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Report for Clinical Trial NCT03299049

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Phase IIIb, Randomized, Multicenter, Parallel-group, Non-inferiority, Open-label Study Evaluating the Efficacy, Safety, and Tolerability of Long-acting Cabotegravir Plus Long-acting Rilpivirine Administered Every 8 Weeks or Every 4 Weeks in HIV-1-infected Adults Who Are Virologically Suppressed

This Antiretroviral Therapy as Long Acting Suppression every 2 Months (ATLAS-2M) study is designed to demonstrate the non-inferior antiviral activity and safety of CAB LA + RPV LA administered every 8 weeks (Q8W) compared to CAB LA + RPV LA administered every 4 weeks (Q4W) over a 48-week treatment period in approximately 1020 adult HIV-1 infected subjects. Subjects will be divided in 2 groups; Group 1 will include subjects receiving current anti-retroviral (ART) standard of care (SOC) therapy whereas group 2 will include subjects currently receiving CAB LA + RPV LA Q4W in ATLAS study. Subjects in both groups will be randomized to receive CAB LA + RPV LA Q4W or Q8W. The study will be carried out in 3 phases including screening phase, maintenance phase and extension phase. Subjects choosing not to enter the Extension phase can complete their study participation at the Week 100 visit and enter into the 52-week Long-Term Follow-Up (LTFU) Phase as required.

NCT03299049 HIV Infections
MeSH:HIV Infections

4 Interventions

Name: Cabotegravir Tablets

Description: CAB tablets are white to almost white oval shaped film coated 30 mg tablets for oral administration. CAB tablets are to be stored up to 30 degree Celsius and protected from moisture.
Type: Drug
Group Labels: 2

Subjects in group 1 receiving study treatment once in 4 weeks Subjects in group 1 receiving study treatment once in 8 weeks

Name: Rilpivirine Tablets

Description: RPV tablets are 25 mg tablets that are off-white, round, biconvex, film-coated and debossed on one side with "TMC" and the other side with "25". RPV tablets should be stored at 25 degree Celsius (excursions permitted to 15 degree-30 degree Celsius) and protected from light.
Type: Drug
Group Labels: 2

Subjects in group 1 receiving study treatment once in 4 weeks Subjects in group 1 receiving study treatment once in 8 weeks

Name: Cabotegravir Injectable Suspension

Description: CAB LA injectable suspension is a sterile white to slightly pink suspension containing 200 mg/mL of GSK1265744 as free acid for administration by IM injection. CAB LA injectable suspension is to be stored at up to 30 degree Celsius and should not be freezed.
Type: Drug
Group Labels: 4

Subjects in group 1 receiving study treatment once in 4 weeks Subjects in group 1 receiving study treatment once in 8 weeks Subjects in group 2 receiving study treatment once in 4 weeks Subjects in group 2 receiving study treatment once in 8 weeks

Name: Rilpivirine Injectable Suspension

Description: RPV LA injectable suspension is a sterile white suspension containing 300 mg/mL of RPV as the free base for administration by IM injection. RPV LA injectable suspension should be kept in the outer package and stored at 2-8 degree Celsius and should not be freezed. RPV LA should also be protected from light.
Type: Drug
Group Labels: 4

Subjects in group 1 receiving study treatment once in 4 weeks Subjects in group 1 receiving study treatment once in 8 weeks Subjects in group 2 receiving study treatment once in 4 weeks Subjects in group 2 receiving study treatment once in 8 weeks


Primary Outcomes

Description: Virologic outcome for each subject will be calculated according to the food and drug administration's (FDA) Snapshot algorithm. As defined by the Snapshot algorithm, HIV-RNA >=50 copies/mL is determined by the last available HIV-1 RNA measurement while the subject is on treatment within the analysis visit window of interest.

Measure: Percentage of subjects with plasma HIV ribonucleic acid (RNA) >=50 copies per milliliter (copies/mL) at Week 48

Time: Week 48

Secondary Outcomes

Description: The antiviral and immunologic activity of CAB LA + RPV LA Q8W will be compared to CAB LA + RPV LA Q4W at Week 24, Week 48 and Week 96 using the FDA Snapshot algorithm. Subjects with last available HIV-1 RNA measurement <50 copies/mL while the subject is on treatment within the analysis visit window of interest are classified as responders; subjects without evaluable HIV-RNA data for the visit of interest or who change treatment not permitted per protocol before the analysis window are considered non-responders.

