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First-Line Treatment for HIV-2 (FIT-2)

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ClinicalTrials.gov Identifier: NCT02150993
Recruitment Status : Completed
First Posted : May 30, 2014
Last Update Posted : July 22, 2019
Sponsor:
Information provided by (Responsible Party):
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)

Tracking Information
First Submitted Date  ICMJE May 28, 2014
First Posted Date  ICMJE May 30, 2014
Last Update Posted Date July 22, 2019
Actual Study Start Date  ICMJE January 26, 2016
Actual Primary Completion Date May 15, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 20, 2017)
The "overall success" [ Time Frame: 96 weeks ]
The proportion of patients with "global success" at W96, defined by survival with a plasma HIV-2 RNA viral load of <50 copies/ml and the non-occurrence of AIDS classified events (excluding tuberculosis) and the non-occurrence of severe morbidities non-AIDS-defining illness (cardiovascular disease, kidney disease, severe bacterial disease) and a delta of CD4 depending on the initial CD4 count (CD4 delta> +100cells/mm3 for initial CD4s between 201 and 500 cells/mm3 or delta ≥0 cells/mm3 for initial CD4s > +500 cells/mm3) A treatment is considered to be effective if the "global success" is > 55 % at 96 weeks.
Original Primary Outcome Measures  ICMJE
 (submitted: May 29, 2014)
The "overall success" [ Time Frame: 96 weeks ]
The proportion of patients with "global success" at W96, defined by survival with a plasma HIV-2 RNA viral load of ≤50 copies/ml and the non-occurrence of AIDS classified events (excluding tuberculosis) and a delta of CD4 depending on the initial CD4 count (CD4 delta> +100cells/mm3 for initial CD4s between 201 and 500 cells/mm3 or delta> 50 cells/mm3 for initial CD4s > +500 cells/mm3) A treatment is considered to be effective if the "global success" is > 55 % at 96 weeks.
Change History Complete list of historical versions of study NCT02150993 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 13, 2018)
  • Therapeutic failure [ Time Frame: 24 weeks ]
    The percentage of patients in "treatment failure" defined by :
    1. death or
    2. a delta ≤0 CD4 cells / mm3 between W2 and W24 (or W48) for patients with baseline CD4 between 201 and 500 cells / mm3 or if % of decrease in CD4 > 20% between W2 and W24 (or W48) for patients with baseline CD4 > 500 cellules/mm3 or
    3. a plasma HIV-2 RNA viral load of > or =50 copies/ml or
    4. the occurrence of an AIDS defining event (excluding tuberculosis).
  • Therapeutic failure [ Time Frame: 48 weeks ]
    The percentage of patients in "treatment failure" defined by :
    1. death or
    2. a delta ≤0 CD4 cells / mm3 between W2 and W24 (or W48) for patients with baseline CD4 between 201 and 500 cells / mm3 or if % of decrease in CD4 > 20% between W0 and W24 (or W48) for patients with baseline CD4 > 500 cellules/mm3 or
    3. a plasma HIV-2 RNA viral load of > or = 50 copies/ml or
    4. the occurrence of an AIDS defining event (excluding tuberculosis).
  • Incidence and type of severe clinical or biological severe adverse events per arm [ Time Frame: between Week 0 and Week 96 ]
    Incidence and type of severe clinical or biological severe adverse event (grade 3 or 4)
  • The clinical progression [ Time Frame: between Week 0 and Week 96 ]
    The incidence of severe morbidity, defined as: AIDS morbidity, non-AIDS cancer, severe non-AIDS bacterial disease, or any disease leading to death
  • The evolution of CD4 counts [ Time Frame: between Week 0 and Week 96 ]
    Evolution of the absolute and percentage CD4 counts during follow-up
  • The evolution of plasma HIV-2 RNA load [ Time Frame: between at W0 and W96 ]
    Evolution of the plasma viral load during follow-up
  • The observance of antiretroviral treatment [ Time Frame: between W0 and W96 ]
    To describe the antiretroviral possession ratio and assessment of compliance by questionnaire
  • The resistance mutations profile [ Time Frame: Weeks 96 ]
    Description of new resistance mutations profiles in cases of treatment failure
  • The evolution of the HIV-2 DNA titers in PBMC [ Time Frame: between Week 0 and Week 96 ]
    To describe the evolution the HIV-2 DNA titers in PBMC
  • The frequency of treatment switches and discontinuations [ Time Frame: between Week 0 and Week 96 ]
    The frequency of modifications and discontinuations of treatment per arm
  • To model the long-term survival and cost-effectiveness ratio [ Time Frame: Weeks 96 ]
    The probability of survival and the incremental cost-effectiveness of these three treatment regimens
Original Secondary Outcome Measures  ICMJE
 (submitted: May 29, 2014)
  • Therapeutic failure [ Time Frame: 24 weeks ]
    The percentage of patients in "treatment failure" defined by :
    1. death or
    2. a delta CD4 ≤0 cells/mm3 or
    3. a plasma HIV-2 RNA viral load of >50 copies/ml or
    4. the occurrence of an AIDS defining event (excluding tuberculosis).
  • Therapeutic failure [ Time Frame: 48 weeks ]
    The percentage of patients in "treatment failure" defined by :
    1. death or
    2. a delta CD4 ≤0 cells/mm3 between or
    3. a plasma HIV-2 RNA viral load of >50 copies/ml or
    4. the occurrence of an AIDS defining event (excluding tuberculosis).
  • Incidence and type of severe clinical or biological severe adverse events (grade 3 or 4 on the ANRS grading table) per arm [ Time Frame: between Week 0 and Week 96 ]
  • The clinical progression [ Time Frame: between Week 0 and Week 96 ]
    The incidence of severe morbidity, defined as: AIDS morbidity, non-AIDS cancer, severe non-AIDS bacterial disease, or any disease leading to death
  • The evolution of CD4 counts [ Time Frame: between Week 0 and Week 96 ]
    Evolution of the absolute and percentage CD4 counts during follow-up
  • The evolution of plasma HIV-2 RNA load [ Time Frame: between at W0 and W96 ]
    Evolution of the plasma viral load during follow-up
  • The observance of antiretroviral treatment [ Time Frame: between W0 and W96 ]
    To describe the antiretroviral possession ratio and assessment of compliance by questionnaire
  • The resistance mutations profile [ Time Frame: Weeks 96 ]
    Description of new resistance mutations profiles in cases of treatment failure
  • The evolution of the HIV-2 DNA titers in PBMC [ Time Frame: between Week 0 and Week 96 ]
    To describe the evolution the HIV-2 DNA titers in PBMC
  • The frequency of treatment switches and discontinuations [ Time Frame: between Week 0 and Week 96 ]
    The frequency of modifications and discontinuations of treatment per arm
  • To model the long-term survival and cost-effectiveness ratio [ Time Frame: Weeks 96 ]
    The probability of survival and the incremental cost-effectiveness of these three treatment regimens
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE First-Line Treatment for HIV-2
Official Title  ICMJE A Randomized, Non-comparative, Phase IIb, Unblinded Trial, Evaluating the Efficacy and Safety of Tenofovir-emtricitabine or Lamivudine Plus Zidovudine, Lopinavir/Ritonavir, or Raltegravir, Among ARV-naïve HIV-2 Infected Adult Patients, in West Africa
Brief Summary

