Study of ABT-267 in Treatment Naive Hepatitis C Virus (HCV) Genotype 1 Infected Subjects

NCT01314261 | Completed Phase 2 Results

• 1 other identifier: M12-114
• Study Type: interventional
• Target: 37
• Locations: 2 countries
• Sites: 11

Brief Summary

The purpose of this study was to assess the safety, pharmacokinetics, and 4-week rapid virologic response (RVR) of 3 different doses of ABT-267 (also known as ombitasvir) in combination with pegylated interferon/ribavirin (pegIFN/RBV) compared with pegIFN/RBV alone (ABT-267 placebo) in treatment naïve, hepatitis C virus (HCV), genotype 1-infected participants.

Conditions

Chronic Hepatitis C; Hepatitis C Virus (HCV) Infection

Outcome Measures

Primary Outcomes (6)

• Percentage of Participants With 4-week Rapid Virologic Response (RVR)

  Plasma hepatitis C virus ribonucleic acid (HCV RNA) levels (measured in IU/mL) were determined for each sample using a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Rapid virologic response was defined as HCV RNA levels \< the lower limit of detection (\< 15 IU/mL) at Week 4. Data are reported as percentage of participants with RVR.

  Week 4

• Maximum Plasma Concentration (Cmax) of ABT-267

  Blood samples were collected immediately prior to morning dose (time 0 hours); 2, 4, 6, and 8 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose). The samples were analyzed for the concentration of ABT-267 using validated analytical methods. The maximum plasma concentration (Cmax; measured in ng/mL) is the highest concentration that a drug achieves in the plasma after administration in a dosing interval. The Cmax of ABT-267 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation.

  Immediately prior to morning dose (time 0 hours); 2, 4, 6, and 8 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose)

• Time to Maximum Plasma Concentration (Tmax) of ABT-267

  Blood samples were collected immediately prior to morning dose (time 0 hours); 2, 4, 6, and 8 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose). The samples were analyzed for the concentration of ABT-267 using validated analytical methods. The time to maximum plasma concentration (Tmax; measured in hours) is the time it takes for a drug to achieve Cmax. The Tmax of ABT-267 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation.

  Immediately prior to morning dose (time 0 hours); 2, 4, 6, and 8 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose)

• Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24) Post-dose of ABT-267

  Blood samples were collected immediately prior to morning dose (time 0 hours); 2, 4, 6, and 8 hours after the morning dose on Day 1; prior to dose on Day 2 (24 hours after Day 1 dose); and at each subsequent study visit. The samples were analyzed for the concentration of ABT-267 using validated analytical methods. The area under the plasma concentration -time curve (AUC; measured in ng\*hr/mL) is a method of measurement of the total exposure of a drug in blood plasma. The AUC24 of ABT-267 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation.

  Immediately prior to morning dose (time 0 hours); 2, 4, 6, and 8 hours after the morning dose on Day 1; prior to dose on Day 2 (24 hours after Day 1 dose); and at each subsequent study visit up to Week 12

• Plasma Concentrations of Ribavirin (RBV)

  Blood samples were collected at each study visit from Week 1 to Week 12. The samples were analyzed for the concentration of RBV (measured in ng/mL) using validated analytical methods and RBV concentrations in plasma were summarized at each visit. Data are reported as the median (range).

  At each study visit from Week 1 to Week 12

• Serum Concentrations of Pegylated Interferon (pegIFN)

  Blood samples were collected at each study visit from Week 1 to Week 12. The samples were analyzed for the concentration of pegIFN (measured in ng/mL) using validated analytical methods and pegIFN concentrations in serum were summarized at each visit. Data are reported as the median (range).

  At each study visit from Week 1 to Week 12

Secondary Outcomes (6)

• Percentage of Participants With Partial Early Virologic Response (pEVR)

  Baseline and Week 12

• Percentage of Participants With Complete Early Virologic Response (cEVR)

  Week 12

• Percentage of Participants With Sustained Virologic Response 12 Weeks (SVR12) Post-pegylated Interferon/Ribavirin (pegIFN/RBV) Dosing

  12 weeks after the last dose of pegIFN/RBV

• Percentage of Participants With Sustained Virologic Response 24 Weeks (SVR24) Post-pegylated Interferon/Ribavirin (pegIFN/RBV) Dosing

  24 weeks after the last dose of pegIFN/RBV

• Median Time to Suppression of Hepatitis C Virus Ribonucleic Acid (HCV RNA)

  Approximately 12 weeks

Study Arms (4)

ABT-267 (5 mg) once daily + pegIFN/RBV

EXPERIMENTAL

Participants were given 5 mg ABT-267 once daily in combination with pegylated interferon/ribavirin (pegIFN/RBV) for 12 weeks, followed by 36 weeks of pegIFN/RBV treatment alone. Pegylated interferon was dosed 180 µg subcutaneously once a week. Ribavirin was dosed 1000 or 1200 mg daily divided twice a day.

Drug: ABT-267; Drug: Pegylated interferon (pegIFN); Drug: Ribavirin (RBV)

ABT-267 (50 mg) once daily + pegIFN/RBV

EXPERIMENTAL

Participants were given 50 mg ABT-267 once daily in combination with pegylated interferon/ribavirin (pegIFN/RBV) for 12 weeks, followed by 36 weeks of pegIFN/RBV treatment alone. Pegylated interferon was dosed 180 µg subcutaneously once a week. Ribavirin was dosed 1000 or 1200 mg daily divided twice a day.

