Dolutegravir Plus Lamivudine Dual Therapy in Treatment Naïve HIV-1 Patients

NCT02582684 | Completed Phase 2 Results DMC

• 2 other identifiers: ACTG A53532UM1AI068636
• Study Type: interventional
• Target: 122
• Locations: 2 countries
• Sites: 26

Brief Summary

This study was done to see if the combination of two anti-HIV medicines, dolutegravir (DTG, Tivicay) and lamivudine (3TC, Epivir) taken once a day, provide a safe, effective, and well-tolerated treatment for HIV. DTG is a type of HIV medicine called an integrase inhibitor; 3TC is a type of HIV medicine called a reverse transcriptase inhibitor. DTG works by blocking integrase and 3TC works by blocking reverse transcriptase, two HIV proteins (enzymes). This prevents HIV from multiplying and lowers the viral load (amount of HIV in the blood). Both DTG and 3TC are currently part of Food and Drug Administration (FDA) recommended regimens along with a third active drug. Since some HIV medicines have side effects and are costly, there is interest in whether HIV can be successfully controlled with fewer than three HIV drugs.

Conditions

HIV-1 Infection

Outcome Measures

Primary Outcomes (1)

• Virologic Status at Week 24

  Numbers of Participants With Virologic Success, Virologic Non-Success, and no Virologic Data at Week 24 Window are provided below. Virologic success is defined as HIV-1 RNA \<50 copies/mL and on study treatment (FDA Snapshot definition).

  At 24 weeks after study entry

Secondary Outcomes (15)

• Virologic Status at Week 12

  At 12 weeks after study entry

• Virologic Status at Week 48

  At 48 weeks after study entry

• Virologic Failure

  Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40 and 48

• Proportion of Participants With Plasma HIV-1 RNA < 50 Copies/mL - Missing = Failure

  Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40 and 48

• Proportion of Participants With Plasma HIV-1 RNA < 200 Copies/mL - Missing = Failure

  Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40 and 48

Study Arms (1)

Arm 1: DTG 50 mg + 3TC 300 mg

EXPERIMENTAL

Dolutegravir 50mg and Lamivudine 300mg, orally daily

Drug: Dolutegravir; Drug: Lamivudine

Interventions

Dolutegravir DRUG

Participants were prescribed 50 mg of DTG orally daily

Also known as: DTG

Arm 1: DTG 50 mg + 3TC 300 mg

Lamivudine DRUG

Participants were prescribed 300 mg of 3TC orally daily.

Also known as: 3TC

Arm 1: DTG 50 mg + 3TC 300 mg

Eligibility Criteria

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

You may qualify if:

• HIV-1 infection.
• Plasma HIV-1 RNA ≥1000 copies/mL and \<500,000 copies/mL obtained within 90 days prior to study entry.
• No evidence of any RT, any integrase, or major protease resistance mutation (according to the 2014 IAS-USA drug resistance mutations list, available at https://www.iasusa.org/sites/default/files/tam/22-3-642.pdf) based on pre-ARV (antiretroviral) treatment genotype performed any time prior to study entry.
• ARV treatment drug-naive (defined as no previous ARV treatment at any time prior to study entry, with the exception of successful post-exposure prophylaxis (PEP) or pre-exposure prophylaxis (PrEP).
• The following laboratory values obtained within 45 days prior to study entry:
• ANC (absolute neutrophil count) ≥750/mm\^3
• Hemoglobin ≥10.0 g/dL
• Platelets ≥ 50,000/mm\^3
• Calculated creatinine clearance (CrCl) ≥50 mL/min, as estimated by the Cockcroft-Gault equation
• AST (aspartate aminotransferase) \<5 x ULN (upper limit of normal)
• ALT (alanine aminotransferase) \<5x ULN
• Total bilirubin \<1.5 x ULN
• Hepatitis B surface antigen negative within 45 days prior to study entry.
• For women with reproductive potential, negative serum or urine pregnancy test at screening and within 48 hours prior to study entry.
• If participating in sexual activity that could lead to pregnancy, female participants with reproductive potential must have agreed to use one form of contraceptive as listed in the protocol while receiving protocol-specified medications and for 30 days after stopping the medications.

You may not qualify if:

• Serious illness requiring systemic treatment and/or hospitalization.
• Treatment within 30 days prior to study entry with immune modulators such as systemic steroids, interleukins, interferons, granulocyte colony-stimulating factor (G-CSF), erythropoietin, or any investigational therapy.
• Pregnancy or breastfeeding.
• Receipt of systemic cytotoxic chemotherapy or dofetilide.
• Known allergy/sensitivity to any of the study drugs or their formulations.
• Active drug or alcohol use or dependence that may interfere with adherence to study requirements, in the opinion of the site investigator.
• Active hepatitis C virus (HCV) treatment or anticipated need for treatment within study period.
• Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• Severe hepatic impairment (Class C) as determined by Child-Pugh classification.

