A Phase IIIb Study of the Safety, Efficacy, and Tolerability of Switching to a Fixed-dose Combination of Abacavir/Dolutegravir/ Lamivudine From Current Antiretroviral Regimen

NCT02105987 | Completed Phase 3 Results

• 1 other identifier: 201147
• Study Type: interventional
• Target: 555
• Locations: 3 countries
• Sites: 103

Brief Summary

This study is a 48-week, Phase IIIb, randomly assigned, open-label, active-controlled, multicenter, parallel group, non-inferiority study. This study is designed to demonstrate the non-inferior antiviral activity of switching to the Abacavir (ABC) 600 milligrams (mg)/Dolutegravir(DTG) 50 mg/Lamivudine (3TC) 300 mg fixed-dose combination (FDC) compared with continuing the subject's current suppressive regimen through 24 weeks. The study will be conducted in approximately 538 Human Immunodeficiency Virus -1 (HIV-1) infected individuals who are on stable suppressive combination antiretroviral therapy (cART) with 2 Nucleoside reverse transcriptase inhibitors (NRTIs) plus either a protease inhibitor (PI), an non-nucleoside reverse transcriptase inhibitor (NNRTI), or an integrase inhibitor (INI). Eligible subjects will be randomly assigned 1:1 to continue their current regimen (approximately 269 subjects) or be switched to ABC/DTG/3TC FDC (approximately 269 subjects) once daily for 24 weeks. At Week 24, individuals originally randomly assigned to continue their current regimen will switch to ABC/DTG/3TC FDC and be followed for an additional 24 weeks. Individuals initially randomly assigned to ABC/DTG/3TC FDC will continue on that treatment arm for an additional 24 weeks. A pharmacokinetic (PK) substudy will be conducted at a small number of sites (approximately 10) to evaluate predose DTG concentrations as well as residual drug concentrations of efavirenz (EFV), nevaripine (NVP), amprenavir (APV) and tipranavir (TPV) in a subgroup of subjects who switch from EFV, NVP, fosamprenavir/ritonavir (FPV/r) or tipranavir/ritonavir (TPV/r).

Conditions

Infection, Human Immunodeficiency Virus

Keywords

Abacavir/dolutegravir/lamivudine; Fixed-dose combination; Once daily; Trii; Single-tablet regimen

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) <50 Copies Per Milliliter (c/mL) at Week 24 Using the Snapshot Algorithm

  The Food and Drug Administration (FDA) snapshot (Missing, Switch or Discontinuation = Failure) algorithm is intended to be primarily a virologic assessment of the endpoint, and as such follows a "virology first" hierarchy. Virologic Success (e.g., \<50 c/mL) or virologic failure within an analysis window is typically determined by the last available HIV-1 RNA measurement in that window and in the treatment phase of interest (e.g., Week 24 snapshot outcomes of the early switch phase will not use HIV-1 RNA data from the late switch phase, even if such data is within the Week 24 analysis window). A virologic failure occurs when a participant changes to their ART regimen (e.g., addition of other ARTs to the study-specified regimens, or switches in components of the current ART regimen).

  Week 24

Secondary Outcomes (23)

• Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at Week 24

  Baseline and Week 24

• Number of Participants in the Virologic Non-response Category From the Snapshot Analysis at Week 24

  Week 24

• Number of Participants With Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) up to 24 Weeks

  Baseline and up to 24 weeks

• Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to 24 Weeks

  Baseline and up to 24 weeks

• Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities up to 24 Weeks

  Baseline and up to 24 weeks

Study Arms (2)

ABC/DTG/3TC

EXPERIMENTAL

Subject will take ABC 600 mg/DTG 50 mg/3TC 300 mg FDC once daily in the morning or the evening, at approximately the same time each day for 24 weeks. After Week 24, subjects will continue on this treatment arm for an additional 24 weeks.

Drug: ABC/DTG/3TC FDC

Comparator

ACTIVE COMPARATOR

Subjects will continue on their current Combination antiretroviral therapy (cART) regimen for 24 weeks. At Week 24, subjects will switch to ABC/DTG/3TC FDC for an additional 24 weeks.