Measure: Percentage of subjects with plasma HIV-1 RNA <50 copies/mL

Time: Up to Week 96

Description: CVF is defined as rebound as indicated by two consecutive plasma HIV-1 RNA levels >=200 copies/mL after prior suppression to <200 copies/mL. CVF will be analyzed through Week 24, Week 48 and Week 96 as a measure of antiviral and immunologic activity of CAB LA and RPV LA.

Measure: Percentage of subjects with protocol-defined confirmed virologic failure (CVF)

Time: Up to Week 96

Description: Virologic outcome for each subject will be calculated according to the FDA Snapshot algorithm. As defined by the Snapshot algorithm, HIV-RNA >=50 copies/mL is determined by the last available HIV-1 RNA measurement while the subject is on treatment within the analysis visit window of interest.

Measure: Percentage of subjects with HIV-RNA >=50 copies/mL

Time: Up to Week 96

Description: Change from Baseline in viral load will be assessed over time including Week 48 and Week 96.

Measure: Change from Baseline in viral load

Time: Baseline and Up to Week 96

Description: Lymphocyte subsets will be collected for assessment by flow cytometry at specific time points including Week 48 and Week 96.

Measure: Change from Baseline in cluster of differentiation (CD)4+ cell counts

Time: Baseline and Up to Week 96

Description: An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as SAE.

Measure: Number of subjects with Adverse events (AEs) and serious AEs

Time: Up to Week 96

Description: Clinical chemistry parameters including blood urea nitrogen (BUN), creatinine, glucose, sodium, potassium, chloride, total carbon-di-oxide (CO2), lipase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, phosphate, total bilirubin, albumin, creatine phosphokinase and lipid panel will be analyzed as a measure of safety.

Measure: Number of subjects with abnormal clinical chemistry values

Time: Up to Week 96

Description: Clinical hematology parameters including platelet count, red blood cell (RBC) count, white blood cell (WBC) count, hemoglobin, hematocrit, mean corpuscle volume (MCV), neutrophils, lymphocytes, monocytes, eosinophils and basophils will be analyzed as a measure of safety.

Measure: Number of subjects with abnormal clinical hematology values

Time: Up to Week 96

Description: Subjects who discontinue treatment due to AEs will be analyzed as a measure of safety.

Measure: Percentage of subjects who discontinue treatment due to AEs

Time: Up to Week 96

Description: Change from Baseline in albumin will be assessed up to long-term follow-up visits as a measure of safety.

Measure: Change from Baseline in albumin

Time: Baseline and up to Week 96

Description: Change from Baseline in Alkaline phosphatase, ALT, AST, creatine phosphokinase, lipase will be assessed up to long-term follow-up visits as a measure of safety.

Measure: Change from Baseline in Alkaline phosphatase, ALT, AST, creatine phosphokinase, lipase

Time: Baseline and up to Week 96

Description: Change from Baseline in total bilirubin and creatinine will be assessed up to long-term follow-up visits as a measure of safety.

Measure: Change from Baseline in total bilirubin and creatinine

Time: Baseline and up to Week 96

Description: Change from Baseline in glucose, sodium, potassium, total CO2, BUN, chloride, phosphate will be assessed up to long-term follow-up visits as a measure of safety.

Measure: Change from Baseline in glucose, sodium, potassium, total CO2, BUN, chloride, phosphate

Time: Baseline and up to Week 96

Description: Change from Baseline in total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides will be assessed up to long-term follow-up visits as a measure of safety.

Measure: Change from Baseline in total cholesterol, High density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol and triglycerides

Time: Baseline and Up to Week 96

Description: Change from Baseline in creatinine clearance will be assessed up to long-term follow-up visits as a measure of safety.

Measure: Change from Baseline in creatinine clearance

Time: Baseline and Up to Week 96

Description: Change from Baseline in basophils, eosinophils, monocytes, lymphocytes, neutrophils and platelet count will be assessed up to long-term follow-up visits as a measure of safety.

Measure: Change from Baseline in basophils, eosinophils, monocytes, lymphocytes, neutrophils and platelet count

Time: Baseline and Up to Week 96

Description: Change from Baseline in hematocrit levels will be assessed up to long-term follow-up visits as a measure of safety.

