A Study to Determine the Safety and Efficacy of Rilpivirine in Treatment-naive Indian Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Infection (RISE)
Primary Purpose
Human Immunodeficiency Virus Infections
Status
Terminated
Phase
Phase 3
Locations
India
Study Type
Interventional
Intervention
Rilpivirine 25 mg
Tenofovir Disoproxil Fumarate (TDF)/Lamivudine (3TC)
Sponsored by
About this trial
This is an interventional treatment trial for Human Immunodeficiency Virus Infections focused on measuring Treatment-naive, rilpivirine, India
Eligibility Criteria
Inclusion Criteria:
- Must have documented human immunodeficiency virus type 1 (HIV-1) infection
- Must be antiretroviral (ARV) treatment-naïve
- Have plasma HIV-1 ribonucleic acid (RNA) less than (<) 100,000 copies/milliliter (mL) at screening visit
- Have cluster of CD4+ T-cell count (greater than) >200/ cubic millimeter (mm^3) at screening visit
- Women of childbearing potential must have a negative serum (beta human chorionic gonadotropin [beta hCG]) pregnancy test at screening; and a negative urine (or serum, if required by local regulations) pregnancy test before the first dose of study
Exclusion Criteria:
- History of any primary nucleo(t)side reverse transcriptase inhibitor (N[t]RTI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations (if testing performed locally, and results are available), as defined by the current International AIDS (acquired immunodeficiency syndrome) Society-United States (USA) (International Antiviral Society-USA) 2017 guidelines
- Has clinical or laboratory evidence of significantly decreased hepatic function or decompensation, irrespective of liver enzyme levels (hepatic insufficiency)
- Diagnosed with acute viral hepatitis at screening or before baseline
- Infected with Mycobacterium tuberculosis which is likely to require rifampicin-based treatment during the study
- Has a Grade 3 or 4 laboratory abnormality as defined by the Division of AIDS (DAIDS) for Grading the Severity of Adult and Pediatric Adverse Events criteria with the following exceptions unless clinical assessment foresees an immediate health risk to the participant: (a) Preexisting diabetes or with asymptomatic glucose Grade 3 or 4 elevations (b) Asymptomatic triglyceride or cholesterol elevations of Grade 3 or 4
Sites / Locations
- St.Johns Medical College and Hospital
- Chennai Antiviral Research and Treatment(CART) Clinical Research Site
- YRGCARE
- Manipal University-Kasturba Medical College
- Lata Mangeshkar Hospital
- Deenanath Mangeshkar Hospital and Research Centre
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment: Rilpivirine+Combination Therapy (TDF/3TC)
Arm Description
The participants will receive antiretroviral treatment of rilpivirine 25 milligram (mg) tablet orally once daily from Day 1 for 48 weeks with a meal to improve absorption. The participants will also receive background combination therapy of 1 tablet orally once daily containing 300 mg tenofovir disoproxil fumarate (TDF) and 300 mg lamivudine (3TC).
Outcomes
Primary Outcome Measures
Percentage of Participants who are Virologic Responders (HIV-1 RNA <400 Copies/mL) at Week 24
Virologic responders are defined as participants having viral load (plasma Human Immunodeficiency Virus-Type 1 Ribonucleic Acid [HIV-1 RNA] levels) less than (<) 400 copies/milliliter (mL) at Week 24 (Food and Drug Administration [FDA]-defined snapshot analysis).
Secondary Outcome Measures
Percentage of Participants who are Virologic Responders (HIV-1 RNA <50 Copies/mL) at Week 24
Virologic responders are defined as participants having viral load (plasma HIV-1 RNA levels) <50 copies/mL at Week 24 (FDA-defined snapshot analysis).
Percentage of Participants who are Virologic Responders (Plasma HIV-1 RNA Levels <50, <400 and <1,000 Copies/mL) at Week 48
Virologic responders are defined as participants having viral load (plasma HIV-1 RNA levels) <50, <400 and <1,000 copies/mL at Week 48 (FDA-defined snapshot analysis).
Absolute Value in Cluster of Differentiation 4 Positive (CD4+) T-Cell Count at Weeks 24 and 48
CD4+T cell absolute counts will be determined at Weeks 24 and 48.
Change from Baseline in CD4+ T Cell Count at Weeks 24 and 48
Change from baseline in CD4+ T cell count will be determined at Weeks 24 and 48.
Percentage of Participants with Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Participants Experiencing Premature Discontinuation due to AEs Through Week 48
Percentage of participants with Grade 3 and 4 AEs will be assessed. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Percentage of participants who prematurely discontinued study due to AEs will also be analyzed.
