Efficacy and Safety of a Dolutegravir-based Regimen for the Initial Management of HIV Infected Adults in Resource-limited Settings

HIV-1 Infection Clinical Trial

— NAMSAL  

Official title:

A Phase III Randomized, Open Label Trial to Evaluate Dolutegravir Versus Efavirenz 400 mg, Both Combined With Tenofovir Disoproxil Fumarate + Lamivudine for the Initial Management of HIV Infected Adults in Resource-limited Settings

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02777229
• Other study ID #: ANRS 12313 NAMSAL
• Status: Completed
• Phase: Phase 3
• Start date: July 2016
• Est. completion date: July 2021

Study information

• Verified date: February 2021
• Source: ANRS, Emerging Infectious Diseases
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Several reports indicate that treatment failure due to HIV resistance or to adverse event-related discontinuation could compromise the effectiveness of scaling-up antiretroviral treatment (ART), especially when lack of access to viral load is a concern. Combined with other nucleoside reverse transcriptase inhibitor, Dolutegravir (DTG) is a very promising alternative to the current first-line non nucleoside reverse transcriptase inhibitor-based regimens.

Initial evaluations of DTG conducted in high income countries showed excellent efficacy and safety and indicated high genetic barrier thus preserving second line treatment. As a consequence, DTG-based regimens have been recently included in the first-line options in the national guidelines for ART of several high-income countries. However, the clinical trials evaluating DTG-based regimens have been conducted in highly controlled conditions, including baseline resistance testing and regular viral load monitoring. Moreover, these trials included a high proportion of men with rare co-morbidities.

There is need to evaluate how a DTG-based regimen will perform in real-world conditions within resources-constrained settings, where viral load monitoring is limited, and where the majority of HIV patients are women with important family planning consideration and NAMSAL trial is a randomized clinical trial which aims to evaluate efficacy and safety over 48, 96 and 192 weeks of DTG + tenofovir disoproxil fumarate/lamivudine versus Efavirenz (EFV) + tenofovir disoproxil fumarate/lamivudine in 606 ART-naïve HIV-1-infected adults in Cameroon. A set of efficacy and safety endpoints will be compared over 48, 96 and 192 weeks between the two arms including the proportion of patients with viral load <50 copies/mL and incidence of severe adverse events.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 616
• Est. completion date: July 2021
• Est. primary completion date: July 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• HIV-1 infected

• Age = 18 years

• Abtiretroviral-naïve, including above 7 days of cumulative prior antiretroviral therapy at any time prior to study entry.

• For women of childbearing potential: acceptance to use effective contraceptive methods

• Provision of written informed consent

Exclusion Criteria:

• Infection with HIV-1 group O, N, P

• Infection or co-infection with HIV-2

• Absolute neutrophil count (ANC) < 500 cells/mm3

• Hemoglobin < 7.0 g/dL

• Platelet count < 50,000 cells/mm3

• AST and/or ALT > 5 x Upper Limit of Normal (ULN)

• Calculated creatinine clearance < 50 mL/min

• Active opportunistic or severe disease not under adequate control

• For women of childbearing age : Pregnancy/breastfeeding

• History or presence of allergy and/or contraindications to the trial drugs or their components

• Severe psychiatric illness

• Severe hepatic failure Patients co-infected with tuberculosis (TB), receiving a TB treatment and with stable clinical condition will not be excluded.

Related Conditions & MeSH terms

• HIV-1 Infection

Intervention

Drug:
• Dolutegravir 50 mg
1 tablet once a day
• Tenofovir disoproxil fumarate 300 mg / lamivudine 300 mg
Fixed dose combination, 1 tablet once a day
• Efavirenz 400 mg
1 tablets once a day

Locations

Country	Name	City	State
Cameroon	Cité verte Hospital	Yaoundé
Cameroon	Hopital Central	Yaoundé
Cameroon	Military Hospital	Yaoundé

Sponsors (3)

Lead Sponsor	Collaborator
ANRS, Emerging Infectious Diseases	Institut de Recherche pour le Developpement, UNITAID