FIT-2 is a multi-country, phase IIb, randomized, non-comparative study, carried out in West Africa (Côte d'Ivoire, Burkina Faso, Senegal, Togo).

ARV-naïve HIV-2 infected adult patients will be recruited and followed during 96 weeks.

The objective is to evaluate the efficacy and safety of 3 first-line treatments in HIV-2 infected adult patients, in West Africa. A treatment will be considered as effective if more than 55% of patients in that arm attain "global success" at 96 weeks.

Detailed Description

Main objective

To determine in treatment-naïve HIV-2 infected patients, with CD4 counts above 200 cells/mm3, which of the following three regimens of first line treatment, Tenofovir (TDF), Emtricitabine or lamivudine (FTC or 3TC) plus Zidovudine (ZDV); TDF-FTC (3TC) plus Lopinavir/ritonavir (LPV / r); or TDF-FTC (3TC) plus raltegravir (RAL), will result in an "global success" rate of > 55% at week 96.

Number of participants : 210

Main outcome :

The proportion of patients with "global success" at W96, defined by survival with a plasma HIV-2 RNA viral load of <50 copies/ml and the non-occurrence of AIDS classified events (excluding tuberculosis) and the non-occurrence of severe morbidities non-AIDS-defining illness (cardiovascular disease, kidney disease, severe bacterial disease) and a delta of CD4 depending on the initial CD4 count (CD4 delta > +100cells/mm3 for initial CD4s between 201 and 500 cells/mm3 or delta ≥0 cells/mm3 for initial CD4s > +500 cells/mm3)

Inclusion criteria:

