A Phase II, Multicenter, Single-Arm, Open-Label Clinical Trial to Evaluate the Safety and Efficacy of Triple Therapy With Dolutegravir Plus 2 NRTIs, in Treatment-Naïve HIV-2 Infected Subjects
Overview
- Phase
- Phase 2
- Intervention
- Dolutegravir 50 mg
- Conditions
- HIV II Infection
- Sponsor
- Blueclinical, Ltd.
- Enrollment
- 30
- Locations
- 6
- Primary Endpoint
- Efficacy analysis- treatment efficacy, as measured by the "overall treatment success defined as proportion of patients with "global success" at week 48.
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
Multicenter, single-arm, open-label clinical trial to evaluate the efficacy, the safety and the tolerability of 50 mg dolutegravir once daily (q.d.) given in combination with 2 NRTIs backbone in HIV-2 positive, treatment-naïve subjects.
Detailed Description
Subjects who fulfill all inclusion criteria and none of the exclusion criteria, after giving informed consent, will be eligible for participation in this study. At the Visit 2 (Day1) subjects will receive the study medication and instructions for its administration. Thereafter, subjects will return to the investigational site at week 4, 12, 24, 36 and 48, for efficacy and safety assessments. Subjects who meet the virologic failure criteria will return to the investigational site approximately one week later to repeat viral RNA testing (Virologic Failure Confirmation visit). If virologic failure is confirmed and the viral load meets the criteria for resistance testing, viral resistance testing will then be performed.
Investigators
Eligibility Criteria
Inclusion Criteria
- •A subject is eligible for the study if he/she fulfills all of the following inclusion criteria:
- •Able to understand and willing to comply with all the requirements of the study, as confirmed by giving voluntary written informed consent for participation.
- •Male or female gender.
- •Age ≥ 18 years on the day of signing the informed consent.
- •HIV-2 positive as determined by a positive result in the respective assay.
- •CD4 count ≤500 cells/mm3 (in case of undetectable baseline HIV-2 viral load); and/or classified as B- or C-stage, by the HIV disease staging and classification system of Centers for Disease Control and Prevention (CDC); and/or have detectable viral load irrespective of CD4 count; and/or have other medical conditions / co-morbidities in which treatment is considered, according to European AIDS Clinical Society (EACS) and national guidelines;
- •Naïve to ART including investigational antiretroviral agents .
- •Considered clinically stable with no signs or symptoms of active infection, at the time of entry into the study (i.e., clinical status and all chronic medications should be unchanged for at least 2 weeks prior to the start of treatment in this study), in the opinion of the investigator.
- •If woman or man with reproductive potential, agrees to adopt one of the following effective contraceptive methods throughout the study:
- •True abstinence, if this is in line with the preferred and usual lifestyle of the subject \[Period abstinence (e.g., abstinence only on certain calendar days, abstinence only during ovulation period, use of symptothermal method, use of post-ovulation methods) and withdrawal are not acceptable methods of contraception\].
Exclusion Criteria
- •A subject is not eligible for the trial if he/she fulfills any of the following exclusion criteria:
- •History or presence of allergy to the study drugs or their components.
- •HIV-1 infection or HIV-1/HIV-2 dual infection.
- •History or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might confound the results of the study, or interfere with the subject's participation for the full duration of the study, such that it is not in the best interest of the subject to participate.
- •Documented or known resistance to DTG and/or NRTIs.
- •Treatment with systemic immunosuppressive therapy or immune modulators within 30 days prior to treatment in this study or is anticipated to need them during the course of the study.
- •NOTE: "Short courses" of corticosteroids (e.g., as for asthma exacerbation) will be allowed. "Short courses" mean a use of corticosteroids for less than 7 days.
- •Requiring or is anticipated to require any of the prohibited medications while in the study (dofetilide, inducers of CYP3A4, including phenobarbital, phenytoin, carbamazepine and rifampicin).
- •NOTE: Subjects must discontinue phenobarbital, phenytoin, carbamazepine, and rifampicin at least 14 days prior to the treatment phase of the study.
- •Current (active) diagnosis of tuberculosis.
Arms & Interventions
: Dolutegravir (DTG)
Intervention: Dolutegravir 50 mg
Outcomes
Primary Outcomes
Efficacy analysis- treatment efficacy, as measured by the "overall treatment success defined as proportion of patients with "global success" at week 48.
Time Frame: 48 Weeks
The primary objective of this study is to evaluate the efficacy of DTG in combination with two NRTIs \[ABC/3TC or TDF/FTC\] in the treatment of HIV-2 treatment-naïve subjects, as measured by the proportion of subjects achieving a plasma viral load of \<40 copies/mL and/or by the change from baseline in CD4 cell count and in CD4/CD8 ratio at Week 48. Global success" is a composite variable defined as a plasma HIV-2 RNA viral load \<40 copies/mL and a delta of CD4 depending on the initial CD4 count (CD4 delta \>+100 cells/mm3 for initial CD4s ≤ 500 cells/mm3; or CD4delta \> +50 cells/mm3 for initial CD4s \> 500 cells/mm3).
Secondary Outcomes
- Study treatment immunological effect(12, 24 and 48 Weeks)
- Safety and tolerability of the study treatment, as assessed by review of the accumulated safety data.(24 weeks or rebounder at least one week apart afte rinitial response)