SNPMiner Trials by Shray Alag


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Report for Mutation Q148R

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 3 clinical trials

Clinical Trials


1 Dolutegravir + Rilpivirine Switch Study (DORISS): Pilot and Noninferiority Trial Comparing Dolutegravir + Rilpivirine vs. Continued HAART (Highly Active Antiretroviral Therapy) in Patients With Plasma HIV RNA ≤ 50 Copies/mL for at Least 2 Years

The primary objective of the study is to evaluate the capacity of Dolutegravir + Rilpivirine vs. continued triple combination HAART to maintain plasma HIV RNA ≤ 50 copies/ml throughout 24 weeks in patients with plasma HIV RNA ≤ 50 copies/mL for at least 2 years under conventional HAART (2 NNRTI + 3rd agent). The main secondary objectives are the following: - % of virologic success (plasma viral load ≤ 50 copies/mL) at W24 and W48 - % of patients who maintain a plasma viral load ≤ 50 copies / ml from D0 to W48 - % of virological failure defined by two consecutive plasma viral load > 50 copies/mL - Profile of genotypic resistance in case of virological failure. The trial will be conducted according to the design below, in 3 steps: - Step 1: enrollment of 80 patients (40 in each arm) - Step 2: enrollment on hold until W16 data from the 40 patients enrolled in the intervention arm have been analyzed. - Step 3: resumption and completion of enrollment if conditions for resuming enrollment at the end of step 2 are fulfilled, i.e. if the percentage of patients randomized to the intervention arm who have a plasma viral load ≤ 50 copies/mL from D0 to W16 is significantly > 70%, which translates in a maximum of 6 virologic failures.

NCT02069834 HIV Infection HAART-treated Virologically Controlled Drug: Arm 1 (intervention) Drug: Arm 2 (control)
MeSH:HIV Infections

- No mutation (either on pre-ART genotype or on DNA genotype at screening) among the following: T66K, G118R, V151L, S153F/Y, R263K, T66K + L74M, E92Q + N155H, Q148R +N155H, Q148H/K/R with at least one mutation of L74I or E138A/K/T or G140A/C/S - Negative HBs Ag - Informed consent form signed by patient and investigator - A specific consent for the pharmacokinetic substudy will be signed by the 10 patients of the pilot phase of the trial who will be randomized to the Dolutegravir + Rilpivirine arm and will volunteer for this PK study - Patient covered with health insurance - Effective contraception Exclusion Criteria: - HIV-2 infection - Dialysis or severe renal failure (creatinine clearance < 30 ml/min) - History of decompensated liver disease - History of HIV-associated neurocognitive disorders - AST or ALT > 5 x ULN - Positive HBc Ac and negative HBs Ac - Patient receiving a proton pump inhibitor that cannot be switched to another anti-secretory drug - Current pregnancy or breastfeeding - Patient involved in another research that precludes enrolment in another trial - Patient under guardianship, or deprived of liberty by a court or administrative decision. --- T66K --- --- G118R --- --- V151L --- --- S153F --- --- R263K --- --- T66K --- --- L74M --- --- E92Q --- --- N155H --- --- Q148R ---

Primary Outcomes

Measure: Pilot phase: Percentage of patients with plasma viral load ≤ 50 copies HIV-RNA/ml from D0 (Day 0) to W16 (Week 16)

Time: Week 16

Measure: Non-inferiority phase: Percentage of patients with plasma HIV RNA maintained ≤ 50 copies/mL throughout 24 weeks

Time: Week 24

Secondary Outcomes

Measure: Percentage of patients with plasma viral load ≤50 HIV RNA copies/mL at Week 24 and Week 48

Time: Week 48

Measure: Percentage of patients with plasma viral load ≤50 HIV RNA copies/mL from Day 0 to Week 48

Time: Week 48

Measure: Percentage of virologic failure, defined as 2 consecutive plasma HIV RNA > 50 copies/mL

Time: Week 48

Measure: Measure of the profile of genotypic resistance in plasma in case of virologic failure

Time: Week 48

Measure: Percentage of patients who discontinued or changed the strategy of the study

