HIV and cytomegalovirus viral load and clinical outcomes in AIDS and cytomegalovirus retinitis patients: Monoclonal Antibody Cytomegalovirus Retinitis Trial

Jabs, Douglas A.; Gilpin, Adele M. K.; Min, Yuan‐I; Erice, Alejo; Kempen, John H.; Quinn, Thomas C.

doi:10.1097/00002030-200204120-00007

Cited by 36 publications

(21 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous investigations of monoclonal antibodies targeting CMV have included MSL-109 (e.g., sevirumab), a monoclonal antibody that neutralizes CMV entry by binding to gH. In clinical trials, MSL-109 did not demonstrate improved outcomes in the treatment of CMV retinitis in AIDS patients and prevention of CMV infection after hematopoietic stem cell transplantation (51)(52)(53)(54)(55). As opposed to MSL-109, RG7667 targets two distinct antigens on the viral surface in a single therapy and is a novel approach to the prevention of CMV infection.…”

Section: Discussionmentioning

confidence: 99%

Phase 1 Randomized, Double-Blind, Placebo-Controlled Study of RG7667, an Anticytomegalovirus Combination Monoclonal Antibody Therapy, in Healthy Adults

Ishida

Burgess²,

Derby³

et al. 2015

Antimicrob Agents Chemother

View full text Add to dashboard Cite

dCytomegalovirus can cause debilitating and life-threatening disease in newborns infected in utero and immunocompromised individuals, including transplant recipients. RG7667 is a unique combination of two monoclonal antibodies that binds glycoprotein complexes on the surface of cytomegalovirus and inhibits its entry into host cells. A phase 1 first-in-human, randomized, double-blind, placebo-controlled, dose-escalation study of RG7667 given intravenously was conducted in 181 healthy adults. The study involved a single ascending dose stage (1, 3, 5, and 10 mg/kg each antibody; n ‫؍‬ 21), a multiple ascending dose stage (5 and 10 mg/kg each antibody monthly for 3 doses; n ‫؍‬ 10), and a multiple dose expansion stage (10 mg/kg each antibody monthly for 3 doses; n ‫؍‬ 150). Subjects were followed for 85 to 141 days to evaluate safety, tolerability, pharmacokinetics, and immunogenicity. Most adverse events were mild, and the incidence of adverse events was similar among the RG7667 and placebo groups. RG7667 had dose-proportional pharmacokinetics in all three dosing stages, a mean terminal half-life of 20 to 30 days, and an overall pharmacokinetic profile consistent with that of a human monoclonal antibody that lacks endogenous host targets. The proportion of subjects developing an antitherapeutic antibody response was not higher in the RG7667 group than in the placebo group. In summary, single and multiple doses of RG7667 were found to be safe and well-tolerated in healthy adults and had a favorable pharmacokinetic and immunogenicity profile. This study supports further development of RG7667 as a therapy for the prevention and treatment of cytomegalovirus infection in susceptible populations. (This study has been registered at ClinicalTrials.gov under registration no. NCT01496755.)

show abstract

Section: Discussionmentioning

confidence: 99%

Phase 1 Randomized, Double-Blind, Placebo-Controlled Study of RG7667, an Anticytomegalovirus Combination Monoclonal Antibody Therapy, in Healthy Adults

Ishida

Burgess²,

Derby³

et al. 2015

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…Thus, in the pre-HAART era, CMV DNA blood testing had insufficient clinical utility for use in monitoring the development of CMV disease. There was also evidence from 1 large, multicenter CMVR-treatment study that measurement of neither CMV DNA nor CMV pp65 antigen in blood was predictive of subsequent progression of retinitis [34].…”

