Clinical trial NCT03118674: Harvoni Treatment Porphyria Cutanea Tarda
Official title: Newer Direct-Acting Anti-Viral Agents as Sole Therapy of Porphyria Cutanea Tarda in Subjects With Chronic Hepatitis C
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Porphyria Cutanea Tarda
Hepatitis C
Keywords: Interventional, Open-label, PCT, Hepatitis C
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: Gilead Sciences
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: National Institutes of Health (NIH)
First posted: 2017-04-18
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Resolution of Active PCT by 7 Months After Start of Therapy
timeFrame: 7 months
Secondary outcomes:
measure: Time to Resolution of Active PCT
timeFrame: through study completion, an average of 1 year
measure: Number of Participants With Complete Biochemical Remission of PCT
timeFrame: 12 Months
measure: Number of Participants With Cure of CHC
timeFrame: Up to 15 months
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
Study officials:
affiliation: Wake Forest University Health Sciences
name: Herbert L Bonkovsky, MD
role: STUDY_CHAIR
affiliation: Wake Forest University Health Sciences
name: Sean Rudnick, MD
role: STUDY_DIRECTOR
References: