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HIV/AIDSPhase 2ReNewNCT03549689

Effect of Reducing Nucleotide Exposure on Bone Health (ReNew)

A Phase 2 study testing Dolutegravir (DTG) 50MG/lamivudine (3TC) 300MG FIXED DOSE COMBINATION (FDC) and Current tenofovir alafenamide (TAF)-containing ART regimen in people with HIV/AIDS and HIV-1-infection, run by Philip Grant at 10 sites in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This is an open-label, randomized pilot study to assess the effect on bone mineral density (BMD) of a switch from a tenofovir alafenamide-containing antiretroviral regimen to dolutegravir/lamivudine vs. a continuation of the tenofovir alafenamide-containing regimen. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
HIV/AIDS, HIV-1-infection, Osteopenia
What is being tested?
Dolutegravir (DTG) 50MG/lamivudine (3TC) 300MG FIXED DOSE COMBINATION (FDC) and Current tenofovir alafenamide (TAF)-containing ART regimen
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
10 sitesUnited States
Study dates
1 Aug 2019to 1 Jul 2021
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • HIV-1 infection, as documented by a positive 4th generation assay or by any licensed ELISA test kit confirmed by Western blot at any time prior to study entry.
  • Age ≥18 years
  • HIV-1 RNA BLQ (e.g., <20 copies/mL or other threshold based on the local viral load assay used) for at least 12 months prior to study entry excluding blips (i.e., a single measurement <200 copies/mL preceded and followed by measurements BLQ)
  • On a stable TAF-containing ART that also includes at least 2 other antiretrovirals, with no changes in the 12 months prior to entry (except for a switch to a co-formulated tablet from the component tablets or a switch from ritonavir to cobicistat)
  • Lumbar spine, femoral neck or total hip BMD T-score ≤-1.0 from a DXA scan within the past 48 weeks
  • If receiving testosterone or estrogen replacement therapy, on a stable dose for ≥3 months prior to enrollment without plan to change dose during the study period.
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  • Acceptable blood laboratory values at screening visit:
  • CD4+ T-cell count ≥200 cells/µL
  • Phosphate ≥2mg/dL
  • 25-hydroxyvitamin D level ≥10 ng/ml
  • Calculated creatinine clearance (CrCl) ≥50 mL/min as estimated by the Cockcroft-Gault equation*:
  • For men = CrCl (mL/min) = (140 - age in years) x (body weight in kg) ÷ (serum creatinine in mg/dL x 72)
  • For women, multiply the above result by 0.85
  • For women of reproductive potential, negative serum or urine pregnancy test prior to screening and a negative urine pregnancy test at the entry visit prior to randomization and agreeable to using a contraceptive of choice during the study period.
  • "Women of reproductive potential" are defined as women who have not been post-menopausal for at least 24 consecutive months (i.e., who have had menses within the preceding 24 months) and have not undergone surgical sterilization (i.e., hysterectomy, bilateral oophorectomy, or tubal ligation; participant report sufficient)

Who cannot join

  • Current systemic glucocorticoid use
  • Lumbar spine, femoral neck or total hip BMD T-score <-3.0
  • Previous, current pharmacologic treatment, or plan for initiation of therapy for osteoporosis (i.e., bisphosphonates, teriparatide, denosumab, tamoxifen or raloxifene)
  • Previous fragility fracture (i.e., any fall from a standing height or less that resulted in a fracture)
  • History of genotypic resistance or phenotypic resistance to either DTG or 3TC. The interpretation of genotypic resistance is based on output from the Stanford HIV Resistance Database (available at https://hivdb.stanford.edu). Isolates with an interpretation of low-level resistance or higher are considered resistant.
  • History of virologic failure (i.e., confirmed HIV-1 RNA level ≥200 copies/mL after over 6 months of therapy) while on an integrase inhibitor (i.e., raltegravir, elvitegravir, bictegravir, or dolutegravir) or on lamivudine/emtricitabine prior to study enrollment. Any antiretroviral history (even before routine virologic monitoring became standard of care) that would suggest the presence of the M184V mutation should be considered exclusionary
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  • ALT ≥5 X ULN, OR ALT ≥3xULN and bilirubin ≥1.5xULN (with >35% direct bilirubin)
  • Severe hepatic impairment (Child Pugh Class C)
  • Anticipated need for antiviral therapy for HCV
  • Hepatitis B surface antigen positive or Hepatitis B DNA positive
  • Weight >300 pounds, precluding safe DXA testing
  • Breastfeeding, pregnancy, or plans to become pregnant during the study
  • Known allergy/sensitivity to DTG or 3TC.
  • Receipt or planned receipt of prohibited concomitant medications (See section 5.4)
  • Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study procedures and treatment.
  • Any serious medical or psychiatric illness that, in the opinion of the site investigator, precludes safe participation or adherence to study procedures.