Drug: Ongoing cART regimen

Interventions

ABC/DTG/3TC FDC DRUG

Purple, oval, biconvex tablets containing 702 mg Abacavir sulphate which is equivalent to 600 mg ABC, 52.62 mg Dolutegravir sodium which is equivalent to 50 mg Dolutegravir free acid and 300 mg 3TC

ABC/DTG/3TC

Ongoing cART regimen DRUG

Stable cART regimens including boosted PI (or ATV unboosted) + 2 NRTIs; NNRTI + 2 NRTIs, or INI (RAL or EVG)+ 2 NRTIs

Comparator

Eligibility Criteria

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

You may qualify if:

• Be able to understand and comply with protocol requirements, instructions, and restrictions;
• Be likely to complete the study as planned;
• Be considered appropriate candidates for participation in an investigative clinical trial with oral medication (e.g., no active substance abuse, acute major organ disease, or planned long-term work assignments out of the country, etc.).
• Signed and dated written informed consent is obtained from the subject or the subject's legal representative prior to screening
• HIV-1 infected men or women \>=18 years of age;
• A female may be eligible to enter and participate in the study if she: a. Is of non-childbearing potential either defined as post-menopausal (12 months of spontaneous amenorrhea and \>=45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy, or bilateral oophorectomy or,
• A female may be eligible to enter and participate in the study if she: b. Is of childbearing potential with a negative pregnancy test at both Screening and Day 1 and agrees to use one of the following methods of contraception to avoid pregnancy: Complete abstinence from intercourse from 2 weeks prior to administration of study drug, throughout the study, and for at least 2 weeks after discontinuation of all study drugs; Double barrier method (e.g., male condom/spermicide, male condom/diaphragm, diaphragm/spermicide); Any intrauterine device (IUD) with published data showing that the expected failure rate is \<1% per year ; Male partner sterilization prior to the female subject's entry into the study and this male is the sole partner for that subject; Approved hormonal contraception for subjects randomly assigned to the ABC/DTG/3TC arm or approved hormonal contraception plus a barrier method for subjects assigned to continued antiretroviral therapy arm; Any other method with published data showing that the expected failure rate is \<1% per year.
• Any contraception method must be used consistently, in accordance with the approved product label and for at least 2 weeks after discontinuation of study drug. A childbearing potential female subject who starts the study using complete abstinence as her contraceptive method and decides to become sexually active must use the double barrier method either as a bridge to an approved hormonal contraception (if possible) or as a method of choice to be maintained from that moment onwards.
• All subjects participating in the study should be counselled on safer sexual practices including the use of effective barrier methods (e.g., male condom/spermicide).
• Within the last year, 2 consecutive plasma HIV-1 Ribonucleic acid (RNA) measurements \<50 copies/millilitres (c/mL) and plasma HIV-1 RNA\<50 c/mL at Screening (\<75 b Deoxyribonucleic acid \[bDNA\] is considered equal to \<50 c/mL); Subjects who present at initial screening with a viral load between 50 to 200 c/mL can be retested once within the screening period.
• Must be on current regimen (whether first or second line Combination antiretroviral therapy \[cART\]) for at least 6 months prior to Screening;
• Acceptable stable cART regimens prior to Screening include: • Boosted PI (or Atazanavir \[ATV\]) unboosted) + 2 NRTIs, NNRTI + 2 NRTIs, • INI + 2 NRTIs. For subjects on an INI, their INI at Screening must be RAL or Elvitegravir (EVG)
• Any switch to a second line regimen, defined as change of a single drug or multiple drugs simultaneously, must have occurred due to tolerability and/or safety concerns.
• Subject must have achieved plasma HIV-1 RNA level \<50 c/mL within 6 months of start of initial cART regimen with no plasma HIV-1 RNA level \>200 c/mL following initial suppression;
• Documentation that the subject is negative for the human leukocyte antigen (HLA) B\*5701 allele;

You may not qualify if:

• Women who are breastfeeding;
• Any evidence of an active (Centers for Disease Control and Prevention \[CDC\] Category C) disease. Exceptions include cutaneous Kaposi's sarcoma not requiring systemic therapy and historic CD4+ cell counts of \<200 cells/cubic millimeter (mm).
• Subjects with any degree of hepatic impairment;
• Subjects positive for hepatitis B virus surface antigen (+HBsAg) at Screening or with an anticipated need for hepatitis C virus (HCV) therapy during the study;
• History or presence of allergy to the study drugs or their components or drugs of their class;
• Subjects who, in the investigator's judgment, pose a significant suicidality risk. Recent history of suicidal behavior and/or suicidal ideation may be considered as evidence of serious suicide risk;
• Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening;
• Treatment with any of the following agents within 28 days of Screening: radiation therapy, cytotoxic chemotherapeutic agents, any immunomodulators that alter immune responses;
• Exposure to an experimental drug or experimental vaccine within either 28 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to the first dose of study drug;
• A history of use of only mono or dual NRTI therapy prior to starting cART;
• Use of etravirine at time of switch;
• Use of DTG at time of switch;
• Subjects receiving any prohibited medication listed in the protocol and who are unwilling or unable to switch to an alternate medication
• Evidence of primary viral resistance based on the presence of any resistance-associated major PI or any NRTI, NNRTI, or INI mutation in any prior resistance genotype assay result;
• Any verified Grade 4 laboratory abnormality, with the exception of Grade 4 triglyceride abnormalities. A single repeat test is allowed during the screening period to verify a result;