Time: Week 48

Description: Evolution of the HIV-DNA between Day 0 and week 48

Measure: Measure of the HIV-DNA between day 0 and week 48

Time: W48

Description: Evolution of CD4 lymphocytes (average) at Week 24 compared to Day 0

Measure: Measure of CD4 lymphocytes at week 24 compared to day 0

Time: Week 24

Description: Evolution of CD4 lymphocytes (average) at Week 48 compared to Day0

Measure: Measure of CD4 lymphocytes at Week 48 compared to Day 0

Time: Week 48

Description: Adverse events : incidence, grade and relation to study medication of all adverse events, of grade 2 to 4 events

Measure: Number of patients with adverse events of grade 2 to 4

Time: Week 48

Description: Mean changes in serum plasma lipid parameters at Week 24 compared to Day 0

Measure: Measure of changes in serum plasma lipid parameters at week 24 compared to Day 0

Time: Week 24

Description: Mean changes in serum plasma lipid parameters at Week 48 compared to Day 0

Measure: Measure of changes in serum lipid parameters at week 48 to Day 0

Time: Week 48

Description: Changes in fat mass distribution at Week 24 compared to Day 0

Measure: Measure of changes in fat mass distribution at week 24 compared to Day 0

Time: Week 24

Description: Changes in fat mass distribution at Week 48 compared to Day 0

Measure: Measure of changes in fat mass distribution at Week 48 compared to Day 0

Time: Week 48

Description: Evolution of adherence to treatment at Week 24 compared to Day 0 assessed by a validated questionnaire

Measure: Measure of adherence to treatment at Week 24 compared to Day 0

Time: Week 24

Description: Evolution of adherence to treatment at Week 48 compared to Day 0 assessed by a validated questionnaire

Measure: Measure of adherence to treatment at Week 48 compared to Day 0

Time: Week 48

Description: Assessment of patient satisfaction for their treatment at D0 by questionnaire

Measure: Measure of patient satisfaction for their treatment at Day 0

Time: Day 0

Description: Assessment of patient satisfaction for their treatment at Week 24 by questionnaire

Measure: Measure of patient satisfaction for their treatment at Week 24

Time: Week 24

Description: Assessment of patient satisfaction for their treatment at Week 48 by questionnaire

Measure: Measure of patient satisfaction for their treatment at Week 48

Time: Week 48

Description: Changes in plasma biomarkers of inflammation (hs-CRP and IL-6) and immune activation (sCD14 , MCP -1, IP10 ) at Week 24 compared to Day 0 .

Measure: Measure of changes in plasma biomarkers of inflammation (hs-CRP and IL-6) and immune activation (sCD14 , MCP -1, IP10 ) at Week 24 compared to Day 0 .

Time: Week 24

Description: Changes in plasma biomarkers of inflammation (hs-CRP and IL-6) and immune activation (sCD14 , MCP -1, IP10 ) at Week 48 compared to Day 0 .

Measure: Measure of changes in plasma biomarkers of inflammation (hs-CRP and IL-6) and immune activation (sCD14 , MCP -1, IP10 ) at Week 48 compared to Day 0 .

Time: Week 48

Description: Analysis PK (PharmacoKinetic) / PD (Pharmaodynamic) of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 4

Measure: Measure of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 4

Time: Week 4

Description: Analysis PK / PD of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 24

Measure: Measure of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 24

Time: Week 24

Measure: Measure of the profile of genotypic resistance in plasma in case of virologic failure

Time: Week 24

Measure: Percentage of virologic failure, defined as 2 consecutive plasma HIV RNA > 50 copies/mL

Time: Week 24

2 A Phase 2b/3 Double Blind Safety and Efficacy Study of Injectable Cabotegravir Compared to Daily Oral Tenofovir Disoproxil Fumarate/Emtricitabine (TDF/FTC), For Pre-Exposure Prophylaxis in HIV-Uninfected Cisgender Men and Transgender Women Who Have Sex With Men

This study will evaluate the safety and efficacy of the injectable drug cabotegravir (CAB LA), for pre-exposure prophylaxis (PrEP) in HIV-uninfected cisgender men and transgender women who have sex with men (MSM and TGW).