Drug: ABT-267; Drug: Pegylated interferon (pegIFN); Drug: Ribavirin (RBV)

ABT-267 (200 mg) once daily + pegIFN/RBV

EXPERIMENTAL

Participants were given 200 mg ABT-267 once daily in combination with pegylated interferon/ribavirin (pegIFN/RBV) for 12 weeks, followed by 36 weeks of pegIFN/RBV treatment alone. Pegylated interferon was dosed 180 µg subcutaneously once a week. Ribavirin was dosed 1000 or 1200 mg daily divided twice a day.

Drug: ABT-267; Drug: Pegylated interferon (pegIFN); Drug: Ribavirin (RBV)

Placebo + pegIFN/RBV

PLACEBO COMPARATOR

Participants were given matching placebo to ABT-267 once daily in combination with pegIFN/RBV for 12 weeks, followed by 36 weeks of pegIFN/RBV treatment alone. Pegylated interferon was dosed 180 µg subcutaneously once a week. Ribavirin was dosed 1000 or 1200 mg daily divided twice a day.

Drug: Pegylated interferon (pegIFN); Drug: Ribavirin (RBV); Other: Placebo for ABT-267

Interventions

ABT-267 DRUG

5 mg or 25 mg tablets

Also known as: Ombitasvir

ABT-267 (200 mg) once daily + pegIFN/RBV; ABT-267 (5 mg) once daily + pegIFN/RBV; ABT-267 (50 mg) once daily + pegIFN/RBV

Pegylated interferon (pegIFN) DRUG

Syringe, 180 µg/0.5 mL for subcutaneous injections administered weekly

ABT-267 (200 mg) once daily + pegIFN/RBV; ABT-267 (5 mg) once daily + pegIFN/RBV; ABT-267 (50 mg) once daily + pegIFN/RBV; Placebo + pegIFN/RBV

Ribavirin (RBV) DRUG

200 mg tablet dosed at 1000 or 1200 mg daily divided twice a day

ABT-267 (200 mg) once daily + pegIFN/RBV; ABT-267 (5 mg) once daily + pegIFN/RBV; ABT-267 (50 mg) once daily + pegIFN/RBV; Placebo + pegIFN/RBV

Placebo for ABT-267 OTHER

Participants received matching placebo tablet at each dose level for ABT-267.

Placebo + pegIFN/RBV

Eligibility Criteria

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

You may qualify if:

• Treatment naïve participants
• Females must be either postmenopausal for at least 2 years or surgically sterile
• Males must be surgically sterile or practicing specific forms of birth control
• Chronic hepatitis C virus (HCV), genotype-1 infected participants
• Documented FibroTest score in combination with an Aspartate Aminotransferase to Platelet Ratio Index (APRI), or a liver biopsy within the last 12 months to document absence of cirrhosis

You may not qualify if:

• Pregnant or breastfeeding female
• Use of any medications contraindicated for use with pegylated interferon(pegIFN) or ribavirin (RBV) 2 weeks prior to study drug administration or 10 half-lives, whichever is longer
• Clinically significant cardiac, respiratory (except mild asthma), renal, gastrointestinal, hematologic, neurologic disease, or any uncontrolled medical illness or psychiatric disease or disorder
• Current or past clinical evidence of cirrhosis or bridging fibrosis
• Abnormal screening laboratory results

Sponsors & Collaborators

• AbbVie (prior sponsor, Abbott): lead

Study Sites (11)

Site Reference ID/Investigator# 56623

Birmingham, Alabama, 35215, United States

Location

Site Reference ID/Investigator# 48476

Los Angeles, California, 90048, United States

Location

Site Reference ID/Investigator# 51345

Orlando, Florida, 32809, United States

Location

Site Reference ID/Investigator# 51498

Honolulu, Hawaii, 96814, United States

Location

Site Reference ID/Investigator# 48473

Indianapolis, Indiana, 46202, United States

Location

Site Reference ID/Investigator# 52782

Kansas City, Missouri, 64131, United States

Location

Site Reference ID/Investigator# 48471

Houston, Texas, 77030, United States

Location

Site Reference ID/Investigator# 48474

San Antonio, Texas, 78215, United States

Location

Site Reference ID/Investigator# 48477

Fairfax, Virginia, 22031, United States

Location

Site Reference ID/Investigator# 48472

Seattle, Washington, 98101, United States

Location

Site Reference ID/Investigator# 48483

San Juan, 00927, Puerto Rico

Location

Related Publications (1)

• Mensing S, Polepally AR, Konig D, Khatri A, Liu W, Podsadecki TJ, Awni WM, Menon RM, Dutta S. Population Pharmacokinetics of Paritaprevir, Ombitasvir, Dasabuvir, Ritonavir, and Ribavirin in Patients with Hepatitis C Virus Genotype 1 Infection: Combined Analysis from 9 Phase 1b/2 Studies. AAPS J. 2016 Jan;18(1):270-80. doi: 10.1208/s12248-015-9846-1. Epub 2015 Nov 23.

  PMID: 26597291 BACKGROUND

Related Links

• Related Info

MeSH Terms

Conditions

Hepatitis C, Chronic; Hepatitis C; Infections

Interventions

ombitasvir; Ribavirin

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; 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

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie (prior sponsor, Abbott)

800-633-9110

Study Officials

• Armen Asatryan, MD

  AbbVie

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2011
• First Posted: March 14, 2011
• Study Start: March 1, 2011
• Primary Completion: January 1, 2012
• Study Completion: February 1, 2013
• Last Updated: July 2, 2018
• Results First Posted: January 26, 2015

Record last verified: 2015-01

Locations

US (10); PR (1)