KD-247, a promising HIV-neutralizing antibody

[max123]

hi, all you forum science hounds & hiv researchers.

i am interested in knowing what any of you may know about KD-247, monoclonal antibody treatment. i believe the compound first debuted in 2006 and as of 2007, is currently under investigation in human trials.

from what i've read, kd-247 has sparked interest in hiv management (immunotherapy) by showing evidence that it may neutralize hiv, reducing viral load and enhancing cd4 counts in those already infected with hiv 1, b clade, with an igpgr species neutralization sequence motif.

how common is an igpgr species neutralization sequence motif and is one's neutralization sequence motif part of standard genotyping?.

is kd 247 a temporary fix, or are its effects expected to last indefinitely from treatment?

is it safe?

i'm interested in finding out more about the compound because if it makes sound sense, is safe and will not cause any kind of drug resistance issues, i may consider joining an experimental trial, being conducted locally.

please share any info or recommendations.

thanks.

max


scientific paper on kd 247:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1472178/

clinical trial on kd 247 info:
http://clinicaltrials.gov/ct2/show/NCT00917813?term=hiv&recr=Open&state1=NA%3AUS%3AFL&rank=16


A Study of Anti-HIV Monoclonal Antibody KD-247
This study is currently recruiting participants.
ClinicalTrials.gov Identifier:    NCT00917813
  Purpose

The purpose of this study is to evaluate the safety and tolerability of 3 infusions of KD-247 over 2 weeks in HIV-1 seropositive individuals; to determine the pharmacokinetic parameters of KD-247 when administered as above; and to assess the effect of KD-247 infusions on plasma HIV-1 ribonucleic acid (RNA) load and on CD4+ T cell count

Study Type:    Interventional
Study Design:    Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Pharmacokinetics/Dynamics Study
Official Title:    A Study of the Safety, Tolerability, and Pharmacokinetics of KD-247, a Humanized Monoclonal Antibody That Recognizes the Principal Neutralizing Determinant of HIV-1, in Asymptomatic HIV-1 Seropositive Individuals Who Are Not Receiving Concurrent Antiretroviral Therapy


Further study details as provided by The Chemo-Sero-Therapeutic Research Institute:

Estimated Enrollment:    27
Study Start Date:    September 2007
Arms    Assigned Interventions
KD-247: Experimental    Drug: KD-247
Cohort 1 - 4 mg/kg KD-247 IV on Days 1, 8, and 15; Cohort 2 - 8 mg/kg KD-247 IV on Days 1, 8, and 15; Cohort 3 - 16 mg/kg KD-247 IV on Days 1, 8, and 15
Placebo: Placebo Comparator    Drug: Physiological saline
Cohort 1 - Physiological saline IV on Days 1, 8, and 15; Cohort 2 - Physiological saline IV on Days 1, 8, and 15; Cohort 3 - Physiological saline IV on Days 1, 8, and 15

Detailed Description:

A minimum of 6 active subjects and 3 placebo subjects for each dose cohort will complete 2 weeks of infusions. A maximum of 27 total subjects will be dosed with KD-247 and up to 9 total will receive placebo. Per cohort subjects randomized to active treatment will receive iv infusions of KD 247 over 2 hours at each dosing visit. Subjects randomized to placebo will receive 2-hour iv infusions of saline solution at each dosing visit. Following the first infusion of KD-247 (or placebo) for each subject in the study, there will be a 24-hour in-patient observation period before the next subject can be randomized within the study. Dose escalation will proceed only after safety data through Day 18 for all subjects in the lower-dose cohort is reviewed.

[veritas]

max123,

Here is some updated info on KD-247 (animal trials):

http://www.ncbi.nlm.nih.gov/pubmed/19528788

I believe many of your questions will be answered by the clinical trial. If you go ahead with the trial, ask those questions to those running the trial. The therapy looks promising but did you read this :

"5.Are treatment naïve or have been off antiretroviral drugs for at least 8 weeks prior to screening.
6.By genotyping, have a sequence of the portion of the HIV envelope gene encoding the principal neutralizing determinant that is consistent with neutralization by KD 247."

The above is part of the inclusion criteria for the trial.
 If you decide to go ahead with the trial, keep us informed and good luck.

v

[max123]

hi v.

thanks for the link.

it does appear that the recent animal responses to kd 247 were good, regarding cd4 preservation and negligible viral load decline. that's definitely what makes it appealing enough for to me to even provisionally consider it. however, my major concern is that there is no info that i could find published regarding potential associated adverse effects. playing devil's advocate and as we already know, hiv mutates in response to certain stimuli. one of my questions is if kd 247 could potentially induce mutation in response to its presence in the body? that's the scary part of the study, as part of the clinical trial is to test the compound's "safety." needless to say, that's the point that prompts some apprehension for me.

i'm planning to call the clin-trial contact person tomorrow to get additional info, but was curious if any forum members had any familiarity with the compound. i figured i might get more objective info outside of the sponsoring research circle...you know how that goes i did find out that the compound has in fact been studied before.

yes, i reviewed all of the criteria and think i may qualify... i'm completely treatment naive and am hiv 1, clade b infected. however, i'm unsure if i have the "sequence of the portion of the HIV envelope gene encoding the principal neutralizing determinant that is consistent with neutralization by KD 247." by that, i concluded they meant the igpgr species neutralization sequence motif (the amino acid sequence at v3). hence my asking if anyone knew if standard genotyping (which i had done last month) would contain that info. maybe the igpgr species is even the default sequence motif for the b clade itself?

well, i will update the thread after speaking with my local clin-trial rep tomorrow.

ps: i found another technical link regarding the compound that explains it's mechanisms in much greater detail: http://jvi.asm.org/cgi/content/full/81/8/3757


max

[shammah]

max, i was wondering if you ever started the study.  It looks like they are recruiting and i was thinking of doing it

[max123]

max, i was wondering if you ever started the study.  It looks like they are recruiting and i was thinking of doing it

hi shammah,

after investigating the drug, i decided against it. it turns out this drug had been investigated before and findings were that it can induce amino acid substitutions, ultimately giving rise to the potential of inducing hiv mutation. for me personally, it's just a little too risky.

max