NCT02720094 HIV Infections Drug: Cabotegravir tablets Drug: TDF/FTC tablets Drug: TDF/FTC placebo tablets Drug: CAB placebo tablets Drug: CAB LA Drug: Placebo for CAB LA
MeSH:HIV Infections

Incidence of resistance mutations to study products (including but not limited to K65R, M184V/I, Q148R) among seroconverters. --- K65R --- --- M184V --- --- Q148R ---

Primary Outcomes

Measure: Number of documented incident HIV infections in Steps 1 and 2

Time: Measured through participant's last study visit, up to 4 years after study entry

Measure: Number of Grade 2 or higher clinical and laboratory adverse events

Time: Measured through participant's last study visit, up to 4 years after study entry

Secondary Outcomes

Measure: Number of documented incident HIV infections in Step 2

Time: Measured through participant's last study visit, up to 4 years after study entry

Measure: Number of documented incident HIV infections in Steps 1, 2, and 3

Time: Measured through participant's last study visit, up to 4 years after study entry

Measure: Number of documented incident HIV infections in Step 3

Time: Measured through participant's last study visit, up to 4 years after study entry

Measure: Number of documented incident HIV infections in Step 2 and 3

Time: Measured through participant's last study visit, up to 4 years after study entry

Measure: Changes from baseline in creatinine and creatinine clearance levels

Time: Measured through participant's last study visit, up to 4 years after study entry

Description: (laboratory assessment of alanine aminotransferase (ALT), aspartate aminotransferase (AST), TBili, creatine phosphokinase (CPK), or clinical assessment of jaundice/icterus).

Measure: Number of Grade 3 or 4 liver-related adverse events (AEs)

Time: Measured through participant's last study visit, up to 4 years after study entry

Measure: Changes in Z-score from baseline and DXA criteria for osteopenia and osteoporosis

Time: Measured through participant's last study visit, up to 4 years after study entry

Measure: Incidence of resistance mutations to study products (including but not limited to K65R, M184V/I, Q148R) among seroconverters

Time: Measured through participant's last study visit, up to 4 years after study entry

Description: Based on physical examination

Measure: Changes in weight from baseline

Time: Measured through participant's last study visit, up to 4 years after study entry

Description: Based on physical examination

Measure: Changes in blood pressure from baseline

Time: Measured through participant's last study visit, up to 4 years after study entry

Description: Based on physical examination

Measure: Changes in pulse rate from baseline

Time: Measured through participant's last study visit, up to 4 years after study entry

Description: Based on laboratory evaluations

Measure: Changes in fasting glucose levels from baseline

Time: Measured through participant's last study visit, up to 4 years after study entry

Description: Based on laboratory evaluations

Measure: Changes in fasting lipid profile from baseline

Time: Measured through participant's last study visit, up to 4 years after study entry

3 A Single-Dose Clinical Trial to Study the Safety, Tolerability, Pharmacokinetics, and Anti-Retroviral Activity of MK-4250 Monotherapy in Anti-Retroviral Therapy (ART)-Naive, HIV-1 Infected Subjects

The study will evaluate the safety, tolerability, pharmacokinetics, and anti-retroviral activity of MK-4250 monotherapy in anti-retroviral therapy (ART)-naïve, HIV-1 infected participants. The primary hypothesis of the study is that at a dose that is sufficiently safe and generally well tolerated, MK-4250 has superior antiretroviral activity compared to a historical placebo, as measured by change from baseline in plasma HIV-1 ribonucleic acid (RNA) (log10 copies/mL) at 168 hours postdose.

