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HIV InfectionsPhase 2ELICITNCT04840199

A Study to Evaluate the Anti-inflammatory Effects of Letermovir (Prevymis) in Adults With Human Immunodeficiency Virus (HIV)-1 and Asymptomatic Cytomegalovirus (CMV) Who Are on Suppressive Antiretroviral Therapy, Plus Its Effect on Chronic Inflammation, HIV Persistence and Other Clinical Outcomes.

A Phase 2 study testing Letermovir Oral Tablet in people with HIV Infections and Cytomegalovirus, run by National Institute of Allergy and Infectious Diseases (NIAID) at 15 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

This was an open-label, controlled study, conducted at US sites to evaluate the anti-inflammatory effectiveness of the study drug letermovir in adults with HIV and asymptomatic cytomegalovirus (CMV) who were on antiretroviral therapy (ART)-mediated suppression. Read more about this study

Who is it for?
Ages 40 years and older
Conditions the study is for
HIV Infections, Cytomegalovirus, CMV
What is being tested?
Letermovir Oral Tablet
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
44 participants
Where
15 sitesUnited States
Study dates
19 Apr 2022to 30 Nov 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

Who may be able to join

  • HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load.
  • NOTE: The term "licensed" refers to a US FDA-approved kit, which is required for all IND studies.
  • WHO (World Health Organization) and CDC (Centers for Disease Control and Prevention) guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment. More information on this criterion can be found in the protocol.
  • Currently on continuous combination ART (antiretroviral therapy) for ≥48 weeks prior to study entry. This is defined as continuous ART for the 48-week period prior to study entry with no ART interruption longer than 7 consecutive days.
  • Screening plasma HIV-1 RNA <40 copies/mL within 90 days prior to study entry using a FDA-approved assay with a quantification limit of 40 copies/mL or lower performed by any US laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent.
  • HIV-1 RNA level <40 copies/mL for at least 48 weeks prior to study entry performed by any US laboratory that has a CLIA certification or its equivalent.
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  • NOTE: Single determinations that are between the assay quantification limit and 500 copies/mL (i.e., "blips") are allowed as long as the preceding and subsequent determinations are below the level of quantification. The screening value may serve as the subsequent undetectable value following a blip.
  • CD4⁺/CD8⁺ cell count obtained within 90 days prior to study entry at any US laboratory that has a CLIA certification or its equivalent.
  • Positive CMV IgG serology, at any time prior to study entry using a FDA-approved assay at any US laboratory that has a CLIA certification or its equivalent.
  • NOTE: If a prior positive CMV IgG serology test is confirmed in the medical record, a repeat CMV IgG test is not required at screening.
  • The following laboratory values obtained within 90 days prior to study entry by any US laboratory that has a CLIA certification or its equivalent:
  • Hemoglobin >9.0 g/dL
  • Platelet count >75,000/mm³
  • Aspartate aminotransferase (AST) (SGOT), alanine aminotransferase (ALT) (SGPT), and alkaline phosphatase ≤3 x ULN (upper limit of normal)
  • Total bilirubin ≤2.5 x ULN
  • NOTE: If an individual is taking atazanavir-containing regimen at the time of screening, a total bilirubin of ≤5 x ULN is acceptable.
  • Estimated Glomerular Filtration Rate (eGFR) >30 mL/min/1.73m² or creatinine clearance (CrCl) >30 mL/min using the Cockcroft-Gault, EPI-GFR or MDRD equations located on the DMC website.
  • For individuals assigned female sex at birth and of reproductive potential, negative serum or urine pregnancy test within 24 hours prior to study entry by any US clinic or laboratory that has a CLIA certification or its equivalent, or a CLIA Certificate of Waiver for those performing a point of care (POC)/CLIA-waived test. (Urine test must have a sensitivity of <25 mlU/mL).
  • NOTE: Persons of female sex assigned at birth and of reproductive potential are defined as having reached menarche and have not been post-menopausal for at least 24 consecutive months (i.e. have had menses within the preceding 24 months), and have not undergone testosterone therapy for gender alignment or surgical sterilization such as hysterectomy, bilateral oophorectomy, tubal ligation or salpingectomy. An individual's report is considered acceptable documentation or reproductive status.
  • All participants that are participating in sexual activity that could lead to pregnancy must agree to use contraception throughout the study. At least one of the following must be used throughout the study:
  • Diaphragm or cervical cap with spermicide
  • Intrauterine device (IUD)
  • Hormone-based contraceptive
  • Condoms with or without a spermicide
  • NOTE A: Individuals who are not of reproductive potential are not required to use contraception.
  • NOTE B: Sperm-producing participants should refrain from donating sperm during the treatment period and for at least 90 days after the last dose of study treatment.
  • Ability and willingness of individual or legal guardian/representative to provide informed consent.