Sponsors & Collaborators

• Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (26)

University of Southern California CRS (1201)

Los Angeles, California, 90033, United States

Location

UCLA CARE Center CRS (601)

Los Angeles, California, 90095, United States

Location

Ucsd, Avrc Crs (701)

San Diego, California, 92103, United States

Location

Harbor-UCLA Med. Ctr. CRS (603)

Torrance, California, 90502, United States

Location

University of Colorado Hospital CRS (6101)

Aurora, Colorado, 80045, United States

Location

Univ. of Miami AIDS CRS (901)

Miami, Florida, 33136, United States

Location

The Ponce de Leon Center CRS (5802)

Atlanta, Georgia, 30308, United States

Location

Northwestern University CRS (2701)

Chicago, Illinois, 60611, United States

Location

Rush Univ. Med. Ctr. ACTG CRS (2702)

Chicago, Illinois, 60612, United States

Location

Massachusetts General Hospital ACTG CRS (101)

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hosp. ACTG CRS (107)

Boston, Massachusetts, 02115, United States

Location

Washington University CRS (2101)

St Louis, Missouri, 63110, United States

Location

Cornell CRS (7804)

New York, New York, 10011, United States

Location

Weill Med. College of Cornell Univ., The Cornell CTU -Chelsea (7803)

New York, New York, 10011, United States

Location

Columbia Physicians and Surgeons CRS (30329)

New York, New York, 10032, United States

Location

University of Rochester Adult HIV Therapeutic Strategies Network CRS (31787)

Rochester, New York, 14642, United States

Location

3201 Chapel Hill CRS

Chapel Hill, North Carolina, 27516, United States

Location

Greensboro CRS (3203)

Greensboro, North Carolina, 27401, United States

Location

Univ. of Cincinnati CRS (2401)

Cincinnati, Ohio, 45267, United States

Location

The Ohio State Univ. AIDS CRS (2301)

Columbus, Ohio, 43210, United States

Location

Hosp. of the Univ. of Pennsylvania CRS (6201)

Philadelphia, Pennsylvania, 19104, United States

Location

The Miriam Hospital ACTG CRS (2951)

Providence, Rhode Island, 02906, United States

Location

Vanderbilt Therapeutics CRS (3652)

Nashville, Tennessee, 37204, United States

Location

31443 Trinity Health and Wellness Center CRS

Dallas, Texas, 75208, United States

Location

Houston AIDS Research Team CRS (31473)

Houston, Texas, 77030, United States

Location

Puerto Rico-AIDS CRS (5401)

San Juan, 00935, Puerto Rico

Location

Related Publications (2)

• Nyaku AN, Zheng L, Gulick RM, Olefsky M, Berzins B, Wallis CL, Godfrey C, Sax PE, Acosta EP, Haas DW, Smith KY, Sha BE, Van Dam CN, Taiwo BO; ACTG A5353 Study Team. Dolutegravir plus lamivudine for initial treatment of HIV-1-infected participants with HIV-1 RNA <500 000 copies/mL: week 48 outcomes from ACTG 5353. J Antimicrob Chemother. 2019 May 1;74(5):1376-1380. doi: 10.1093/jac/dky564.

  PMID: 30668695 DERIVED

• Taiwo BO, Zheng L, Stefanescu A, Nyaku A, Bezins B, Wallis CL, Godfrey C, Sax PE, Acosta E, Haas D, Smith KY, Sha B, Van Dam C, Gulick RM. ACTG A5353: A Pilot Study of Dolutegravir Plus Lamivudine for Initial Treatment of Human Immunodeficiency Virus-1 (HIV-1)-infected Participants With HIV-1 RNA <500000 Copies/mL. Clin Infect Dis. 2018 May 17;66(11):1689-1697. doi: 10.1093/cid/cix1083.

  PMID: 29253097 DERIVED

Related Links

• DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0 November 2014
• FDA Snapshot Definition (refer to Appendix A in FDA Snapshot PDF)
• DAIDS Adverse Events Manual, Version 2.0 January 2010

MeSH Terms

Interventions

dolutegravir; Lamivudine

Intervention Hierarchy (Ancestors)

Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides

Results Point of Contact

• Title: ACTG Clinicaltrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social and Scientific Systems, Inc.

ACTGCT.Gov@s-3.com

(301) 628-3313

Study Officials

• Roy Gulick, MD, MPH

  Weill Medical College of Cornell University

  STUDY CHAIR

• Babafemi Taiwo, MBBS

  Northwestern University

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2015
• First Posted: October 21, 2015
• Study Start: December 8, 2015
• Primary Completion: February 28, 2017
• Study Completion: September 26, 2017
• Last Updated: May 9, 2018
• Results First Posted: March 30, 2018

Record last verified: 2018-04

Locations

PR (1); US (25)