Percentage of Participants with Laboratory Abnormalities
Percentage of participants with laboratory abnormalities will be reported.
Number of Participant with Clinically Significant Change from Baseline in Laboratory Parameters
Number of participants with clinically significant change from baseline in laboratory parameters related to hematology, serum chemistry will be assessed.
Emergence of Viral Resistance Through Weeks 24 and 48
Resistance analysis will be determined using genotypic analysis at the time of virological failure (that is, 2 consecutive plasma HIV-1 RNA levels greater than or equal to [>=] 400 copies/mL through Weeks 24 and 48 of study treatment).
Percentage of Participant with Treatment Adherence (95%) Based on Tablet Count up to Weeks 24 and 48
Percentage of adherent participants as measure of treatment compliance will be assessed by tablet count.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03563742
Brief Title
A Study to Determine the Safety and Efficacy of Rilpivirine in Treatment-naive Indian Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Infection
Acronym
RISE
Official Title
Open-Label Study With Rilpivirine in Treatment-naïve Indian Subjects With HIV-1 Infection to Determine Safety and Efficacy
Study Type
Interventional
2. Study Status
Record Verification Date
June 2022
Overall Recruitment Status
Terminated
Why Stopped
High SF rate (less treatment-naïve subjects & subjects with viral load <100000). Reevaluation in scientific position in India after internal discussion.
Study Start Date
September 24, 2018 (Actual)
Primary Completion Date
June 28, 2021 (Actual)
Study Completion Date
June 28, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Johnson & Johnson Pte Ltd
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The primary purpose of the study is to evaluate the efficacy of rilpivirine (RPV)-based regimen in human immunodeficiency virus type 1 (HIV-1) infected, antiretroviral (ARV) treatment-naive participants, as determined by the percentage of virologic responders defined as having HIV-1 ribonucleic acid (RNA) less than 400 copies/ milliliter (mL) at Week 24.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Human Immunodeficiency Virus Infections
Keywords
Treatment-naive, rilpivirine, India
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
58 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment: Rilpivirine+Combination Therapy (TDF/3TC)
Arm Type
Experimental
Arm Description
The participants will receive antiretroviral treatment of rilpivirine 25 milligram (mg) tablet orally once daily from Day 1 for 48 weeks with a meal to improve absorption. The participants will also receive background combination therapy of 1 tablet orally once daily containing 300 mg tenofovir disoproxil fumarate (TDF) and 300 mg lamivudine (3TC).
Intervention Type
Drug
Intervention Name(s)
Rilpivirine 25 mg
Other Intervention Name(s)
Edurant
Intervention Description
Participants will receive rilpivirine 25 mg tablet orally once daily.
Intervention Type
Drug
Intervention Name(s)
Tenofovir Disoproxil Fumarate (TDF)/Lamivudine (3TC)
Other Intervention Name(s)
Tenvir-L
Intervention Description
Participants will receive 1 fixed dose combination tablet once daily containing 300 mg TDF and 300 mg 3TC.
Primary Outcome Measure Information:
Title
Percentage of Participants who are Virologic Responders (HIV-1 RNA <400 Copies/mL) at Week 24
Description
Virologic responders are defined as participants having viral load (plasma Human Immunodeficiency Virus-Type 1 Ribonucleic Acid [HIV-1 RNA] levels) less than (<) 400 copies/milliliter (mL) at Week 24 (Food and Drug Administration [FDA]-defined snapshot analysis).
Time Frame
Week 24
Secondary Outcome Measure Information:
Title
Percentage of Participants who are Virologic Responders (HIV-1 RNA <50 Copies/mL) at Week 24
Description
Virologic responders are defined as participants having viral load (plasma HIV-1 RNA levels) <50 copies/mL at Week 24 (FDA-defined snapshot analysis).
Time Frame
Week 24
Title
Percentage of Participants who are Virologic Responders (Plasma HIV-1 RNA Levels <50, <400 and <1,000 Copies/mL) at Week 48
Description
Virologic responders are defined as participants having viral load (plasma HIV-1 RNA levels) <50, <400 and <1,000 copies/mL at Week 48 (FDA-defined snapshot analysis).
Time Frame
Week 48
Title
Absolute Value in Cluster of Differentiation 4 Positive (CD4+) T-Cell Count at Weeks 24 and 48
Description
CD4+T cell absolute counts will be determined at Weeks 24 and 48.
Time Frame
At Weeks 24 and 48
Title
Change from Baseline in CD4+ T Cell Count at Weeks 24 and 48
Description
Change from baseline in CD4+ T cell count will be determined at Weeks 24 and 48.
