Harvoni Treatment Porphyria Cutanea Tarda

Hepatitis C Clinical Trial

Official title:

Newer Direct-Acting Anti-Viral Agents as Sole Therapy of Porphyria Cutanea Tarda in Subjects With Chronic Hepatitis C

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03118674
• Other study ID #: IRB00043341
• Secondary ID: U54DK083909
• Status: Completed
• Phase: Phase 2
• Start date: September 6, 2017
• Est. completion date: March 4, 2022

Study information

• Verified date: May 2023
• Source: Wake Forest University Health Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: March 4, 2022
• Est. primary completion date: March 4, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Porphyria Cutanea Tarda
• Porphyria, Erythropoietic
• Porphyrias

Intervention

Drug:
• Harvoni
One capsule of Harvoni/ ledipasvir, 90 mg + sofosbuvir, 400 mg administered daily for 8, 12, or 24 weeks

Locations

Country	Name	City	State
United States	University of Texas Medical Branch	Galveston	Texas
United States	University of California, San Francisco	San Francisco	California
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (4)

Lead Sponsor	Collaborator
Wake Forest University Health Sciences	Gilead Sciences, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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	7 months
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	through study completion, an average of 1 year
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	12 Months
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.	Up to 15 months

External Links

•   Porphyrias Consortium Website