Harvoni Treatment Porphyria Cutanea Tarda

• ClinicalTrials.gov Identifier: NCT03118674
• Recruitment Status: Recruiting
• First Posted: April 18, 2017
• Last Update Posted: July 24, 2020
• Sponsor: Wake Forest University Health Sciences
• Collaborators: Gilead Sciences; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Institutes of Health (NIH)
• Information provided by (Responsible Party): Wake Forest University Health Sciences

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Porphyria Cutanea Tarda; Hepatitis C	Drug: Harvoni	Phase 2

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

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 49 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Newer Direct-Acting Anti-Viral Agents as Sole Therapy of Porphyria Cutanea Tarda in Subjects With Chronic Hepatitis C
• Actual Study Start Date: September 6, 2017
• Estimated Primary Completion Date: August 30, 2023
• Estimated Study Completion Date: August 30, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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	Drug: Harvoni; One capsule of Harvoni/ ledipasvir, 90 mg + sofosbuvir, 400 mg administered daily for 8, 12, or 24 weeks; Other Name: ledipasvir, 90 mg + sofosbuvir, 400 mg

Outcome Measures

Primary Outcome Measures :

1. 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

Secondary Outcome Measures :

1. Time to resolution of active PCT [ Time Frame: 12 months ]
   Time to resolution of active PCT, defined as cessation of any new blisters or bullae and normalization of plasma porphyrins

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Hetanshi Naik, MS; 212-241-7699; hetanshi.naik@mssm.edu

Contact: Dee Faust; 336-713-1442; delannin@wakehealth.edu

Locations

United States, Alabama

McGuire, Brendan M. MD; Withdrawn

Birmingham, Alabama, United States, 35294

United States, California

University of California, San Francisco; Recruiting

San Francisco, California, United States, 94143

Contact: Yuvraaj Kapoor, MS 415-476-8405 yuvraaj.kapoor@ucsf.edu

Principal Investigator: D. Montgomery Bissell, MD

United States, Florida

University of Miami Liver center; Withdrawn

Miami, Florida, United States, 33136

United States, New York

Icahn School of Medicine at Mount Sinai; Withdrawn

New York, New York, United States, 10029

United States, North Carolina

Wake Forest University Health Sciences; Recruiting

Winston-Salem, North Carolina, United States, 27157

Contact: Dee Faust 336-713-1442 delannin@wakehealth.edu

Principal Investigator: Herbert L Bonkovsky, MD

Sub-Investigator: Sean Rudnick, MD

United States, Pennsylvania

Kimmel School of Medicine of T Jefferson University; Withdrawn

Philadelphia, Pennsylvania, United States, 19085

United States, Texas

University of Texas Medical Branch; Recruiting

Galveston, Texas, United States, 77555

Contact: Csilla Hallberg, MD 409-772-6287 challberg@utmb.edu

Principal Investigator: Kar Anderson, MD

United States, Utah

University of Utah; Withdrawn

Salt Lake City, Utah, United States, 84132

Sponsors and Collaborators

Wake Forest University Health Sciences

Gilead Sciences

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

National Institutes of Health (NIH)

Investigators

• Study Chair: Herbert L Bonkovsky, MD; Wake Forest University Health Sciences
• Study Director: Sean Rudnick, MD; Wake Forest University Health Sciences

More Information

Additional Information:

Porphyrias Consortium Website 

• Responsible Party: Wake Forest University Health Sciences
• ClinicalTrials.gov Identifier: NCT03118674
• Other Study ID Numbers: IRB00043341; U54DK083909 ( U.S. NIH Grant/Contract )
• First Posted: April 18, 2017
• Last Update Posted: July 24, 2020
• Last Verified: May 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Wake Forest University Health Sciences:

Interventional, Open-label, PCT, Hepatitis C

Additional relevant MeSH terms:

Hepatitis A; Hepatitis C; Hepatitis; Porphyria Cutanea Tarda; Porphyrias, Hepatic; Porphyria, Erythropoietic; Porphyrias; Liver Diseases; Digestive System Diseases; Hepatitis, Viral, Human; Virus Diseases; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Flaviviridae Infections; Metabolic Diseases; Skin Diseases, Genetic; Genetic Diseases, Inborn; Skin Diseases; Sofosbuvir; Ledipasvir, sofosbuvir drug combination; Ledipasvir; Antiviral Agents; Anti-Infective Agents