An Evaluation of Bone Mineral Density in HIV-1-infected Adult Subjects Switching From a Tenofovir-containing Antiretroviral Therapy Regimen to a Dolutegravir Plus Rilpivirine Regimen
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 102
- 试验地点
- 1
- 主要终点
- Percent Change From Baseline in Total Hip Bone Mineral Density (BMD) at Week 48
研究概览
简要总结
The purpose of this study is to evaluate any change from baseline in bone mineral density (BMD) in subjects following the switch from a triple antiretroviral therapy (ART) regimen containing Tenofovir disoproxil fumarate (TDF) to the nucleoside reverse transcriptase inhibitor (NRTI) - sparing two - drug regimen of dolutegravir (DTG) + rilpivirine (RPV) in subjects participating in the parent studies 201636 and 201637 (SWORD-1 and SWORD-2).
This open-label, parallel group, study is a sub-study which will recruit subjects who are receiving ART regimens which include TDF at the time of randomization to receive treatment in one of two identical parent studies 201636 and 201637 (SWORD-1 and SWORD-2). These are Phase III, randomised, open-label, multicentre, parallel-group, non-inferiority studies evaluating the efficacy, safety, and tolerability of switching to DTG plus RPV from current integrase inhibitor (INI)-, non NNRTI-, or protease inhibitor (PI)-based antiretroviral regimen in HIV-1-infected adults who are virologically suppressed, having HIV-1 ribonucleic acid (RNA) levels <50 copies per millilitre (c/mL). Randomisation in the parent studies will be stratified by baseline third agent class (INI, NNRTI, or PI), age group (< or =>50 years old) and participation in this Dual energy X-ray absorptiometry (DEXA) sub-study, therefore there will also be balance across the treatment arms in this sub-study both overall and with respect to baseline third agent class and age at entry.
The study population will include approximately 75 evaluable subjects recruited from the Early Switch DTG + RPV treatment group of the parent studies 201636 and 201637, and approximately 75 evaluable subjects from the Late Switch group who continue their current antiretroviral therapy (CAR) through to Week 52 across both the 201636 and 201637 (SWORD-1 and SWORD-2) studies. Subjects participating in study 202094 will have DEXA scans performed at Day 1 and at study Weeks 48, 100 and 148 in parallel with the corresponding scheduled visits in the parent studies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Screened and eligible but not yet randomised to either of the parent studies 201636 (SWORD-1) or 201637 (SWORD-2)
- •Receiving an ART regimen which contains TDF
- •Female subjects of child bearing potential with a negative pregnancy test at both Screening and Day 1 and agrees to use one of the methods of contraception described in the protocols of the parent studies 201636 (SWORD-1) and 201637 (SWORD-2) to avoid pregnancy. Any contraception method must be used consistently, throughout the study period in accordance with the approved product label, including adherence to appropriate 'run in' periods for hormonal contraception
- •Subject is willing and able to understand the requirements of study participation and provide signed and dated written informed consent prior to Screening. Subject is considered an appropriate candidate for participation in this study
- •For subjects enrolled in France: a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category
排除标准
- •Less than three vertebra in the range of L1 to L4 that are suitable for BMD measurement by DEXA scan
- •Bilateral hip replacement
- •Uncontrolled thyroid disease: thyroid stimulating hormone (TSH) above normal range, and considered to indicate a requirement for thyroid replacement therapy
- •Male hypogonadism: serum testosterone < 300 nanogram per decilitre (ng/dL) on a sample collected before 10:00 in the morning and the subject is able and willing to start testosterone replacement therapy
- •Endocrine diseases including Cushing's syndrome and diabetes mellitus
- •History of fragility fractures
- •Ever treated for osteoporosis with bisphosphonates, oestrogen receptor modulators or other therapies, and / or severe osteoporosis as indicated by a prior DEXA scan derived T-score of -3.5 or lower value
- •Body mass index (BMI) < 18 kilogram per meter (kg/m)^2 or =>40 kg/m^2
- •Vitamin D deficiency: 25 Hydroxy Vitamin D < 15ng/mL
- •Any pre-existing physical or mental condition (including substance abuse disorder) which, in the opinion of the investigator, may interfere with the subject's ability to comply with the scheduled protocol evaluations or which may compromise the safety of the subject
- •Current use or intent to initiate, tamoxifen, bone-related treatment, e.g. biphosphonates, osteoporosis medications including selective oestrogen receptor modulator medicines (raloxifene, arzoxifene and lasofoxifene), growth hormone or anabolic steroids, except for testosterone as specified below, during the study period
- •The following are excluded unless they have been given for at least 6 months prior to Day 1, and there is no plan to stop them during the study: Anti-convulsant therapy and hormonal therapy, including female hormone replacement therapy or testosterone as a replacement therapy or supplement
- •Women who are pregnant, breastfeeding or who plan to become pregnant or breast feed during the study period
- •Subject enrolled, or anticipated to be selected to participate following study registration, in an investigational clinical protocol/s in addition to one of the parent studies 201636 or 201637 (SWORD-1 or SWORD-2)
研究组 & 干预措施
CAR
Participants do not receive study medication in this study 202094. Participants group carried over from the parent study 201636 (SWORD-1) or 201637 (SWORD-2).
