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

NCT02478632 | Completed Phase 3 Results

• 1 other identifier: 202094
• Study Type: interventional
• Target: 102
• Locations: 6 countries
• Sites: 32

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.

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

Outcome Measures

Primary Outcomes (1)

• Percent Change From Baseline in Total Hip Bone Mineral Density (BMD) at 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.

  Baseline (Day 1) and Week 48

Secondary Outcomes (12)

• 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

Study Arms (2)

CAR

ACTIVE COMPARATOR

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).

Drug: Subjects do not receive study medication in this study 202094

DTG 50 mg + RPV 25 mg

EXPERIMENTAL

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)

Drug: Subjects do not receive study medication in this study 202094

Interventions

Subjects do not receive study medication in this study 202094 DRUG

Participants do not receive study medication in this study 202094.

CAR; DTG 50 mg + RPV 25 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• ViiV Healthcare: lead
• Janssen Pharmaceuticals: collaborator
• GlaxoSmithKline: collaborator

Study Sites (32)

GSK Investigational Site

Los Angeles, California, 90036, United States

Location

GSK Investigational Site

San Francisco, California, 94109, United States

Location

GSK Investigational Site

Washington D.C., District of Columbia, 20007, United States

Location

GSK Investigational Site

West Palm Beach, Florida, 33401, United States

Location

GSK Investigational Site

St Louis, Missouri, 63108, United States

Location

GSK Investigational Site

Omaha, Nebraska, 68198, United States

Location

GSK Investigational Site

Lynchburg, Virginia, 24501, United States

Location

GSK Investigational Site

Ciudad Autonoma de Buenos Aires, Buenos Aires, C1425AWK, Argentina

Location

GSK Investigational Site

Ciudad de Buenos Aires, Buenos Aires, C1202ABB, Argentina

Location

GSK Investigational Site

Rosario, Santa Fe Province, 2000, Argentina

Location

GSK Investigational Site

Buenos Aires, 1141, Argentina

Location

GSK Investigational Site

Brussels, 1000, Belgium

Location

GSK Investigational Site

Ghent, 9000, Belgium

Location

GSK Investigational Site

Liège, 4000, Belgium

Location

GSK Investigational Site

Vancouver, British Columbia, V6Z 2T1, Canada

Location

GSK Investigational Site

Toronto, Ontario, M5G 2N2, Canada

Location

GSK Investigational Site

Montreal, Quebec, H3A 1T1, Canada

Location

GSK Investigational Site

Québec, G1V 4G2, Canada

Location

GSK Investigational Site

Alicante, 03010, Spain

Location

GSK Investigational Site

Badalona, 08916, Spain

Location

GSK Investigational Site

Barcelona, 08035, Spain

Location

GSK Investigational Site

Barcelona, 08907, Spain

Location

GSK Investigational Site

Cartagena (Murcia), 30202, Spain

Location

GSK Investigational Site

Madrid, 28040, Spain

Location

GSK Investigational Site

Madrid, 28041, Spain

Location

GSK Investigational Site

Madrid, 28046, Spain

Location

GSK Investigational Site

Málaga, 29010, Spain

Location

GSK Investigational Site

Murcia, 30003, Spain

Location

GSK Investigational Site

Palma de Mallorca, 07198, Spain

Location

GSK Investigational Site

Seville, 41013, Spain

Location

GSK Investigational Site

London, E1 1BB, United Kingdom

Location

GSK Investigational Site

London, NW3 2QG, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 29239893 BACKGROUND

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: ViiV Healthcare

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  ViiV Healthcare

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2015
• First Posted: June 23, 2015
• Study Start: June 12, 2015
• Primary Completion: September 16, 2016
• Study Completion: August 17, 2018
• Last Updated: October 19, 2020
• Results First Posted: October 20, 2017

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

BE (3); US (7); ES (12); AR (4); GB (2); CA (4)