
| Overall Study | Withdrawal by Subject | 5 |
Baseline characteristics
| Characteristic | Harvoni |
|---|---|
| Age, Continuous | 58.9 years STANDARD_DEVIATION 4.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 15 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 15 |
| other Total, other adverse events | 1 / 15 |
| serious Total, serious adverse events | 0 / 15 |
Outcome results
Primary
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
Time frame: 7 months
Population: 9 observations collected at 7 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Harvoni | Number of Participants With Resolution of Active PCT by 7 Months After Start of Therapy | 9 Participants |
Secondary
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
Time frame: 12 Months
Population: 6 Observations collected at 12 Months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Harvoni | Number of Participants With Complete Biochemical Remission of PCT | 5 Participants |
Secondary
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.
Time frame: Up to 15 months
Population: 2 participants lost of follow up, 1 participant left the study after 4 weeks of dosing
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Harvoni | Number of Participants With Cure of CHC | 11 Participants |
Secondary
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
Time frame: through study completion, an average of 1 year
Population: Observations for 6 participants collected at through study completion, an average of 1 year
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Harvoni | Time to Resolution of Active PCT | 240 days |