Country where clinical trial is conducted

Cameroon, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients with Viral Load (VL) <50 cp/mL	Proportion of patients with Viral Load (VL) <50 cp/mL at week 48 (FDA snapshot algorithm)	week 48
Secondary	Proportion of patients with Viral Load (VL) <50 cp/mL	Proportion of patients with Viral Load (VL) <50 cp/mL at week 96 (FDA snapshot algorithm)	week 96
Secondary	Proportion of patients with Viral Load (VL) <50 cp/mL	Proportion of patients with VL< 50 cp/mL at week 24 (FDA snapshot algorithm)	week 24
Secondary	Proportion of patients with Viral Load (VL) < 200 cp/mL	Proportion of patients with VL< 200 cp/mL (FDA snapshot algorithm)	week 24, week 48, week 96, week 144, week 192
Secondary	Time to virologic failure	Time to virologic failure	week 48, week 96, week 144, week 192
Secondary	Changes in Cluster of differentiation 4 (CD4)-cell count from baseline to endpoints week-48, -96, -144, -192	Changes in Cluster of differentiation 4 (CD4)-cell count from baseline to endpoints week-48, -96, -144, -192	Baseline, week 48, week 96, week 144, week 192
Secondary	Time to death or to disease progression	Time to death or to disease progression	week 48, week 96, week 144, week 192
Secondary	Time to first toxicity failure	Time to first toxicity failure	week 48, week 96, week 144, week 192
Secondary	Incidence of first grade 3 or 4 clinical adverse event	Incidence of first grade 3 or 4 clinical adverse event	week 48, week 96, week 144, week 192
Secondary	Incidence of first grade 3 or 4 laboratory adverse event	Incidence of first grade 3 or 4 laboratory adverse event	week 48, week 96, week 144, week 192
Secondary	AE and SAE	Incidence of adverse events (AE) and serious adverse event (SAE)	week 48, week 96, week 144, week 192
Secondary	Time to treatment discontinuation	Time to treatment discontinuation	week 48, week 96, week 144, week 192
Secondary	Hemoglobine changes from baseline to endpoints week-48, -96, -144, -192	Changes in hemoglobin Time to virologic failure from baseline to endpoints week-48, -96, -144, -192	Baseline, week 48, week 96, week 144, week 192
Secondary	Changes in creatinine from baseline to endpoints week-48, -96, -144, -192	Changes in creatinine from baseline to endpoints week-48, -96, -144, -192	Baseline, week 48, week 96, week 144, week 192
Secondary	Changes in estimated glomerular filtration rate from baseline to endpoints week-48, -96, -144, -192	Changes in estimated glomerular filtration rate from baseline to endpoints week-48, -96, -144, -192	Baseline, week 48, week 96, week 144, week 192
Secondary	Changes in Aspartate Aminotransferase (AST) ffrom baseline to endpoints week-48, -96, -144, -192	Changes in Aspartate Aminotransferase (AST) from baseline to endpoints week-48, -96, -144, -192	Baseline, week 48, week 96, week 144, week 192
Secondary	Changes in Alanine Aminotransferase (ALT) from baseline to endpoints week-48, -96, -144, -192	Changes in Alanine Aminotransferase (ALT) from baseline to endpoints week-48, -96, -144, -192	Baseline, week 48, week 96, week 144, week 192
Secondary	Changes in level of fasting glucose from baseline to endpoints week-48, -96, -144, -192	Changes in level of fasting glucose from baseline to endpoints week-48, -96, -144, -192	Baseline, week 48, week 96, week 144, week 192
Secondary	Changes in level of total cholesterol from baseline to endpoints week-48, -96, -144, -192	Changes in level of total cholesterol from baseline to endpoints week-48, -96, -144, -192	Baseline, week 48, week 96, week 144, week 192
Secondary	Changes in level of triglycerides from baseline to endpoints week-48, -96, -144, -192	Changes in level of triglycerides from baseline to endpoints week-48, -96, -144, -192	Baseline, week 48, week 96, week 144, week 192
Secondary	Changes in level of HDL from baseline to endpoints week-48, -96, -144, -192	Changes in level of HDL from baseline to endpoints week-48, -96, -144, -192	Baseline, week 48, week 96, week 144, week 192
Secondary	Proportion of patients defaulting clinic schedule	Proportion of patients defaulting clinic schedule	week 48, week 96, week 144, week 192
Secondary	Mean medication adherence level from baseline to endpoints week-48, -96, -144, -192	Mean medication adherence level from baseline to endpoints week-48, -96, -144, -192	week 48, week 96, week 144, week 192
Secondary	Mean change in Depression Anxiety Stress Scale from baseline to endpoints week-48, -96, -144, -192	Mean change in Depression Anxiety Stress Scale from baseline to endpoints week-48, -96, -144, -192; Depression Normal 0-9, Mild 10-13, Moderate 14-20, Severe 21-27, Extremely Severe +28; Anxiety Normal 0-7, Mild 8-9, Moderate 10-14, Severe 15-19, Extremely Severe +20; Stress Normal 0-14, Mild 15-18, Moderate 19-25, Severe 26-33, Extremely Severe +34	Baseline, week 48, week 96, week 144, week 192
Secondary	Mean change in Quality of life score assessed by the Short Form health survey from baseline to endpoints week-48, -96, -144, -192	Mean change in Quality of life score assessed by the Short Form health survey from baseline to endpoints week-48, -96, -144, -192 (Score varies according to the items, in order to test the vigilance of the patient. Reading the results provides a semantic appreciation)	Baseline, week 48, week 96, week 144, week 192
Secondary	Mean change in EFV-related symptoms questionnaire score from baseline to endpoints week-48, -96, -144, -192	Mean change in EFV-related symptoms questionnaire score from baseline to endpoints week-48, -96, -144, -192	Baseline, week 48, week 96
Secondary	Tobacco status consumtion	The status of tobacco smoker / non-smoker will be requested.	week 192
Secondary	HbA1c	Levels of glycated hemoglobin	week 192
Secondary	hsPCR	Levels of high sensitivity protein C reactive	week 192
Secondary	Lipodistrophia	Qualitative and quantitative measurements of soft tissue composition = Lipodistrophia	week 192
Secondary	CIMT	Mesures of Carotid Intima-Media Thickness	week 192
Secondary	PWV	Mesures of Pulse Wave Velocity	week 192
Secondary	Levels of adiponectin	Levels of adiponectin	Baseline, week 48, week 96, week 144, week 192
Secondary	Levels of leptin	Levels of leptin	Baseline, week 48, week 96, week 144, week 192
Secondary	Levels of ghrelin	Levels of ghrelin	Baseline, week 48, week 96, week 144, week 192