Who cannot join

  • Change in the ART regimen within 12 weeks prior to study entry or intended modification of ART during the study.
  • NOTE: Modifications in the dosage or frequency (i.e. twice a day [bid] to once a day [qd]) of individual antiretroviral (ARV) drugs during the 12 weeks prior to study entry are permitted. In addition, the change in formulation (e.g. from standard formulation to fixed-dose combination) is allowed within 12 weeks prior to study entry. A within class single drug substitution (e.g. switch from atazanavir to darunavir, or tenofovir disoproxil fumarate to tenofovir alafenamide) is allowed within 12 weeks prior to study entry. A switch to any other nucleoside reverse transcriptase inhibitor (NRTI) from abacavir (or vice versa) is not permissible. No other changes in ART within the 12 weeks prior to study entry are permitted.
  • Use of any of the following ARV drugs in current regimen: efavirenz, nevirapine, etravirine, lopinavir/ritonavir, and once-daily dosing of raltegravir (bid dosing of raltegravir is acceptable).
  • Two or more HIV-1 RNA determinations >200 copies/mL within 48 weeks prior to study entry.
  • Any febrile illness (>101°F) within 30 days prior to study entry.
  • Use of drugs with anti-CMV activity within 90 days prior to study entry, with the exception of standard dose valacyclovir and acyclovir. See the protocol for more information.
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  • Immunosuppressive or immunomodulatory drug use, with the exception of topical, inhaled, and intranasal corticosteroids within 90 days prior to study entry. See the protocol for more information.
  • Concomitant use of prohibited medications. See the protocol for more information.
  • Persons who are breastfeeding, pregnant or planning to become pregnant during the study.
  • Participating in a study where co-enrollment is not allowed.
  • Receipt of any vaccination within 14 days prior to study entry.
  • Presence on screening ECG or a known history of atrial tachycardia (other than sinus tachycardia). Ventricular tachycardia is also an exclusion criterion.
  • History of cardiomyopathy or congenital heart disease or evidence of advanced conduction system disease including second degree heart block Mobitz type II, third degree heart block, AV dissociation or ECG findings that may be suggestive of predisposition to arrhythmia (i.e. delta wave).
  • Known allergy/sensitivity or any hypersensitivity to components of the study drug or its formulation.
  • Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
  • Acute or serious illness requiring systemic treatment and/or hospitalization within 90 days prior to study entry.
  • Known chronic active hepatitis B virus infection within the last 24 weeks prior to study entry.
  • NOTE: Active is defined as hepatitis B surface antigen (HBsAg) positive and hepatitis B DNA (HBV DNA) positive. Persons with HBV DNA below level of quantification (BLQ) for >24 weeks prior to study entry are eligible.
  • Known chronic active hepatitis C within the last 24 weeks prior to study entry.
  • NOTE: Active is defined as a detectable plasma hepatitis C virus (HCV) RNA level. Persons with HCV RNA BLQ for >24 weeks prior to study entry are eligible.
  • Presence of history of conditions that could account for impaired neuropsychological performance (if present), including head injury with prolonged (>1 hour) loss of consciousness, central nervous system infection (e.g. encephalitis), severe learning disability, psychosis, and/or active drug or alcohol use, or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
  • History of multi-class HIV drug resistance or intolerance, such that in the opinion of the investigator, an alternative fully active antiretroviral regimen cannot be constructed should the participant experience loss of viral suppression on their current regimen during the study.

Trial locations and contacts

15 sites in 1 country.