Time Frame
Baseline, Weeks 24 and 48
Title
Percentage of Participants with Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Participants Experiencing Premature Discontinuation due to AEs Through Week 48
Description
Percentage of participants with Grade 3 and 4 AEs will be assessed. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Percentage of participants who prematurely discontinued study due to AEs will also be analyzed.
Time Frame
Through Week 48
Title
Percentage of Participants with Laboratory Abnormalities
Description
Percentage of participants with laboratory abnormalities will be reported.
Time Frame
Up to Week 48
Title
Number of Participant with Clinically Significant Change from Baseline in Laboratory Parameters
Description
Number of participants with clinically significant change from baseline in laboratory parameters related to hematology, serum chemistry will be assessed.
Time Frame
Baseline up to Week 48
Title
Emergence of Viral Resistance Through Weeks 24 and 48
Description
Resistance analysis will be determined using genotypic analysis at the time of virological failure (that is, 2 consecutive plasma HIV-1 RNA levels greater than or equal to [>=] 400 copies/mL through Weeks 24 and 48 of study treatment).
Time Frame
Through Weeks 24 and 48
Title
Percentage of Participant with Treatment Adherence (95%) Based on Tablet Count up to Weeks 24 and 48
Description
Percentage of adherent participants as measure of treatment compliance will be assessed by tablet count.
Time Frame
Up to Weeks 24 and 48
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Must have documented human immunodeficiency virus type 1 (HIV-1) infection
Must be antiretroviral (ARV) treatment-naïve
Have plasma HIV-1 ribonucleic acid (RNA) less than (<) 100,000 copies/milliliter (mL) at screening visit
Have cluster of CD4+ T-cell count (greater than) >200/ cubic millimeter (mm^3) at screening visit
Women of childbearing potential must have a negative serum (beta human chorionic gonadotropin [beta hCG]) pregnancy test at screening; and a negative urine (or serum, if required by local regulations) pregnancy test before the first dose of study
Exclusion Criteria:
History of any primary nucleo(t)side reverse transcriptase inhibitor (N[t]RTI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations (if testing performed locally, and results are available), as defined by the current International AIDS (acquired immunodeficiency syndrome) Society-United States (USA) (International Antiviral Society-USA) 2017 guidelines
Has clinical or laboratory evidence of significantly decreased hepatic function or decompensation, irrespective of liver enzyme levels (hepatic insufficiency)
Diagnosed with acute viral hepatitis at screening or before baseline
Infected with Mycobacterium tuberculosis which is likely to require rifampicin-based treatment during the study
Has a Grade 3 or 4 laboratory abnormality as defined by the Division of AIDS (DAIDS) for Grading the Severity of Adult and Pediatric Adverse Events criteria with the following exceptions unless clinical assessment foresees an immediate health risk to the participant: (a) Preexisting diabetes or with asymptomatic glucose Grade 3 or 4 elevations (b) Asymptomatic triglyceride or cholesterol elevations of Grade 3 or 4
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Johnson & Johnson Pte Ltd Clinical Trial
Organizational Affiliation
Johnson & Johnson Pte Ltd
Official's Role
Study Director
Facility Information:
Facility Name
St.Johns Medical College and Hospital
City
Bengaluru
ZIP/Postal Code
560034
Country
India
Facility Name
Chennai Antiviral Research and Treatment(CART) Clinical Research Site
City
Chennai
ZIP/Postal Code
600113
Country
India
Facility Name
YRGCARE
City
Chennai
ZIP/Postal Code
600113
Country
India
Facility Name
Manipal University-Kasturba Medical College
City
Mangalore
ZIP/Postal Code
575001
Country
India
Facility Name
Lata Mangeshkar Hospital
City
Nagpur
ZIP/Postal Code
440001
Country
India
Facility Name
Deenanath Mangeshkar Hospital and Research Centre
City
Pune
ZIP/Postal Code
411004
Country
India
12. IPD Sharing Statement
Links:
URL
https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217051&parentIdentifier=CR108402&attachmentIdentifier=a3a0582b-a3a9-45e7-91c8-b42f2cbb4e6d&fileName=CR108402_CSR_Synopsis.pdf&versionIdentifier=
Description
Open-Label Study with Rilpivirine in Treatment-naïve Indian Subjects With HIV-1 Infection to Determine Safety and Efficacy
Learn more about this trial
A Study to Determine the Safety and Efficacy of Rilpivirine in Treatment-naive Indian Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Infection
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