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Harvoni Treatment Porphyria Cutanea Tarda

Primary Purpose

Porphyria Cutanea Tarda, Hepatitis C

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Harvoni
Sponsored by
Wake Forest University Health Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Porphyria Cutanea Tarda focused on measuring Interventional, Open-label, PCT, Hepatitis C

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of California, San Francisco
  • Wake Forest University Health Sciences
  • University of Texas Medical Branch

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Harvoni

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
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
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.

Full Information

First Posted
April 13, 2017
Last Updated
June 14, 2023
Sponsor
Wake Forest University Health Sciences
Collaborators
Gilead Sciences, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH)
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1. Study Identification

Unique Protocol Identification Number
NCT03118674
Brief Title
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

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
September 6, 2017 (Actual)
Primary Completion Date
March 4, 2022 (Actual)
Study Completion Date
March 4, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Wake Forest University Health Sciences
Collaborators
Gilead Sciences, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH)

4. Oversight

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
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Porphyria Cutanea Tarda, Hepatitis C
Keywords
Interventional, Open-label, PCT, Hepatitis C

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
23 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Harvoni
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Harvoni
Other Intervention Name(s)
ledipasvir, 90 mg + sofosbuvir, 400 mg
Intervention Description
One capsule of Harvoni/ ledipasvir, 90 mg + sofosbuvir, 400 mg administered daily for 8, 12, or 24 weeks
Primary Outcome Measure Information:
Title
Number of Participants With Resolution of Active PCT by 7 Months After Start of Therapy
Description
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
Secondary Outcome Measure Information:
Title
Time to Resolution of Active PCT
Description
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
Title
Number of Participants With Complete Biochemical Remission of PCT
Description
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
Title
Number of Participants With Cure of CHC
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria 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. Exclusion Criteria 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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Herbert L Bonkovsky, MD
Organizational Affiliation
Wake Forest University Health Sciences
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Sean Rudnick, MD
Organizational Affiliation
Wake Forest University Health Sciences
Official's Role
Study Director
Facility Information:
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Wake Forest University Health Sciences
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
University of Texas Medical Branch
City
Galveston
State/Province
Texas
ZIP/Postal Code
77555
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://www.rarediseasesnetwork.org/cms/porphyrias/Studies
Description
Porphyrias Consortium Website

Learn more about this trial

Harvoni Treatment Porphyria Cutanea Tarda

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