Ignite Creation Date:
2025-12-25 @ 12:10 AM
Ignite Modification Date:
2026-04-21 @ 12:06 PM
Study NCT ID:
NCT05220358
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-08-03
First Post:
2022-01-31
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Changes in Immunologic Parameters Following the Addition of Fostemsavir in Virologically Suppressed Immunologic Non-responders Living With HIV-the RECOVER Study
Sponsor:
Orlando Immunology Center
Organization:
Study Overview
Official Title:
Changes in Immunologic Parameters Following the Addition of Fostemsavir in Virologically Suppressed Immunologic Non-responders Living With HIV-the RECOVER Study
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The RECOVER study is a self-controlled case series to evaluate whether the addition of Fostemsavir (Rukobia) to a stable HIV regimen in virologically suppressed patients living with HIV who never experience optimal CD4 T-cell count recovery can result in meaningful increases in different immunologic parameters such as CD4 T-cell count, CD4 T-cell percentage and CD4/CD8 ratio
Detailed Description:
In July 2020 the FDA approved fostemsavir (FTR), a prodrug of its active moiety temsavir which is a first-in class attachment inhibitor to be used in combination with other antiretrovirals (ARVs) to treat HIV infection in patients with multi-class drug resistance who are failing their current ARV regimen \[1\]. FTR is well-tolerated, dosed orally twice-daily, has no food requirement, no need for renal or hepatic dose adjustment and few drug-drug interactions (DDIs) \[1-3\]. FDA approval was based on 96-week data from the BRIGHTE study which demonstrated that addition of FTR to an optimized background regimen (OBR) among patients with multi-drug resistance failing their current regimen resulted in 96-week virologic suppression rates of 60% among patients with 1-2 fully active ARV classes remaining at baseline (randomized cohort) and 37% among patients with 0 fully active ARV classes remaining at baseline (non-randomized cohort) \[4\]. Robust CD4+ T-cell recovery was observed with a mean increase of 90 and 205 cells/mm3 through Weeks 24 and 96 respectively among patients in the randomized cohort \[4\]. The gain in CD4+ T-cells was however most impressive among the most immunocompromised patients, at Week 96 a mean increase of 240 cells/mm3 was observed among those with baseline CD4+ T-cell counts \<20 cells/mm3 and 56% of patients with baseline CD4+ T-cell counts \<50 cells/mm3 had achieved a CD4+ T-cell count of ≥200 cells/mm3 \[4\].
These data have raised questions about whether FTR has the ability to promote CD4+ T-cell recovery independently of HIV viral suppression. This first-in-class attachment inhibitor has a unique mechanism of action, the active moiety temsavir binds directly to viral gp120 preventing HIV-1 from interacting with the host immune cell. This process leaves the CD4+ T-cell untouched and it is hypothesized that temsavir binding to gp120 inhibits gp120-mediated apoptosis of CD4+ T-cells and does not allow for activation of other downstream inflammatory pathways that may contribute to CD4+ T-cell death \[2\]. Other clinical trials of ARVs used in heavily-treatment experienced populations, including those with ibalizumab, dolutegravir, enfuvirtide, maraviroc and etravirine have not demonstrated the degree of CD4+ T-cell recovery observed in the BRIGHTE study \[5-9\]. Cumulatively these data suggest that FOS may be of benefit in individuals who experience suboptimal immunologic recovery despite achieving viral suppression also known as immunologic non-responders (INRs).
Since 1997, researchers have struggled to identify agents that can restore CD4+T-cell counts and reduce immune activation and inflammation in virologically suppressed INRs \[10\]. Despite achieving ARV efficacy, this group continues to be at higher risk of disease progression to AIDS, complications related to opportunistic infections (OIs) and death \[10, 11\]. Recently, data has also revealed that persistent immune activation and inflammation also contributes to higher rates of non-AIDS related events such as hypertension, hyperlipidemia, hyperglycemia and cardiovascular disease \[11\]. Multiple strategies to address CD4+ T-cell depletion and persistent immune activation among INRs have been investigated over the years, these include the use of adjunctive maraviroc, immune modulators, statins, sitagliptin, niacin, antivirals, nutritional supplements and growth hormone in combination with ART \[10, 12-14\]. Unfortunately, none of these has demonstrated consistent efficacy and some studies have even revealed loss of virologic control and the occurrence of serious adverse events (AEs) when adjunct therapies were used \[10\]. These findings highlight an urgent need to identify novel options as adjunct therapy for CD4+T-cell recovery and to reduce inflammation and immune activation among INRs. An ideal agent for this purpose would be well-tolerated, have few DDIs with ARVs and have a low risk of contributing to virologic failure when combined with ARVs. Based on data from the BRIGHTE study, we hypothesize that FTR would be efficacious at establishing significant immune reconstitution in INRs without compromising virologic efficacy or patient safety.
Here, we propose a self-controlled case series to evaluate the change in immunologic parameters following the addition of FTR to baseline ARV regimens among virologically suppressed INRs through 48 weeks of treatment.
These data have raised questions about whether FTR has the ability to promote CD4+ T-cell recovery independently of HIV viral suppression. This first-in-class attachment inhibitor has a unique mechanism of action, the active moiety temsavir binds directly to viral gp120 preventing HIV-1 from interacting with the host immune cell. This process leaves the CD4+ T-cell untouched and it is hypothesized that temsavir binding to gp120 inhibits gp120-mediated apoptosis of CD4+ T-cells and does not allow for activation of other downstream inflammatory pathways that may contribute to CD4+ T-cell death \[2\]. Other clinical trials of ARVs used in heavily-treatment experienced populations, including those with ibalizumab, dolutegravir, enfuvirtide, maraviroc and etravirine have not demonstrated the degree of CD4+ T-cell recovery observed in the BRIGHTE study \[5-9\]. Cumulatively these data suggest that FOS may be of benefit in individuals who experience suboptimal immunologic recovery despite achieving viral suppression also known as immunologic non-responders (INRs).
Since 1997, researchers have struggled to identify agents that can restore CD4+T-cell counts and reduce immune activation and inflammation in virologically suppressed INRs \[10\]. Despite achieving ARV efficacy, this group continues to be at higher risk of disease progression to AIDS, complications related to opportunistic infections (OIs) and death \[10, 11\]. Recently, data has also revealed that persistent immune activation and inflammation also contributes to higher rates of non-AIDS related events such as hypertension, hyperlipidemia, hyperglycemia and cardiovascular disease \[11\]. Multiple strategies to address CD4+ T-cell depletion and persistent immune activation among INRs have been investigated over the years, these include the use of adjunctive maraviroc, immune modulators, statins, sitagliptin, niacin, antivirals, nutritional supplements and growth hormone in combination with ART \[10, 12-14\]. Unfortunately, none of these has demonstrated consistent efficacy and some studies have even revealed loss of virologic control and the occurrence of serious adverse events (AEs) when adjunct therapies were used \[10\]. These findings highlight an urgent need to identify novel options as adjunct therapy for CD4+T-cell recovery and to reduce inflammation and immune activation among INRs. An ideal agent for this purpose would be well-tolerated, have few DDIs with ARVs and have a low risk of contributing to virologic failure when combined with ARVs. Based on data from the BRIGHTE study, we hypothesize that FTR would be efficacious at establishing significant immune reconstitution in INRs without compromising virologic efficacy or patient safety.
Here, we propose a self-controlled case series to evaluate the change in immunologic parameters following the addition of FTR to baseline ARV regimens among virologically suppressed INRs through 48 weeks of treatment.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?: