Efficacy and Safety Study of Pegylated Interferon Lambda-1a With Ribavirin and Daclatasvir, to Treat naïve Subjects With Chronic HCV Genotypes 1, 2, 3, and 4 Who Are Co-infected With HIV

NCT01866930 | Terminated Phase 3 Results

• 2 other identifiers: AI452-0322012-003280-22
• Study Type: interventional
• Target: 453
• Locations: 12 countries
• Sites: 63

Brief Summary

To evaluate Sustained Virologic Response at post treatment Week 12 (SVR12)following treatment with Lambda/RBV/DCV in chronic HCV GT-1, -2, -3 or -4 subjects co-infected with HIV-1

Conditions

Chronic Hepatitis C Infection

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Sustained Virologic Response at Post-treatment Week 12 (SVR12)

  SVR12 was defined as HCV RNA less than lower limit of quantification (\< LLOQ) (25 IU/mL; target detected or not detected) at follow-up week 12.

  Follow-up week 12

Secondary Outcomes (12)

• Number of Participants With Rapid Virologic Response (RVR) and Extended Rapid Virologic Response (eRVR)

  Treatment weeks 4 and 12

• Number of Subjects With Sustained Virologic Response at Post-treatment Week 24 (SVR24)

  Follow-up week 24

• Number of Participants With Treatment Emergent Cytopenic Abnormalities

  After Day 1 to end of treatment; up to Weeks 24 or 48

• Number of Participants With On-treatment IFN-associated Flu-like or Musculoskeletal Symptoms

  After Day 1 to end of treatment; up to Weeks 24 or 48

• Number of Participants Who Died or Experienced Severe Adverse Events (SAEs), Dose Reductions of Lambda or Discontinuation Due to Adverse Events (AEs)

  After Day 1 to end of treatment; up to Weeks 24 or 48

Study Arms (2)

Cohort A: GT-2 or -3 HCV Treatment Naïve Subjects

EXPERIMENTAL

Pegylated Interferon Lambda 180 µg solution, injection subcutaneously once weekly for 24 weeks Ribasphere 200 mg tablets (800 mg per day: two 200 mg tablets in the morning and two 200 mg tablets in the evening) by mouth twice daily for 24 weeks Daclatasvir 30 mg, 60 mg, or 90 mg tablets (depending on concomitant HIV regimen) once daily for 12 weeks

Biological: Pegylated Interferon Lambda-1a; Drug: Daclatasvir (DCV); Drug: Ribasphere (RBV)

Cohort B: GT-1 or -4 HCV Treatment Naïve Subjects

EXPERIMENTAL

Pegylated Interferon Lambda 180 µg solution, injection subcutaneously once weekly for 24 or 48 weeks Ribasphere 200 mg tablets, (1000 mg per day: two 200 mg tablets in the morning and three 200 mg tablets in the evening for subjects weighing \<75 kg and 1200 mg per day: three 200 mg tablets in morning and three 200 mg tablets in evening for subjects weighing ≥75 kg) by mouth twice daily for 24 or 48 weeks Daclatasvir 30 mg, 60 mg, or 90 mg tablets (depending on concomitant HIV regimen) once daily for 12 weeks

Biological: Pegylated Interferon Lambda-1a; Drug: Daclatasvir (DCV); Drug: Ribasphere (RBV)

Interventions

Pegylated Interferon Lambda-1a BIOLOGICAL

Also known as: BMS-914143

Cohort A: GT-2 or -3 HCV Treatment Naïve Subjects; Cohort B: GT-1 or -4 HCV Treatment Naïve Subjects

Daclatasvir (DCV) DRUG

Also known as: BMS-790052

Cohort A: GT-2 or -3 HCV Treatment Naïve Subjects; Cohort B: GT-1 or -4 HCV Treatment Naïve Subjects

Ribasphere (RBV) DRUG

Cohort A: GT-2 or -3 HCV Treatment Naïve Subjects; Cohort B: GT-1 or -4 HCV Treatment Naïve Subjects