Measure: Change from Baseline in hematocrit levels

Time: Baseline and Up to Week 96

Description: Change from Baseline in hemoglobin levels will be assessed up to long-term follow-up visits as a measure of safety.

Measure: Change from Baseline in hemoglobin levels

Time: Baseline and Up to Week 96

Description: Change from Baseline in RBC count will be assessed up to long-term follow-up visits as a measure of safety.

Measure: Change from Baseline in RBC count

Time: Baseline and Up to Week 96

Description: Change from Baseline in WBC count will be assessed up to long-term follow-up visits as a measure of safety.

Measure: Change from Baseline in WBC count

Time: Baseline and Up to Week 96

Description: Change from Baseline in MCV levels will be assessed up to long-term follow-up visits as a measure of safety.

Measure: Change from Baseline in MCV levels

Time: Baseline and Up to Week 96

Description: Whole venous blood samples will be obtained from each subject for analysis of potential genotypic resistance to CAB, RPV.

Measure: Number of incidences of treatment emergent genotypic resistance

Time: Up to Week 96

Description: Whole venous blood samples will be obtained from each subject for analysis of potential phenotypic resistance to CAB, RPV.

Measure: Number of incidences of treatment emergent phenotypic resistance

Time: Up to Week 96

Description: Blood samples will be collected at specific time points for pharmacokinetic analysis of CAB LA.

Measure: Trough plasma concentration (Ctrough) of CAB LA: Q4W dosing

Time: Pre-dose at Week 4B, 8, 16, 24, 32, 40, 48 and 96

Description: Blood samples will be collected at specific time points for pharmacokinetic analysis of RPV LA.

Measure: Ctrough of RPV LA: Q4W dosing

Time: Pre-dose at Week 4B, 8, 16, 24, 32, 40, 48 and 96

Description: Blood samples will be collected at specific time points for pharmacokinetic analysis of CAB LA.

Measure: Ctrough of CAB LA: Q8W dosing

Time: Pre-dose at Week 8, 9, 16, 24, 32, 40, 41, 48 and 96

Description: Blood samples will be collected at specific time points for pharmacokinetic analysis of RPV LA.

Measure: Ctrough of RPV LA: Q8W dosing

Time: Pre-dose at Week 8, 9, 16, 24, 32, 40, 41, 48 and 96

Description: Blood samples will be collected at specific time points for pharmacokinetic analysis of CAB LA.

Measure: Maximum plasma concentration (Cmax) of CAB LA: Q4W dosing

Time: Pre-dose at Week 4B, 8, 16, 24, 32, 40, 48 and 96

Description: Blood samples will be collected at specific time points for pharmacokinetic analysis of RPV LA.

Measure: Cmax of RPV LA: Q4W dosing

Time: Pre-dose at Week 4B, 8, 16, 24, 32, 40, 48 and 96

Description: Blood samples will be collected at specific time points for pharmacokinetic analysis of CAB LA.

Measure: Cmax of CAB LA: Q8W dosing

Time: Pre-dose at Week 8, 9, 16, 24, 32, 40, 41, 48 and 96

Description: Blood samples will be collected at specific time points for pharmacokinetic analysis of RPV LA.

Measure: Cmax of RPV LA: Q8W dosing

Time: Pre-dose at Week 8, 9, 16, 24, 32, 40, 41, 48 and 96

Description: Blood samples will be collected at specific time points for pharmacokinetic analysis of CAB LA.

Measure: Area under the curve (AUC) of CAB LA: Q4W dosing

Time: Pre-dose at Week 4B, 8, 16, 24, 32, 40, 48 and 96

Description: Blood samples will be collected at specific time points for pharmacokinetic analysis of RPV LA.

Measure: AUC of RPV LA: Q4W dosing

Time: Pre-dose at Week 4B, 8, 16, 24, 32, 40, 48 and 96

Description: Blood samples will be collected at specific time points for pharmacokinetic analysis of CAB LA.

Measure: AUC of CAB LA: Q8W dosing

Time: Pre-dose at Week 8, 9, 16, 24, 32, 40, 41, 48 and 96

Description: Blood samples will be collected at specific time points for pharmacokinetic analysis of RPV LA.

Measure: AUC of RPV LA: Q8W dosing

Time: Pre-dose at Week 8, 9, 16, 24, 32, 40, 41, 48 and 96

Description: Demographic parameters including, but not limited to, age, sex, race, body weight, body mass index, and relevant laboratory parameters will be evaluated as potential predictors of inter participant variability for pharmacokinetic parameters.