干预措施: Subjects do not receive study medication in this study 202094 (Drug)
DTG 50 mg + RPV 25 mg
Participants do not receive study medication in this study 202094. Participants group carried over from the parent study 201636 (SWORD-1) or 201637 (SWORD-2)
干预措施: Subjects do not receive study medication in this study 202094 (Drug)
结局指标
主要结局
Percent Change From Baseline in Total Hip Bone Mineral Density (BMD) at Week 48
时间窗: Baseline (Day 1) and Week 48
Percent change in BMD (expressed as areal density in grams per centimeter square \[g/cm\^2\]) as specified by dual energy X-ray absorptiometry (DEXA) scans of the left 'total hip' which included the femoral neck, trochanter and inter-trochanter areas was assessed by areal density at Baseline and Week 48. The estimated value in the statistical analysis is this difference and the upper and lower limit values shown are the 95% confidence intervals. Baseline was considered as Day 1 and percent change from Baseline was calculated as Value at Week 48 minus Baseline value divided by Baseline value multiplied by 100. An analysis of covariance (ANCOVA) model was used to compare the difference. The analysis was performed on Intent-to-Treat exposed DEXA (ITT-ED) Population which comprised of all participants in the ITT-E Population who received at least one dose of study treatment, and who were registered for the 202094 study.
次要结局
- Percent Change From Baseline in Lumbar Spine BMD at Week 48(Baseline (Day 1) and Week 48)
- Percent Change From Baseline in Total Hip and Lumbar Spine BMD-DTG+RPV Early Switch Group Through Early and Late Switch Phase(Baseline (Day 1), Week 48, Week 100 and Week 148)
- Percent Change From Late Switch (LS) Baseline (Week 48) Through Week 148 in Total Hip and Lumbar Spine BMD-CAR Late Switch Group Through Late Switch Phase(LS Baseline (Week 48), Week 100 and Week 148)
- Change From Baseline in Total Hip and Lumbar Spine BMD at Week 48 Assessed by T-score and Z-score(Baseline (Day 1) and Week 48)
- Change From Baseline in Total Hip and Lumbar Spine BMD as Assessed by T-scores and Z-scores - DTG+RPV Early Switch Group Through Early and Late Switch Phase(Baseline (Day 1), Week 48, Week 100 and Week 148)
- Change From LS Baseline (Week 48) Through Week 148 in Total Hip and Lumbar Spine BMD as Assessed by T-scores and Z-scores-CAR Late Switch Group Through Late Switch Phase(LS Baseline (Week 48), Week 100, Week 148)
- Percent Change From Baseline in Total Hip and Lumbar Spine BMD at Week 48 by Baseline Third Agent(Baseline (Day 1) and Week 48)
- Change From Baseline in Total Hip and Lumbar Spine BMD T-scores and Z-scores at Week 48 by Baseline Third Agent(Baseline (Day 1) and Week 48)
- Percent Change From Baseline (Day 1) in Total Hip and Lumbar BMD by Baseline Third Agent-DTG+RPV Early Switch Group Through Early and Late Switch Phase(Baseline (Day 1), Week 48, Week 100 and Week 148)
- Change From Baseline (Day 1) in Total Hip and Lumbar Spine BMD T-scores and Z-scores by Baseline Third Agent-DTG+RPV Early Switch Group Through Early and Late Switch Phase(Baseline (Day 1), Week 48, Week 100 and Week 148)
- Percent Change From LS Baseline (Week 48) Through Week 148 in Total Hip and Lumbar Spine BMD by Baseline Third Agent-CAR Late Switch Group Through Late Switch Phase(LS Baseline (Week 48), Week 100 and Week 148)
- Change From LS Baseline (Week 48) Through Week 148 in Total Hip and Lumbar Spine BMD T-scores and Z-scores by Baseline Third Agent-CAR Late Switch Group Through Late Switch Phase(LS Baseline (Week 48), Week 100 and Week 148)