Sponsors & Collaborators

• ViiV Healthcare: lead
• PPD Development, LP: collaborator
• GlaxoSmithKline: collaborator

Study Sites (103)

GSK Investigational Site

Phoenix, Arizona, 85012, United States

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GSK Investigational Site

Phoenix, Arizona, 85015, United States

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GSK Investigational Site

Bakersfield, California, 93301, United States

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GSK Investigational Site

Beverly Hills, California, 90211, United States

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GSK Investigational Site

Long Beach, California, 90813, United States

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GSK Investigational Site

Los Angeles, California, 90028, United States

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GSK Investigational Site

Los Angeles, California, 90033, United States

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GSK Investigational Site

Los Angeles, California, 90035, United States

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GSK Investigational Site

Los Angeles, California, 90036, United States

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GSK Investigational Site

Los Angeles, California, 90069, United States

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GSK Investigational Site

Newport Beach, California, 92663, United States

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GSK Investigational Site

Oakland, California, 94602, United States

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GSK Investigational Site

Sacramento, California, 95825, United States

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GSK Investigational Site

San Diego, California, 92103, United States

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GSK Investigational Site

San Francisco, California, 94109, United States

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GSK Investigational Site

San Francisco, California, 94115, United States

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GSK Investigational Site

San Francisco, California, 94118, United States

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GSK Investigational Site

San Leandro, California, 94577, United States

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GSK Investigational Site

Torrance, California, 90502, United States

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GSK Investigational Site

Denver, Colorado, 80205-5422, United States

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GSK Investigational Site

Denver, Colorado, 80209, United States

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GSK Investigational Site

Norwalk, Connecticut, 06850, United States

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GSK Investigational Site

Washington D.C., District of Columbia, 20007, United States

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GSK Investigational Site

Washington D.C., District of Columbia, 20009, United States

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GSK Investigational Site

Washington D.C., District of Columbia, 20036, United States

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GSK Investigational Site

Washington D.C., District of Columbia, 20037, United States

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GSK Investigational Site

Fort Lauderdale, Florida, 33316, United States

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GSK Investigational Site

Ft. Pierce, Florida, 34982, United States

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GSK Investigational Site

Jacksonville, Florida, 32209, United States

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GSK Investigational Site

Miami, Florida, 33133, United States

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GSK Investigational Site

Miami, Florida, 33136, United States

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GSK Investigational Site

Orlando, Florida, 32803, United States

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GSK Investigational Site

Pensacola, Florida, 32504, United States

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GSK Investigational Site

Tampa, Florida, 33614, United States

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GSK Investigational Site

Vero Beach, Florida, 32960-6571, United States

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GSK Investigational Site

West Palm Beach, Florida, 33401, United States

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GSK Investigational Site

Atlanta, Georgia, 30308, United States

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GSK Investigational Site

Atlanta, Georgia, 30312, United States

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GSK Investigational Site

Atlanta, Georgia, 30339, United States

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GSK Investigational Site

Augusta, Georgia, 30912-3130, United States

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GSK Investigational Site

Decatur, Georgia, 30033, United States

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GSK Investigational Site

Savannah, Georgia, 31405, United States

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GSK Investigational Site

Honolulu, Hawaii, 96813, United States

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GSK Investigational Site

Chicago, Illinois, 60612-3833, United States

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GSK Investigational Site

Chicago, Illinois, 60612, United States

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GSK Investigational Site

Indianapolis, Indiana, 46202, United States

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GSK Investigational Site

Iowa City, Iowa, 52242, United States

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GSK Investigational Site

New Orleans, Louisiana, 70121, United States

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GSK Investigational Site

Springfield, Massachusetts, 01105, United States

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GSK Investigational Site

Ann Arbor, Michigan, 48109, United States

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GSK Investigational Site

Berkley, Michigan, 48072, United States

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GSK Investigational Site

Minneapolis, Minnesota, 55407, United States

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GSK Investigational Site

Minneapolis, Minnesota, 55415, United States

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GSK Investigational Site

Kansas City, Missouri, 64111, United States