Section: Discussionmentioning

confidence: 99%

Results of a Cytomegalovirus (CMV)–Specific CD8⁺/Interferon‐γ⁺Cytokine Flow Cytometry Assay Correlate with Clinical Evidence of Protective Immunity in Patients with AIDS with CMV Retinitis

et al. 2004

View full text Add to dashboard Cite

To evaluate the potential clinical utility of a cytomegalovirus (CMV)-specific CD8+/interferon (IFN)- gamma+ cytokine flow cytometry (CFC) assay for patients with CMV retinitis (CMVR), stored peripheral blood mononuclear cell specimens were obtained from patients with active CMVR (i.e., having clinical evidence of absent CMV-protective immunity), as well as from highly active antiretroviral therapy-treated patients with CMVR who were able to discontinue anti-CMV therapy without subsequent progression of retinitis (i.e., having clinical evidence of restored CMV-protective immunity). Positive CD8+/IFN- gamma+ T lymphocyte responses to CMV phosphoprotein 65 or immediate early peptide-pool stimulation were present in specimens from only 3 of 10 patients with active CMVR but were present in at least 1 specimen from all 20 patients with immunorestored CMVR, with a mean of 2.4 specimens/patient tested, spanning up to 6 months of observation (P = .0001). Among the patients with immunorestored CMVR, positive responses were present in all longitudinal specimens from 15 of the 20 patients. These data suggest that further testing of the CMV-specific CD8+/IFN- gamma+ CFC assay, for clinical utility in predicting incident and progressive CMVR disease, is warranted.

show abstract

“…During the following years, these findings have been confirmed in larger cohorts and by evaluating different clinical specimens. Detection of CMV-DNA in plasma (Jabs et al, 2002) or whole blood (Bowen et al, 1997) at the time of initial diagnosis of retinitis was associated with a higher risk of mortality than was a high HIV viral load. Similarly, asymptomatic patients with CMV-DNA detectable in plasma at the beginning of HAART had a significantly increased risk of developing CMV endorgan disease subsequently (Nokta et al, 2002).…”

Section: Detection Of CMV In Clinical Specimen and Its Clinical Signimentioning

confidence: 94%

Cytomegalovirus disease in the era of highly active antiretroviral therapy (HAART)

Steininger

Puchhammer‐Stöckl

Popow‐Kraupp

2006

Journal of Clinical Virology

View full text Add to dashboard Cite

HIV and cytomegalovirus viral load and clinical outcomes in AIDS and cytomegalovirus retinitis patients: Monoclonal Antibody Cytomegalovirus Retinitis Trial

Cited by 36 publications

References 32 publications

Phase 1 Randomized, Double-Blind, Placebo-Controlled Study of RG7667, an Anticytomegalovirus Combination Monoclonal Antibody Therapy, in Healthy Adults

Phase 1 Randomized, Double-Blind, Placebo-Controlled Study of RG7667, an Anticytomegalovirus Combination Monoclonal Antibody Therapy, in Healthy Adults

Results of a Cytomegalovirus (CMV)–Specific CD8⁺/Interferon‐γ⁺Cytokine Flow Cytometry Assay Correlate with Clinical Evidence of Protective Immunity in Patients with AIDS with CMV Retinitis

Cytomegalovirus disease in the era of highly active antiretroviral therapy (HAART)

Contact Info

Product

Resources

About

HIV and cytomegalovirus viral load and clinical outcomes in AIDS and cytomegalovirus retinitis patients: Monoclonal Antibody Cytomegalovirus Retinitis Trial

Cited by 36 publications

References 32 publications

Phase 1 Randomized, Double-Blind, Placebo-Controlled Study of RG7667, an Anticytomegalovirus Combination Monoclonal Antibody Therapy, in Healthy Adults

Phase 1 Randomized, Double-Blind, Placebo-Controlled Study of RG7667, an Anticytomegalovirus Combination Monoclonal Antibody Therapy, in Healthy Adults

Results of a Cytomegalovirus (CMV)–Specific CD8+/Interferon‐γ+Cytokine Flow Cytometry Assay Correlate with Clinical Evidence of Protective Immunity in Patients with AIDS with CMV Retinitis

Cytomegalovirus disease in the era of highly active antiretroviral therapy (HAART)

Contact Info

Product

Resources

About

Results of a Cytomegalovirus (CMV)–Specific CD8⁺/Interferon‐γ⁺Cytokine Flow Cytometry Assay Correlate with Clinical Evidence of Protective Immunity in Patients with AIDS with CMV Retinitis