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MHH-HCV-NPM-Neuropsychiatric Manifestations of HCV-infection During and After Treatment With OBV/PTV/r and DSV

H

Hannover Medical School (MHH)

Status and phase

Terminated
Phase 4

Conditions

Hepatitis C, Chronic

Treatments

Drug: Placebo to match OBV/PTV/r and DSV
Drug: OBV/PTV/r and DSV

Study type

Interventional

Funder types

Other
Industry

Identifiers

NCT03003338
MHH-HCV-NPM
2015-004556-22 (EudraCT Number)

Details and patient eligibility

About

This is a 1:1 randomized double-blind Placebo-controlled moncenter Phase IV study to investigate whether a successful interferon-free treatment of HCV-infection with ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) in combination with dasabuvir (DSV) improves the patients' attention ability as compared to placebo as measured with the Att Test Sum Score change from baseline to week 12. A total of 30 patients with non-cirrhotic genotype 1b HCV infection will be randomly assigned to receive 12 weeks verum followed by 12 weeks Placebo (arm A) versus 12 weeks Placebo followed by 12 weeks verum (arm B). Patients will be followed up for 48 weeks.

Enrollment

5 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  1. Willing and able to provide written informed consent

  2. Male or female, age ≥18 years

  3. Chronic hepatitis C virus infection

  4. Fatigue Impact Scale Score (FIS) >45 and a sum score (Att Test Sum Score) >0.4 in the battery of attention tests applied.

  5. Female who is:

    • practicing total abstinence from sexual intercourse (minimum 1 complete menstrual cycle)

    • sexually active with female partners only

    • not of childbearing potential, defined as:

      • postmenopausal for at least 2 years (defined as amenorrheic for longer than 2 years, age appropriate, and confirmed by a follicle-stimulating hormone [FSH] level indicating a postmenopausal state), or
      • surgically sterile (defined as bilateral tubal ligation, bilateral oophorectomy or hysterectomy), or has a vasectomized partner (s);
    • of childbearing potential and sexually active with male partner(s):

      • currently using an effective method of birth control at the time of screening and
      • agree to practice highly effective methods of birth control while receiving study drugs and at least one effective method of birth control during the follow-up period (see section 4.3). (Note: Ethinylestradiol-containing hormonal contraceptives, including oral, injectable, implantable, patch and ring varieties, may not be used during study drug treatment.)
  6. Females of childbearing potential must have negative results for pregnancy tests performed:

    • at Screening on a serum specimen obtained within 28 days prior to initial study drug administration, and
    • on a urine sample obtained on Study Day 1 (prior to dosing).
  7. Males who are not surgically sterile and who are sexually active with female partner(s) of childbearing potential must agree to practice an effective form of birth control (see section 4.3) throughout the course of the study, starting with Study Day 1 and for 30 days after stopping study drug.

  8. Subject must be able to comply with the dosing instructions for study drug administration and be able to complete the study schedule of assessments.

  9. Body Mass Index (BMI) is > 17 to < 40 kg/m2. BMI is calculated as weight measured in kg divided by the square of height measured in meters (m).

  10. Confirmation of chronic genotype 1b HCV infection documented by the following:

    Positive for anti-HCV antibody or HCV RNA at least 6 months before Screening, and positive for HCV RNA and anti-HCV antibody at the time of Screening

  11. Per local standard practice, documented results of:

    • Index (APRI) ≤ 2 at Screening, or
    • FibroScan® result of < 12 kPa at Screening or
    • The absence of cirrhosis based on a liver biopsy within the last 36 months.
  12. HCV > RNA 1000 IU/ml at Screening

  13. Subject must be of generally good health as determined by the Investigator.

  14. Subject has not been treated with any investigational drug or device or any commercially available anti-HCV agents within 42 days of the Screening visit.

Exclusion criteria

  1. Any previous exposure to HCV protease inhibitors, HCV NS5A inhibitors or HCV polymerase inhibitors

  2. History of severe, life threatening or other significant sensitivity to any drug.

  3. Pregnant or nursing female or male with pregnant female partner

  4. Recent (within 6-months prior to study drug administration) history of drug or alcohol abuse that could preclude adherence to the protocol.

  5. Infection with hepatitis B virus (HBV; defined as HBsAg-positive) or human immunodeficiency virus (HIV)

  6. Use of any medication that are contraindicated for use with OBV/PTV/r and DSV within 2 weeks prior to study drug administration or 10 half-lives of the medication whichever is longer (see SmPC of OBV/PTV/r and DSV and section 4.4).

  7. Clinically-significant illness (other than HCV) or any other major medical disorder that, in the opinion of the investigator, may interfere with subject treatment, assessment or compliance with the protocol; subjects currently under evaluation for a potentially clinically-significant illness (other than HCV) are also excluded.

  8. Positive result of a urine drug screen at the Screening Visit for opiates, barbiturates, amphetamines, cocaine, benzodiazepines, phencyclidine, and propoxyphene.

  9. History of uncontrolled seizures, cancer (except basal cell carcinoma of the skin), or uncontrolled diabetes, as defined by a hemoglobin A1C level > 8.0% or other systemic diseases that affect directly the CNS and brain metabolites.

  10. Gastrointestinal disorder or post operative condition that could interfere with the absorption of the study drug (for example, gastric bypass or severe ulcerative colitis).

  11. Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, autoimmune hepatitis, alcoholic liver disease, Wilson's disease, α1 antitrypsin deficiency, cholangitis)

  12. Difficulty with blood collection and/or poor venous access for the purposes of phlebotomy.

  13. Clinical hepatic decompensation (i.e., clinical ascites, encephalopathy or variceal hemorrhage).

  14. Solid organ transplantation.

  15. Significant pulmonary disease or significant cardiac disease.

  16. Significant drug allergy (such as anaphylaxis or hepatotoxicity).

  17. Contraindications for MRI study

  18. Screening laboratory analyses show any of the following abnormal laboratory results:

    • Alanine aminotransferase (ALT) > 10 × upper limit of normal (ULN)
    • Aspartate aminotransferase (AST) > 10 × ULN
    • Calculated creatinine clearance (using CKD-EPI equal) < 30 mL/min
    • Albumin < lower limit of normal (LLN)
    • INR > 1.5
    • Hemoglobin < LLN
    • Platelets < 90,000 cells per mm3
    • Total bilirubin > 2.0 mg/dL
    • HCV RNA levels that are above the upper level of assay quantification
  19. Screening ECG with clinically significant abnormalities

  20. Consideration by the Investigator, for any reason, that the subject is an unsuitable candidate to receive the study medication

  21. Donation or loss of more than 400 ml blood within 2 months prior to Baseline/Day 1

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Crossover Assignment

Masking

Triple Blind

5 participants in 2 patient groups

OBV/PTV/r with DSV followed by placebo
Experimental group
Description:
OBV/PTV/r in combination with DSV for 12 weeks followed by 12 weeks matching placebo.
Treatment:
Drug: Placebo to match OBV/PTV/r and DSV
Drug: OBV/PTV/r and DSV
Placebo followed by OBV/PTV/r with DSV
Experimental group
Description:
Matching placebo for 12 weeks followed by 12 weeks OBV/PTV/r in combination with DSV.
Treatment:
Drug: Placebo to match OBV/PTV/r and DSV
Drug: OBV/PTV/r and DSV

Trial contacts and locations

1

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Central trial contact

Heiner Wedemeyer, Prof. Dr.; Markus Cornberg, Prof. Dr.

Data sourced from clinicaltrials.gov

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