Clinical trial NCT02478632: Bone Mineral Density in Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Adult Subjects Switching From a Tenofovir Regimen to a Dolutegravir Plus Rilpivirine Regimen
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
Keywords: tenofovir disoproxil fumarate
dolutegravir plus rilpivirine
two-drug regimen
bone mineral density
dual energy X-ray absorptiometry (DEXA)
Human Immunodeficiency Virus-1
nucleoside reverse transcriptase inhibitor -sparing regimen
integrase inhibitor
Lead sponsor: ViiV Healthcare
Sponsor class: INDUSTRY
Collaborators: name: Janssen Pharmaceuticals
name: GlaxoSmithKline
First posted: 2015-06-23
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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)

Primary outcomes:
measure: Percent Change From Baseline in Total Hip Bone Mineral Density (BMD) at Week 48
timeFrame: Baseline (Day 1) and Week 48
Secondary outcomes:
measure: Percent Change From Baseline in Lumbar Spine BMD at Week 48
timeFrame: Baseline (Day 1) and Week 48
measure: Percent Change From Baseline in Total Hip and Lumbar Spine BMD-DTG+RPV Early Switch Group Through Early and Late Switch Phase
timeFrame: Baseline (Day 1), Week 48, Week 100 and Week 148
measure: 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
timeFrame: LS Baseline (Week 48), Week 100 and Week 148
measure: Change From Baseline in Total Hip and Lumbar Spine BMD at Week 48 Assessed by T-score and Z-score
timeFrame: Baseline (Day 1) and Week 48
measure: 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
timeFrame: Baseline (Day 1), Week 48, Week 100 and Week 148
measure: 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
timeFrame: LS Baseline (Week 48), Week 100, Week 148
measure: Percent Change From Baseline in Total Hip and Lumbar Spine BMD at Week 48 by Baseline Third Agent
timeFrame: Baseline (Day 1) and Week 48
measure: Change From Baseline in Total Hip and Lumbar Spine BMD T-scores and Z-scores at Week 48 by Baseline Third Agent
timeFrame: Baseline (Day 1) and Week 48
measure: 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
timeFrame: Baseline (Day 1), Week 48, Week 100 and Week 148
measure: 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
timeFrame: Baseline (Day 1), Week 48, Week 100 and Week 148
measure: 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
timeFrame: LS Baseline (Week 48), Week 100 and Week 148
measure: 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
timeFrame: LS Baseline (Week 48), Week 100 and Week 148
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: San Francisco
country: United States
facility: GSK Investigational Site
state: California
city: Washington
country: United States
facility: GSK Investigational Site
state: District of Columbia
city: West Palm Beach
country: United States
facility: GSK Investigational Site
state: Florida
city: Saint Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: Omaha
country: United States
facility: GSK Investigational Site
state: Nebraska
city: Lynchburg
country: United States
facility: GSK Investigational Site
state: Virginia
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Ciudad de Buenos Aires
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Rosario
country: Argentina
facility: GSK Investigational Site
state: Santa Fe
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Brussels
country: Belgium
facility: GSK Investigational Site
city: Gent
country: Belgium
facility: GSK Investigational Site
city: Liege
country: Belgium
facility: GSK Investigational Site
city: Vancouver
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Québec
country: Canada
facility: GSK Investigational Site
city: Alicante
country: Spain
facility: GSK Investigational Site
city: Badalona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Cartagena (Murcia)
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Murcia
country: Spain
facility: GSK Investigational Site
city: Málaga
country: Spain
facility: GSK Investigational Site
city: Palma de Mallorca
country: Spain
facility: GSK Investigational Site
city: Sevilla
country: Spain
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: ViiV Healthcare
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: McComsey GA, Lupo S, Parks D, Poggio MC, De Wet J, Kahl LP, Angelis K, Wynne B, Vandermeulen K, Gartland M, Cupo M, Aboud M; 202094 Sub-Study Investigators. Switch from tenofovir disoproxil fumarate combination to dolutegravir with rilpivirine improves parameters of bone health. AIDS. 2018 Feb 20;32(4):477-485. doi: 10.1097/QAD.0000000000001725.