15 sites in 1 country

United States15 sites

  • University of Colorado Hospital CRS

    Aurora, Colorado, 80045

  • Massachusetts General Hospital CRS (MGH CRS)

    Boston, Massachusetts, 02114

  • Northwestern University CRS

    Chicago, Illinois, 60611

  • Cincinnati Clinical Research Site

    Cincinnati, Ohio, 45267

  • Case Clinical Research Site

    Cleveland, Ohio, 44106

  • Vanderbilt Therapeutics (VT) CRS

    Nashville, Tennessee, 37204

  • Weill Cornell Chelsea CRS (7804)

    New York, New York, 10010

  • Weill Cornell Uptown CRS (7803)

    New York, New York, 10065

  • Penn Therapeutics, CRS

    Philadelphia, Pennsylvania, 19104

  • University of Pittsburgh CRS

    Pittsburgh, Pennsylvania, 15213

  • University of Rochester Adult HIV Therapeutic Strategies Network CRS

    Rochester, New York, 14642

  • UCSD Antiviral Research Center CRS (Site 701)

    San Diego, California, 92103

  • UCSF HIV/AIDS CRS (Site 801)

    San Francisco, California, 94110

  • University of Washington Positive Research CRS

    Seattle, Washington, 98104-9929

  • Washington University Therapeutics (WT) CRS

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: Randomized, Controlled Trial to Evaluate the Anti-inflammatory Efficacy of Letermovir (Prevymis) in Adults With Human Immunodeficiency Virus (HIV)-1 and Asymptomatic Cytomegalovirus (CMV) Who Are on Suppressive ART and Its Effect on Chronic Inflammation, HIV Persistence, and Other Clinical Outcomes

This was an open-label, controlled study, conducted at US sites to evaluate the anti-inflammatory effectiveness of the study drug letermovir in adults with HIV and asymptomatic cytomegalovirus (CMV) who were on antiretroviral therapy (ART)-mediated suppression. Participants were randomly assigned to receive either letermovir once daily or no anti-CMV treatment, for 48 weeks.

The primary hypothesis of this study was that letermovir would cause a greater reduction in plasma soluble receptor for tumor necrosis factor type II (sTNFRII) levels than no anti-CMV treatment at weeks 46/48.

Read the detailed description

This was a phase 2, randomized, open-label, controlled, multicenter trial to evaluate the anti-inflammatory efficacy of letermovir, administered once daily for 48 weeks in adults with HIV and asymptomatic CMV, who are on ART-mediated suppression. Participants were randomized 1:1 to receive either letermovir or no anti-CMV treatment. The target enrollment was 180 participants.

A futility analysis was planned to be performed after the first 40 participants to initiate study treatment reached their 8-week study visit. Study enrollment was to be paused after the 40th participant started the study until the results of the futility analysis were considered.

This study was terminated due to futility.

Being tested
Letermovir Oral Tablet
Medical subject headings
HIV Infections

What participants receive

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

  • Letermovir Oral TabletDrug

    Also called Prevymis

    480 mg administered orally once daily with or without food

Study groups in NCT04840199
Study groupRoleWhat they receive
LetermovirExperimentalParticipants randomized to letermovir for 48 weeks followed by 12 weeks off letermovir
Receives: Drug: Letermovir Oral Tablet
No anti-CMV treatmentNo interventionParticipants randomized to no study intervention for 60 weeks

What is being measured

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

  1. Change (Absolute) in sTNFRII

    The absolute change in sTNFRII from Baseline (average of study entry and treatment initiation visits) to Week 46/48 (average of Week 46 and Week 48), or the latest result in the treatment phase. Linear regression was used to estimate the mean change. The covariates were study arm and the gender and CD4 stratification factors.

    Measured: Measured at Baseline and Weeks 46 and 48

Secondary outcomes (7)

  1. Occurrence of Grade ≥3 AEs or Confirmed HIV-1 Virologic Failure

    Adverse events were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017. Adverse events were graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death.

    Confirmed virologic failure was defined as two consecutive HIV-1 RNA levels ≥200 copies/mL by real-time HIV-1 RNA testing. Participants with a plasma HIV-1 RNA ≥200 copies/mL at any visit had a confirmatory viral load obtained as soon as possible but within 14 days after the first sample was drawn, if possible. If the consecutive measurement of HIV-1 RNA was also ≥200 copies/mL, the participant was considered to have confirmed virologic failure.

    Measured: Measured from study entry through Week 48

  2. Rate of Change in Odds of Oral CMV DNA Detection

    When the number of detection outcomes was sufficient, binary repeated oral CMV DNA detection (yes/no) was modeled with generalized estimating equations (GEE) to estimate the weekly rate of change (slope). The covariates were study arm and the gender and CD4 stratification factors, as well as a three-level period effect (early treatment phase [through Week 8], late treatment phase, post-treatment phase) and its interaction with the study arm.

    Due to the small sample size and small number of detectable CMV DNA results, the GEE model was not able to provide estimates. Cross-sectional CMV DNA detection summaries have been provided instead.

    Measured: Measured at Baseline and Weeks 8, 46, 48, 52 and 60

  3. Rate of Change in Odds of Genital CMV DNA Detection

    When the number of detection outcomes was sufficient, binary repeated genital CMV DNA detection (yes/no) was modeled with generalized estimating equations (GEE) to estimate the weekly rate of change (slope). The covariates were study arm and the gender and CD4 stratification factors, as well as a three-level period effect (early treatment phase [through Week 8], late treatment phase, post-treatment phase) and its interaction with the study arm.

    The model estimates do not reflect the odds of detection, but rather, the change in the odds of detection per week on the multiplicative scale.

    Measured: Measured at Baseline and Weeks 8, 46, 48, 52 and 60

  4. Rate of Change in Odds of Rectal CMV DNA Detection

    When the number of detection outcomes was sufficient, binary repeated rectal CMV DNA detection (yes/no) was modeled with generalized estimating equations (GEE) to estimate the weekly rate of change (slope). The covariates were study arm and the gender and CD4 stratification factors, as well as a three-level period effect (early treatment phase [through Week 8], late treatment phase, post-treatment phase) and its interaction with the study arm.

    Due to the small sample size and small number of detectable CMV DNA results, the GEE model was not able to provide estimates. Cross-sectional CMV DNA detection summaries have been provided instead.

    Measured: Measured at Baseline and Weeks 8, 48 and 60

  5. Rate of Change in Odds of Plasma CMV DNA Detection

    When the number of detection outcomes was sufficient, binary repeated plasma CMV DNA detection (yes/no) was modeled with generalized estimating equations (GEE) to estimate the weekly rate of change (slope). The covariates were study arm and the gender and CD4 stratification factors, as well as a three-level period effect (early treatment phase [through Week 8], late treatment phase, post-treatment phase) and its interaction with the study arm.

    Due to the small sample size and small number of detectable CMV DNA results, the GEE model was not able to provide estimates. Cross-sectional CMV DNA detection summaries have been provided instead.

    Measured: Measured at Baseline and Weeks 8, 46, 48, 52 and 60

  6. Rate of Change in sCD163

    Repeated, continuous sCD163 was modeled with generalized estimating equations (GEE) to estimate the weekly rate of change (slope). The covariates were study arm and the gender and CD4 stratification factors, as well as a three-level period effect (early treatment phase [through Week 8], late treatment phase, post-treatment phase) and its interaction with the study arm.

    Measured: Measured at Baseline and Weeks 8, 24, 46, 48, 52 and 60

  7. Rate of Change in sTNFRII

    Repeated, continuous sTNFRII was modeled with generalized estimating equations (GEE) to estimate the weekly rate of change (slope). The covariates were study arm and the gender and CD4 stratification factors, as well as a three-level period effect (early treatment phase [through Week 8], late treatment phase, post-treatment phase) and its interaction with the study arm.

    Measured: Measured at Baseline and Weeks 8, 24, 46, 48, 52 and 60

Timeline

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

  1. First posted9 Apr 2021
  2. Study start19 Apr 2022
  3. Primary completion30 Nov 2023
  4. Study completion30 Nov 2023

Why it stopped: Permanently closed to screening and accrual due to futility

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
44 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04840199
Sponsor's protocol ID
A5383
Other IDs
38597
Acronym
ELICIT
Status last verified
Feb 2025
First submitted
7 Apr 2021
Last updated
4 Mar 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Individual participant data that underlie results in the publication, after de-identification.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Letermovir Oral Tablet in people with HIV Infections and Cytomegalovirus, run by National Institute of Allergy and Infectious Diseases (NIAID) at 15 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 27 inclusion and 22 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: stopped early, as of the sponsor's last update on 4 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 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?

Yes. Results are posted in the registry (first posted 4 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Change (Absolute) in sTNFRII (time frame: Measured at Baseline and Weeks 46 and 48). 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 NCT04840199.

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 4 Mar 2025.

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