Eligibility Criteria

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

You may qualify if:

• HCV Genotype-1, -2, -3 or -4 treatment naïve;
• HCV RNA ≥10,000 IU/mL at screening;
• HIV-1 infection \[(approximately 200 subjects receiving HAART, approximately 100 subjects not receiving highly active antiretroviral therapy (HAART)\];
• For subjects receiving HAART, HIV RNA must be below \<40 copies/mL at screening and \<200 copies/mL for at least 8 weeks prior to screening;
• CD4 cell count at screening must be ≥100 cells/μL if receiving HAART or ≥350 cells/μL if not receiving HAART)
• Seronegative for Hepatitis B Surface Antigen (HBsAg)
• Body Mass Index (BMI) of 18 to 35 kg/m2, inclusive. BMI=weight (kg)/\[height (m)\]2 at screening;
• Subjects with compensated cirrhosis are permitted, but the number of subjects will be capped at approximately 30%. If a subject does not have cirrhosis, a liver biopsy within 3 years prior to enrollment is required to demonstrate the absence of cirrhosis. If cirrhosis is present, any prior liver biopsy is sufficient. Fibroscan® or FibroTest are acceptable if performed within 1 year prior to treatment in countries where liver biopsy is not required prior to treatment and where non-invasive imaging tests are approved for staging of liver disease
• Subjects with mild to moderate hemophilia as defined as:
• Mild-factor level activity of 6-4% OR
• Moderate defined as factor level activity of 1-5%

You may not qualify if:

• Any evidence of liver disease other than chronic HCV;
• Subjects infected with human immunodeficiency virus (HIV-2);
• Diagnosed or suspected hepatocellular carcinoma;
• Decompensated liver disease;
• Presence of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections within 12 weeks prior to study entry (AIDS-defining opportunistic infections as defined by the CDC, (CDC, JAMA 1993 Feb 10;269(6):729-30)
• Laboratory values: ANC \<1.5 x 109 cells/L (\<1.2 x 109 cells/L for Blacks), platelet count \<90 x 109 cells/L, hemoglobin \<11 g/dL for females, hemoglobin \<12 g/dL for males;
• Subjects (receiving HAART) who had first initiated anti-retroviral therapy within last 8 weeks prior to Day 1; however, if changes are required to a subject's HAART regimen to meet the requirements of the protocol, these changes are allowed at the screening visit. Subjects should wait a minimum of 1 month prior to Day 1 after a repeat of HIV viral load has been confirmed, \<40 copies/mL
• Subjects on Zidovudine (AZT), Didanosine (ddI), or Stavudine (d4T);
• Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements
• Subjects with severe hemophilia (defined as \<1% factor activity level)

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (63)

Inland Empire Liver Foundation

Rialto, California, 92377, United States

Location

University Of California San Francisco

San Francisco, California, 94110, United States

Location

Kaiser Permanente Medical Center

San Francisco, California, 94118, United States

Location

University Of Colorado Denver & Hospital

Aurora, Colorado, 80045, United States

Location

University Of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Yale University

New Haven, Connecticut, 06510, United States

Location

Orlando Va Medical Center

Orlando, Florida, 32803, United States

Location

Emory Hospital Midtown Infectious Disease Clinic

Atlanta, Georgia, 30308, United States

Location

Emory University

Atlanta, Georgia, 30308, United States

Location

Mercy Medical Center

Baltimore, Maryland, 21202, United States

Location

Duke Clinical Research Institute

Durham, North Carolina, 27710, United States

Location

Lehigh Valley Health Network

Allentown, Pennsylvania, 18102, United States

Location

Ut Southwestern Medical Center

Dallas, Texas, 75235, United States

Location

Local Institution

Buenos Aires, Bs As, Buenos Aires, 1141, Argentina

Location

Local Institution

Mar del Plata, Buenos Aires, 7600, Argentina

Location

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Quilmes, Buenos Aires, 1878, Argentina