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GSK Investigational Site

St Louis, Missouri, 63108, United States

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GSK Investigational Site

St Louis, Missouri, 63110, United States

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GSK Investigational Site

St Louis, Missouri, 63139, United States

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GSK Investigational Site

Las Vegas, Nevada, 89031, United States

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GSK Investigational Site

Camden, New Jersey, 08103, United States

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GSK Investigational Site

Hillsborough, New Jersey, 08844, United States

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GSK Investigational Site

Newark, New Jersey, 07102, United States

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GSK Investigational Site

Santa Fe, New Mexico, 87505, United States

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GSK Investigational Site

Buffalo, New York, 14215, United States

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GSK Investigational Site

Manhasset, New York, 11030, United States

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GSK Investigational Site

New York, New York, 10001, United States

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GSK Investigational Site

The Bronx, New York, 10467, United States

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GSK Investigational Site

Valhalla, New York, 10595, United States

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GSK Investigational Site

Charlotte, North Carolina, 28207, United States

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GSK Investigational Site

Greensboro, North Carolina, 27401, United States

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GSK Investigational Site

Akron, Ohio, 44304, United States

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GSK Investigational Site

Cincinnati, Ohio, 45267-0405, United States

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GSK Investigational Site

Tulsa, Oklahoma, 74127, United States

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GSK Investigational Site

Allentown, Pennsylvania, 18102, United States

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GSK Investigational Site

Philadelphia, Pennsylvania, 19107, United States

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GSK Investigational Site

Pittsburgh, Pennsylvania, 15212, United States

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GSK Investigational Site

Charleston, South Carolina, 29425, United States

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GSK Investigational Site

Austin, Texas, 78705, United States

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GSK Investigational Site

Bellaire, Texas, 77401, United States

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GSK Investigational Site

Dallas, Texas, 75208, United States

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GSK Investigational Site

Dallas, Texas, 75246, United States

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GSK Investigational Site

Dallas, Texas, 75390-9113, United States

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GSK Investigational Site

Fort Worth, Texas, 76104, United States

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GSK Investigational Site

Houston, Texas, 77098, United States

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GSK Investigational Site

Longview, Texas, 75605, United States

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GSK Investigational Site

Annandale, Virginia, 22003, United States

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GSK Investigational Site

Lynchburg, Virginia, 24501, United States

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GSK Investigational Site

Seattle, Washington, 98104, United States

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GSK Investigational Site

Calgary, Alberta, T2R 0X7, Canada

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GSK Investigational Site

Vancouver, British Columbia, V6Z 2C7, Canada

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GSK Investigational Site

Vancouver, British Columbia, V6Z 2T1, Canada

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GSK Investigational Site

Victoria, British Columbia, V8W 1M8, Canada

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GSK Investigational Site

Winnipeg, Manitoba, R3A 1R9, Canada

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GSK Investigational Site

Toronto, Ontario, M4N 3M5, Canada

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GSK Investigational Site

Toronto, Ontario, M4T 3A7, Canada

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GSK Investigational Site

Toronto, Ontario, M5G 1K2, Canada

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GSK Investigational Site

Toronto, Ontario, M5G 2N2, Canada

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GSK Investigational Site

Montreal, Quebec, H2L 4P9, Canada

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GSK Investigational Site

Montreal, Quebec, H2L 5B1, Canada

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GSK Investigational Site

Montreal, Quebec, H3A 1T1, Canada

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GSK Investigational Site

Ponce, Puerto Rico, 00717-1567, Puerto Rico

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GSK Investigational Site

Rio Piedras, Puerto Rico, 00935, Puerto Rico

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GSK Investigational Site

San Juan, Puerto Rico, 00936-8344, Puerto Rico

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GSK Investigational Site

San Juan, 00909, Puerto Rico

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Related Publications (1)

• Trottier B, Lake JE, Logue K, Brinson C, Santiago L, Brennan C, Koteff JA, Wynne B, Hopking J, Granier C, Aboud M. Dolutegravir/abacavir/lamivudine versus current ART in virally suppressed patients (STRIIVING): a 48-week, randomized, non-inferiority, open-label, Phase IIIb study. Antivir Ther. 2017;22(4):295-305. doi: 10.3851/IMP3166. Epub 2017 Apr 12.

  PMID: 28401876 DERIVED

MeSH Terms

Conditions

Infections; Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  ViiV Healthcare

  STUDY DIRECTOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: April 3, 2014
• First Posted: April 7, 2014
• Study Start: April 1, 2014
• Primary Completion: April 1, 2015
• Study Completion: December 1, 2015
• Last Updated: January 4, 2017
• Results First Posted: February 25, 2016

Record last verified: 2016-11

Locations

US (87); CA (12); PR (4)