Measure: Number of subjects with different demographic parameters: For inter-participant variability

Time: Up to Week 96

Description: Demographic parameters including, but not limited to, age, sex, race, body weight, body mass index, and relevant laboratory parameters will be evaluated as potential predictors of inter participant variability for pharmacokinetic parameters.

Measure: Number of subjects with different demographic parameters: For intra participant variability

Time: Up to Week 96

Description: The HAT-QoL is a 42-item questionnaire grouped into nine dimensions, assessing overall function and well-being. A shorter version of this original HAT-QoL will be used in the present study which will contain 14-items grouped into the three following dimensions: "life satisfaction", "disclosure worries" and "HIV medication". All items use a ''past 4 weeks'' timeframe and a Likert response scale from 1=''all of the time'' to 5=''none of the time''.

Measure: Change from Baseline in health related quality of life (HRQoL) of subjects using the HIV/Acquired immunodeficiency syndrome (AIDS) Targeted Quality of Life (HAT-QoL) questionnaire

Time: Baseline and up to Week 48

Description: HIVTSQ is a 10-item questionnaire which is used specifically to measure satisfaction with medication for people infected with HIV.

Measure: Change from Baseline in total "treatment satisfaction" score of the HIV Treatment Satisfaction Status Questionnaire (HIVTSQs)

Time: Baseline and up to Week 48

Description: HIVTSQ is a 10-item questionnaire which is used specifically to measure satisfaction with medication for people infected with HIV.

Measure: Change from Baseline in individual item score of HIVTSQs

Time: Baseline and Up to Week 48

Description: HIVTSQc is the change version of original HIVTSQs. HIVTSQc enhances the sensitivity by allowing those who were satisfied at Baseline to express even greater satisfaction at follow-up.

Measure: Change in treatment satisfaction using the HIV Treatment Satisfaction Change Questionnaire (HIVTSQc)

Time: Week 48

Description: Change from Week 8 in dimension score which assess Bother of Injection Site Reactions (ISRs), Leg movement, Sleep, and Injection Acceptance will be evaluated using PIN questionnaire. This measure contains 21 items and scores range from 1 to 5 where 1= the most favorable perception of vaccination while 5= the most unfavorable.

Measure: Change from Week 8 in Dimension scores using the Perception of injection questionnaire (PIN)

Time: Week 8 and up to Week 48

Description: Change from Week 8 in individual item scores which assess pain during injection, anxiety before and after injection, willingness to be injected in the future and overall satisfaction with mode of administration over time will be evaluated using the PIN questionnaire. This measure contains 21 items and scores range from 1 to 5 where 1= the most favorable perception of vaccination while 5= the most unfavorable.

Measure: Change from Week 8 in individual item score using PIN

Time: Week 8 and Up to Week 48

Description: The ACCEPT questionnaire, a 25 item questionnaire, is a generic medication acceptance measure assessing how patients weigh advantages and disadvantages of long-term medications. The study will use three questions that focus on general acceptance of study medication.

Measure: Change from Baseline in treatment acceptance using the "General acceptance" dimension of the Chronic Treatment Acceptance (ACCEPT) questionnaire

Time: Baseline and up to Week 48

Description: Lymphocyte subsets will be collected for assessment by flow cytometry at specific time points including Week 48 and Week 96.

Measure: CD4+ cell counts

Time: Baseline and up to Week 96

Description: The preference questionnaire will include 3 questions evaluating preference of HIV treatment and the attributes supporting this preference. It will assess will assess whether subjects prefer the CAB LA + RPV LA injectable treatment.

Measure: Number of subjects preferring CAB LA+ RPV LA injectable treatment, using preference questionnaire

Time: Week 48

Description: The preference questionnaire will include 3 questions evaluating preference of HIV treatment and the attributes supporting this preference. It will assess will assess whether subjects prefer the CAB LA + RPV LA Q8W injectable treatment.

Measure: Number of subjects preferring CAB LA + RPV LA Q8W, using preference questionnaire

Time: Week 48

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 K103N

- Any evidence of primary resistance based on the presence of any major known Integrase inhibitor (INI) or Non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance-associated mutation, except for K103N by any historical resistance test result. --- K103N ---



HPO Nodes