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

United States10 sites

  • Emory

    Atlanta, Georgia, 75440

  • University of Colorado

    Aurora, Colorado, 80045

  • Johns Hopkins

    Baltimore, Maryland, 21287

  • University of Alabama Birmingham

    Birmingham, Alabama, 35233

  • Northwestern

    Chicago, Illinois, 60611

  • Dallas VA Medical Center

    Dallas, Texas, 75216

  • UT Houston

    Houston, Texas, 77030

  • Columbia

    New York, New York, 10032

  • Stanford University

    Palo Alto, California, 94305

  • Penn

    Philadelphia, Pennsylvania, 19104

Other trials in United States

About this study

This is an open-label, randomized pilot study to assess the effect on bone mineral density (BMD) of a switch from a tenofovir alafenamide-containing antiretroviral regimen to dolutegravir/lamivudine vs. a continuation of the tenofovir alafenamide-containing regimen.

Being tested
Dolutegravir (DTG) 50MG/lamivudine (3TC) 300MG FIXED DOSE COMBINATION (FDC), Current tenofovir alafenamide (TAF)-containing ART regimen
Medical subject headings
Acquired Immunodeficiency Syndrome, Bone Diseases, Metabolic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Dolutegravir (DTG) 50MG/lamivudine (3TC) 300MG FIXED DOSE COMBINATION (FDC)Drug

    Participants randomized to the Switch Arm will take DTG 50mg/3TC 300mg FDC once daily with or without food at approximately the same time each day.

  • Current tenofovir alafenamide (TAF)-containing ART regimenDrug

    Continuation of current TAF-containing ART for 96 weeks.

Study groups in NCT03549689
Study groupRoleWhat they receive
SwitchExperimentalDolutegravir (DTG) 50MG/ lamivuidne (3TC) 300MG FIXED_DOSE COMBINATION (FDC) DAILY at randomization for 96 weeks
Receives: Drug: Dolutegravir (DTG) 50MG/lamivudine (3TC) 300MG FIXED DOSE COMBINATION (FDC)
ContinuationActive comparatorContinue current tenofovir alafenamide (TAF)-containing ART regimen from weeks 0 to 96.
Receives: Drug: Current tenofovir alafenamide (TAF)-containing ART regimen

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percent change in lumbar spine Bone Mineral Density (BMD) at 96 weeks

    Compare the percentage change from entry to 96 weeks in lumbar spine BMD in those randomized to DTG/3TC vs. those continuing a TAF-based regimen

    Measured: Baseline and 96 weeks

Secondary outcomes (17)

  1. Percentage change in lumbar spine BMD at 48 weeks

    Compare the percentage change from entry to 48 weeks in lumbar spine BMD in those randomized to DTG/3TC vs. those continuing a TAF-based regimen

    Measured: Baseline and 48 weeks

  2. Percentage change in total hip BMD at 48 weeks

    Compare the percentage change from entry to 48 weeks in total hip BMD in those randomized to DTG/3TC vs. those continuing a TAF-based regimen