  • Infection by HIV-2 only;
  • Age > or = 18 years;
  • Naïve for antiretroviral therapy (including antiretroviral treatment in the context of PMTCT except taking a dose of Nevirapine for PMTCT)
  • CD4 >200 cells/mm3
  • Resident of the city where the study is held or of city suburbs to facilitate participation
  • Signed informed consent document
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HIV-2 Infection
Intervention  ICMJE
  • Drug: Tenofovir + Emtricitabine or Lamivudine + Zidovudine
    TDF +FTC or 3TC (Tenofovir disoproxil fumarate 245 mg and emtricitabine 200 mg or lamivudine 300mg) QD (evenings orally with meals) + ZDV (Zidovudine 300 mg) 1 tb BID (mornings and evenings orally)
    Other Names:
    • TDF+FTC (or 3TC) + ZDV
    • TDF+FTC (or 3TC) + AZT
  • Drug: Tenofovir + Emtricitabine or Lamivudine + Lopinavir/ritonavir
    TDF +FTC or 3TC (Tenofovir disoproxil fumarate 245 mg and emtricitabine 200 mg or lamivudine 300mg) QD (evenings orally with meals) + Lop/r (Lopinavir/ritonavir lopinavir 200/50 mg) 2 tbs BID (mornings and evenings orally)
    Other Name: TDF +FTC (or 3TC) +LPV/r
  • Drug: Tenofovir + Emtricitabine or Lamivudine + Raltegravir
    TDF +FTC or 3TC (Tenofovir disoproxil fumarate 245 mg and emtricitabine 200 mg or lamivudine 300mg) QD (evenings orally with meals) + RAL (Raltegravir 400 mg) 1 tb BID (mornings and evenings orally)
    Other Name: TDF +FTC (or 3TC) + RAL
Study Arms  ICMJE
  • Experimental: Arm A : TDF + FTC (or 3TC) + ZDV
    Tenofovir + Emtricitabine or Lamivudine + Zidovudine
    Intervention: Drug: Tenofovir + Emtricitabine or Lamivudine + Zidovudine
  • Experimental: TDF+FTC (or 3TC) +LPV/r
    Tenofovir + Emtricitabine or Lamivudine + Lopinavir/ritonavir
    Intervention: Drug: Tenofovir + Emtricitabine or Lamivudine + Lopinavir/ritonavir
  • Experimental: Arm C : TDF +FTC (or 3TC) + RAL
    Tenofovir + Emtricitabine or Lamivudine + Raltegravir
    Intervention: Drug: Tenofovir + Emtricitabine or Lamivudine + Raltegravir
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 29, 2014)
210
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE May 15, 2019
Actual Primary Completion Date May 15, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Infection by HIV-2 only;
  • Age > ou = 18 years;
  • Naïve for antiretroviral therapy (including antiretroviral treatment in the context of PMTCT except taking a dose of Nevirapine for PMTCT)
  • CD4 >200 cells/mm3
  • Resident of the city where the study is held or of city suburbs to facilitate participation
  • Signed informed consent document

Exclusion Criteria:

  • Current participation in any other clinical trial
  • Presence of opportunistic non-stabilized infections, of any serious or progressive disease, or of any clinical signs consistent with severe disease whose diagnosis is not yet confirmed, such as fever, weight loss, diarrhea or cough not yet explained (non-exhaustive list).
  • All pathology that leads in daily life to prefer one or the other of the three therapeutic regimens for medical reasons or to change the dosages specified in the test. This includes (but not limited to):
  • Hemoglobin ≤ 8 g / dL
  • Neutrophil count <500 cells/mm3
  • Renal impairment with creatinine clearance <50mL/mn
  • Blood platelet <50 000 cells/mm3
  • Decompensated heart failure
  • Hepatic failure Severe (TP<50% or cytolysis severe (ALAT> 3x ULN)
  • Active TB during treatment with rifampicin
  • Taking drugs that interact with the drugs of the clinical trial (as specified in the SPC)
  • Pregnancy, breastfeeding or planning to become pregnant during study follow-up
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Burkina Faso,   Côte D'Ivoire,   Senegal,   Togo
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02150993
Other Study ID Numbers  ICMJE ANRS 12294 FIT-2
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Study Sponsor  ICMJE French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Serge P. Eholié, MD, MSc, Pr Service des Maladies Infectieuses et Tropicales, CHU de Treichville, Abidjan, Côte d'Ivoire
Principal Investigator: Françoise P. Brun-Vézinet, MD, MSc, Pr Laboratoire de virologie, Hôpital Bichat-Claude Bernard
PRS Account French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP