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 (ELICIT)

  • STATUS
    Recruiting
  • End date
    Jun 21, 2024
  • participants needed
    180
  • sponsor
    National Institute of Allergy and Infectious Diseases (NIAID)
Updated on 10 October 2022
hysterectomy
immunodeficiency
antiretroviral
antiretroviral therapy
hiv test
atazanavir
immune globulin
antibody test
hiv-1 rna measurement

Summary

This is 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 are on antiretroviral therapy (ART)-mediated suppression. Participants will be randomly assigned to receive either letermovir once daily or no anti-CMV treatment, for 48 weeks.

Description

This is 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 will be randomized 1:1 to receive either letermovir or no anti-CMV treatment. A futility analysis will be performed after the first 40 participants to initiate study treatment reach their 8-week study visit. Study enrollment will be paused after the 40th participant starts treatment until the results of the futility analysis have been considered.

Details
Condition HIV Infections, Cytomegalovirus, CMV
Treatment Letermovir 240 MG Oral Tablet, Letermovir 480 MG Oral Tablet, Combination ART
Clinical Study IdentifierNCT04840199
SponsorNational Institute of Allergy and Infectious Diseases (NIAID)
Last Modified on10 October 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

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
NOTE: Single determinations that are between the assay quantification limit and
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
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
Persons age greater than or equal to 40 years
Ability and willingness of individual or legal guardian/representative to provide
informed consent

Exclusion Criteria

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
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
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