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

NCT03003338 | Terminated Phase 4

• 2 other identifiers: MHH-HCV-NPM2015-004556-22
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hepatitis C, Chronic

Keywords

chronic HCV Genotype 1b infection; HCV RNA; OBV/PTV/r in combination with DSV; neuropsychiatric manifestations

Outcome Measures

Primary Outcomes (1)

• Change in the Attention Test Battery Sum Score (Att Test Sum Score) at week 12 (12 weeks minus baseline)

  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.

  12 weeks

Secondary Outcomes (30)

• Efficacy of treatment with OBV/PTV/r in combination with DSV for 12w in patients with chronic genotype 1b HCV infection as measured by the proportion of subjects with sustained viral response at FU 12 after discontinuation of therapy

  Baseline and FU12

• Efficacy of treatment with OBV/PTV/r in combination with DSV for 12w in patients with chronic genotype 1b HCV infection as measured by the proportion of subjects with sustained viral response at FU 24 after discontinuation of therapy

  Baseline and FU 24

• Efficacy of treatment with OBV/PTV/r in combination with DSV for 12w in patients with chronic genotype 1b HCV infection as measured by the proportion of subjects with sustained viral response at FU48 after discontinuation of therapy

  Baseline and FU 48

• Change in FIS at Treatment week 12 after Treatment discontinuation

  Baseline and week 12

• Change in FIS at Treatment at 12 weeks of follow-up after Treatment discontinuation

  Baseline and 12 weeks of follow-up

Other Outcomes (5)

• HCV-specific T cell responses

  Baseline and 48 weeks follow-up

• HCV-specific T cell responses

  Baseline and 48 weeks follow-up

• Relationship between NK cell phenotype and function

  Baseline and 48 weeks follow-up

Study Arms (2)

OBV/PTV/r with DSV followed by placebo

EXPERIMENTAL

OBV/PTV/r in combination with DSV for 12 weeks followed by 12 weeks matching placebo.

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

Placebo followed by OBV/PTV/r with DSV

EXPERIMENTAL

Matching placebo for 12 weeks followed by 12 weeks OBV/PTV/r in combination with DSV.

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

Interventions

OBV/PTV/r and DSV DRUG

OBV/PTV/r (12.5 mg/ 75 mg/ 50 mg) in combination with DSV (250 mg): Two tablets of OBV/PTV/r in the morning and one tablet of DSV in the morning and one tablet of DSV in the evening orally with a meal without regard to fat or calorie content.

Also known as: Viekirax and Exviera

OBV/PTV/r with DSV followed by placebo; Placebo followed by OBV/PTV/r with DSV

Placebo to match OBV/PTV/r and DSV DRUG

Placebo to match OBV/PTV/r and DSV

OBV/PTV/r with DSV followed by placebo; Placebo followed by OBV/PTV/r with DSV

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide written informed consent
• Male or female, age ≥18 years
• Chronic hepatitis C virus infection
• Fatigue Impact Scale Score (FIS) \>45 and a sum score (Att Test Sum Score) \>0.4 in the battery of attention tests applied.
• 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.)
• 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

You may not qualify if:

• Any previous exposure to HCV protease inhibitors, HCV NS5A inhibitors or HCV polymerase inhibitors
• History of severe, life threatening or other significant sensitivity to any drug.
• Pregnant or nursing female or male with pregnant female partner
• Recent (within 6-months prior to study drug administration) history of drug or alcohol abuse that could preclude adherence to the protocol.
• Infection with hepatitis B virus (HBV; defined as HBsAg-positive) or human immunodeficiency virus (HIV)
• 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).
• 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.
• Positive result of a urine drug screen at the Screening Visit for opiates, barbiturates, amphetamines, cocaine, benzodiazepines, phencyclidine, and propoxyphene.
• 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.
• Gastrointestinal disorder or post operative condition that could interfere with the absorption of the study drug (for example, gastric bypass or severe ulcerative colitis).
• Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, autoimmune hepatitis, alcoholic liver disease, Wilson's disease, α1 antitrypsin deficiency, cholangitis)
• Difficulty with blood collection and/or poor venous access for the purposes of phlebotomy.
• Clinical hepatic decompensation (i.e., clinical ascites, encephalopathy or variceal hemorrhage).
• Solid organ transplantation.
• Significant pulmonary disease or significant cardiac disease.

Sponsors & Collaborators

• Hannover Medical School: lead
• AbbVie: collaborator

Study Sites (1)

Hannover Medical School

Hanover, 30625, Germany

Location

MeSH Terms

Conditions

Hepatitis C, Chronic

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Heiner Wedemeyer, Prof. Dr.

  Hannover Medical School, Department of Gastroenterology, Hepatology and Endocrinology, Carl-Neuberg-Str. 1, 30625 Hannover, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2016
• First Posted: December 28, 2016
• Study Start: October 24, 2017
• Primary Completion: October 22, 2018
• Study Completion: October 22, 2018
• Last Updated: August 14, 2023

Record last verified: 2023-08

Locations

DE (1)