    Measured: Baseline, 48 weeks

  3. Percentage change in total hip BMD at 96 weeks

    Compare the percentage change from entry to 96 weeks in total hip BMD in those randomized to DTG/3TC vs. those continuing a TAF-based regimen

    Measured: Baseline, 96 weeks

  4. Change in CTX (a bone resorption marker)

    Compare the changes in CTX from entry to 12, 48, and 96 weeks

    Measured: Baseline, 12 weeks, 48 weeks, and 96 weeks

  5. Change in P1NP (a bone deposition marker)

    Compare the changes in P1NP from entry to 12, 48, and 96 weeks

    Measured: Baseline, 12 weeks, 48 weeks, and 96 weeks

  6. Change in urine β2-microglobulin (renal tubular marker)

    Compare the changes in urine β2-microglobulin from entry to 48 weeks and 96 weeks.

    Measured: Baseline, 48 weeks, and 96 weeks

  7. Change in urine RBP (renal tubular marker)

    Compare the changes in RBP from entry to 48 weeks and 96 weeks.

    Measured: Baseline, 48 weeks, and 96 weeks

  8. Change in urine protein

    Compare the changes in protein from entry to 48 weeks and 96 weeks.

    Measured: Baseline, 48 weeks, and 96 weeks

  9. Change in urine albumin

    Compare the changes in urine albumin from entry to 48 weeks and 96 weeks.

    Measured: Baseline, 48 weeks, and 96 weeks

  10. Change in fractional excretion in phosphate

    Compare the changes in fractional excretion of phosphate from entry to 48 weeks and 96 weeks.

    Measured: Baseline, 48 weeks, and 96 weeks

  11. Percentage change in total lean mass

    Compare the percentage change from entry to 48 weeks and 96 weeks in total lean mass (as measured by whole body DXA)

    Measured: Baseline, 48 weeks, and 96 weeks

  12. Percentage change in trunk fat

    Compare the percentage change from entry to 48 weeks and 96 weeks in trunk fat (as measured by whole body DXA)

    Measured: Baseline, 48 weeks, and 96 weeks

  13. Percentage change in limb fat

    Compare the percentage change from entry to 48 weeks and 96 weeks in limb fat (as measured by DXA)

    Measured: Baseline, 48 weeks, and 96 weeks

  14. Maintenance of HIV RNA level

    Compare the levels of HIV RNA <50 copies/mL and below the limit of quantification (BLQ) at 48 weeks and 96 weeks using the FDA snapshot algorithm

    Measured: 48 weeks and 96 weeks

  15. Grade 3 or 4 adverse events

    Compare rates of grade 3 or 4 adverse events experienced by participants through 96 weeks

    Measured: 96 weeks

  16. Treatment discontinuation of study medication due to adverse effect

    Compare treatment discontinuation of study medication due to adverse effect experienced by participants through 96 weeks

    Measured: 96 weeks

  17. Change in fasting lipids

    Compare changes in fasting lipids (total cholesterol, LDL, HDL, and triglycerides) at entry, 48 weeks, and 96 weeks

    Measured: Entry, 48 weeks, and 96 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Jun 2018
  2. Study start1 Aug 2019 (estimated)
  3. Primary completion1 Jul 2021 (estimated)
  4. Study completion1 Jul 2021 (estimated)

Why it stopped: Withdrawn by drug manufacturer

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03549689
Sponsor's protocol ID
43453
Acronym
ReNew
Status last verified
Mar 2021
First submitted
26 Apr 2018
Last updated
15 Mar 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Dolutegravir (DTG) 50MG/lamivudine (3TC) 300MG FIXED DOSE COMBINATION (FDC) and Current tenofovir alafenamide (TAF)-containing ART regimen in people with HIV/AIDS and HIV-1-infection, run by Philip Grant at 10 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 15 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent change in lumbar spine Bone Mineral Density (BMD) at 96 weeks (time frame: Baseline and 96 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03549689.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2021.

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