Location

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Buenos Aires, 1119, Argentina

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Buenos Aires, 1202, Argentina

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Antwerp, 2000, Belgium

Location

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Brussels, 1000, Belgium

Location

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Brussels, 1200, Belgium

Location

University Of Alberta Hospitals

Edmonton, Alberta, T6G 2B7, Canada

Location

St Pauls Hospital

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

Vancouver Id Reserach & Care Centre Society

Vancouver, British Columbia, V6Z 2C7, Canada

Location

Hamilton Health Sciences, Mcmaster Site

Hamilton, Ontario, L8V 1C3, Canada

Location

Ottawa Hospital General Campus

Ottawa, Ontario, K1H 8L6, Canada

Location

Ottawa Hospital

Ottawa, Ontario, K1H 8L6, Canada

Location

Mcgill University Health Centre (Muhc) Montreal Chest Institute

Montreal, Quebec, H2X 2P4, Canada

Location

Local Institution

Le Kremlin-Bicêtre, 94275, France

Location

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Lyon, 69317, France

Location

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Paris, 75010, France

Location

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Paris, 75020, France

Location

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Pessac, 33604, France

Location

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Berlin, 13353, Germany

Location

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Bonn, 53105, Germany

Location

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Bonn, 53127, Germany

Location

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Hamburg, 20146, Germany

Location

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Antella (fi), 50011, Italy

Location

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Brescia, 25123, Italy

Location

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Milan, 20127, Italy

Location

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Monza, 20052, Italy

Location

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Roma, 00149, Italy

Location

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Ciudad Juárez, Chihuahua, 35350, Mexico

Location

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León, Guanajuato, 37320, Mexico

Location

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Guadalajara, Jalisco, 44280, Mexico

Location

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Mexico City, Mexico City, 14080, Mexico

Location

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Lodz, 91-347, Poland

Location

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Wroclaw, 50-220, Poland

Location

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Moscow, 105275, Russia

Location

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Moscow, 111123, Russia

Location

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Saint Petersburg, 190103, Russia

Location

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Saint Petersburg, 196645, Russia

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Volgograd, 400040, Russia

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Barcelona, 08029, Spain

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Cartagena (Murcia), 30202, Spain

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Donosti-San Sebastian, 20014, Spain

Location

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Madrid, 28034, Spain

Location

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Madrid, 28041, Spain

Location

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London, Greater London, SW10 9TH, United Kingdom

Location

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Brighton, BN2 5BE, United Kingdom

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London, E11BB, United Kingdom

Location

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London, NW3 2QG, United Kingdom

Location

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London, W2 1NY, United Kingdom

Location

Related Publications (1)

• Nelson M, Rubio R, Lazzarin A, Romanova S, Luetkemeyer A, Conway B, Molina JM, Xu D, Srinivasan S, Portsmouth S. Safety and Efficacy of Pegylated Interferon Lambda, Ribavirin, and Daclatasvir in HCV and HIV-Coinfected Patients. J Interferon Cytokine Res. 2017 Mar;37(3):103-111. doi: 10.1089/jir.2016.0082. Epub 2017 Feb 17.

  PMID: 28282271 DERIVED

Related Links

• BMS clinical trial educational resource
• Investigator Inquiry form
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Interventions

peginterferon lambda-1a; daclatasvir; Ribavirin

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Limitations and Caveats

The study was ended prematurely, giving few participants an opportunity to reach follow-up week 24

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

clinical.trials@bms.com

Please email

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2013
• First Posted: June 3, 2013
• Study Start: July 11, 2013
• Primary Completion: August 27, 2015
• Study Completion: August 27, 2015
• Last Updated: June 13, 2023
• Results First Posted: June 13, 2023

Record last verified: 2023-02

Locations

PL (2); RU (5); AR (5); ME (4); DE (4); US (13); BE (3); CA (7); FR (5); GB (5); ES (5); IT (5)