NCT03351699 HIV-1 Infection Drug: MK-4250

- No evidence at screening for mutations (e.g., E92Q, N55H, Q148K, Q148R and Y143R) affecting susceptibility to Integrase Strand Transfer Inhibitors (InSTIs) - Diagnosed with HIV-1 infection ≥ 3 months prior to screening or confirmed chronic HIV infection - Screening plasma Cluster of Differentiation (CD) 4+ T cell count of >200/mm^3 - Screening plasma HIV-1 RNA ≥5,000 copies/mL within 30 days prior to the treatment phase of this study - Anti-retroviral therapy (ART)-naïve, which is defined as having never received any antiretroviral agent OR ≤30 consecutive days of an investigational antiretroviral agent which is not an InSTI and no exposure to such an investigational antiretroviral agent within 60 days prior to screening OR ≤60 consecutive days of combination ART which does not include an InSTI and no exposure to such ART within 60 days prior to screening - Never received any InSTI - Willing to receive no other ART for the duration of the treatment phase of this study - Body Mass Index (BMI) ≤35 kg/m^2 - Other than HIV infection, have baseline health judged to be stable Exclusion Criteria: - Mentally or legally institutionalized / incapacitated, or significant emotional problems at the time of pretrial (screening) visit or expected during the conduct of the trial or has a history of clinically significant psychiatric disorder within the last 5 years - History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological (outside of HIV-1 infection), renal, respiratory, genitourinary or major neurological abnormalities or diseases - History of cancer (malignancy). --- E92Q --- --- N55H --- --- Q148K --- --- Q148R ---

Primary Outcomes

Description: Plasma HIV-1 RNA was measured at Baseline and 168 hours after dosing. The log10 plasma HIV-RNA copies/mL measurements from participants in each panel were pooled and analyzed based on a longitudinal data analysis model. The change from Baseline in plasma HIV-1 RNA in participants administered MK-4250 was compared with historical placebo data.

Measure: Change From Baseline in Plasma HIV-1 RNA Copies Per mL at 168 Hours

Time: Baseline and Day 7

Description: The percentage of participants experiencing ≥1 AE was calculated. An AE was defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy could be determined.

Measure: Percentage of Participants Experiencing ≥1 Adverse Events (AE)

Time: Up to Day 14

Description: The percentage of participants who discontinued from the study due to an adverse event was calculated. An AE was defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy could be determined.

Measure: Percentage of Participants Who Discontinued Study Due to an Adverse Event (AE)

Time: Up to Day 14

Secondary Outcomes

Description: The area under the concentration-time curve up to the last measurable concentration (AUC0-last) of MK-4250 in plasma was calculated.

Measure: Area Under the Concentration-Time Curve From 0 to Last Measurable Concentration (AUC0-last) for MK-4250

Time: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, 192, and 240 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time, and no 240-hour postdose time.

Description: The area under the concentration-time curve extrapolated to infinity (AUC0-inf) of MK-4250 in plasma was calculated.

Measure: Area Under the Concentration-Time Curve From 0 to Infinity (AUC0-inf) for MK-4250

Time: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, 192, and 240 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time, and no 240-hour postdose time.

Description: The area under the concentration-time curve up to 168 hours (AUC0-168) of MK-4250 in plasma was calculated.

Measure: Area Under the Concentration-Time Curve From 0 to 168 Hours (AUC0-168) for MK-4250

Time: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, and 168 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time.

Description: The maximum concentration (Cmax) of MK-4250 in plasma was observed.

Measure: Maximum Concentration (Cmax) of MK-4250 Reached in Plasma

Time: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, 192, and 240 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time, and no 240-hour postdose time.

Description: The concentration of MK-4250 at 168 hours postdose (C168hr) was observed.

Measure: Concentration of MK-4250 at 168 Hours (C168hr)

Time: 168 hours after administration of MK-4250.

Description: The apparent terminal half-life (t1/2) of MK-4250 in plasma was calculated.

Measure: Apparent Terminal Half-life (t1/2) of MK-4250

Time: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, 192, and 240 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time, and no 240-hour postdose time.

Description: The apparent clearance (CL/F) of MK-4250 in plasma was calculated.

Measure: Apparent Clearance (CL/F) of MK-4250

Time: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, 192, and 240 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time, and no 240-hour postdose time.

Description: The apparent volume of distribution (Vz/F) of MK-4250 in plasma was calculated.

Measure: Apparent Volume of Distribution (Vz/F) of MK-4250

Time: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, 192, and 240 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time, and no 240-hour postdose time.

Description: The time to maximum concentration (Vz/F) of MK-4250 in plasma was calculated.

Measure: Time to Maximum Concentration (Tmax) of MK-4250 Reached in Plasma

Time: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, 192, and 240 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time, and no 240-hour postdose time.


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