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Investigational

Monomeric DAPTA  Audio icon

Other Names: Adaptavir, Adaptavir, D-Ala1-peptide T-amide, DAPTA, Peptide T, RAP101, mDAPTA, monomeric D-Ala-peptide T-amide
Drug Class: Entry Inhibitor
Molecular Formula: C35 H56 N10 O15
Registry Number: 106362-34-9 (CAS)
Chemical Name: (D-Ala1) Peptide T Amide; DAPTA 
Chemical Class: Peptides
Company: RAPID Pharmaceuticals
Phase of Development: Phase II
Chemical Image:
Click image to enlarge
Adaptavir
Adaptavir
Molecular Weight: 856.882

(Compound details obtained from ChemIDplus Advanced,1 NIAID Therapeutics Database,2 and RAPID Pharmaceuticals press release3)
Patent Version Content

Pharmacology


Mechanism of Action: HIV-1 entry inhibitor. Monomeric DAPTA (mDAPTA) is a reformulated monomeric form of peptide T ([D-Ala1] Peptide T Amide; DAPTA), a synthetic octapeptide compound derived from the gp120 V-2 region of HIV. Peptide T is a selective CCR5 co-receptor antagonist that prevents viral entry by directly binding to the CCR5 co-receptor and subsequently inhibiting the interaction between HIV-1 gp120 and CCR5.4-7 In vitro, mDAPTA has been shown to inhibit the release of CXCR4- and CCR5-tropic HIV from CD8-depleted peripheral blood mononucleated cells (PBMCs) isolated from HIV-uninfected patients and HIV-infected patients with viral load less than 50 copies/mL.8

Half-life (T½): In a Phase I study involving participants with AIDS or AIDS-related complex (ARC), peptide T demonstrated biphasic plasma kinetics following intravenous (IV) or intranasal (IN) administration, with a first compartment half-life of 30 to 60 minutes and a second plasma clearance time of 4 to 6 hours.9

Metabolism/Elimination: In a Phase I study, participants with AIDS or ARC received peptide T via IV or IN administration. After administration, the drug could not be detected in urine.9

Resistance: In a small study of 11 HIV-infected participants receiving peptide T either alone or in combination with their current antiretroviral therapy (ART) for up to 32 weeks, no obvious CCR5 to CXCR4 co-receptor shift occurred, and treatment-resistant viruses did not emerge.10


Dosing in Clinical Trials


Peptide T
 
Study Identifiers: Not available
Phase: Not available
Study Purpose: Study to evaluate the antiviral and immunological benefits of peptide T
Study Population: Long-term HIV-infected participants with stable viral loads. Participants were either treatment-naive or treatment-experienced.
Dosing: Peptide T 2 mg administered intranasally three times a day for up to 32 weeks, given either alone or in combination with current ART.10
(See references cited above for information on study results.)

Study Identifiers: NCT00000392
Phase: II
Study Purpose: Study to determine the ability of peptide T to treat HIV-associated cognitive impairment
Study Population: HIV-infected adults with cognitive impairment and not receiving ART within 4 weeks of study entry or receiving stable ART for at least 12 weeks prior to entry
Dosing: Peptide T 2 mg administered intranasally three times a day for 6 months versus similarly administered placebo.11,12
Note: During this study, participant cerebrospinal fluid (CSF) and peripheral blood samples were frozen and stored. At a later time, the stored CSF and blood samples were used to conduct a retrospective analysis on the ability of peptide T to reduce viral load in a subgroup of participants from the original trial sample.6,7
(See references cited above for information on study results.)


Monomeric DAPTA (reformulation of peptide T)

Study Identifiers: NCT00951743
Phase: II
Study Purpose: Study to evaluate the safety and toxicity of mDAPTA and ability of mDAPTA to eliminate treatment-resistant HIV in peripheral blood mononuclear cells (PBMCs)
Study Population: HIV-infected, treatment-experienced adults receiving ART for at least 6 months and with suppressed viral loads of less than 200 copies/mL for at least 3 months prior to study entry
Dosing: mDAPTA 0.01 mg administered intranasally twice daily for 24 weeks versus similarly administered placebo, each in combination with ART.13


Adverse Events


In a small study investigating the antiviral and immune benefits of peptide T in 11 HIV-infected participants, peptide T was considered safe, with no drug-associated toxicities reported. No nasal pathologies were detected.10

In the Phase II study of peptide T in patients with HIV-associated cognitive impairment, researchers indicated no "clinically significant" toxic effects associated with peptide T use were noted. However, significant differences in the severity of instances of mood disturbance occurred in the peptide T group versus the placebo group (seven Grade 3 events occurred in the peptide T group versus one in the placebo group). Investigators indicated that this difference could be attributed to more severe mood disturbances at study entry in the peptide T arm participants than in the placebo arm participants. In addition, rash was significantly more severe in the peptide T group than in the placebo group. Participants receiving peptide T had a higher prevalence (borderline significant) of nasal congestion, proteinuria, and eosinophilia than participants receiving placebo.11


Drug Interactions


Drug interactions related to adaptavir use are currently unknown.

 


References


  1. United States National Library of Medicine. ChemIDplus Advanced. Available at: http://chem.sis.nlm.nih.gov/chemidplus/rn/106362-34-9. Last accessed on June 17, 2015.
  2. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. Available at: http://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Last accessed on June 17, 2015.
  3. RAPID Pharmaceuticals: Press Release, dated March 4, 2014. RAPID Acquires All Peptide T Clinical Data. Available at: http://www.rapidpharma.com/rapid-acquires-all-peptide-t-clinical-data/. Last accessed on June 17, 2015.
  4. RAPID Pharmaceuticals website. Monomeric DAPTA – the long path to discovery. Available at: http://www.rapidpharma.com/en/research-developement/technology-platform/path-to-discovery.html. Last accessed on March 31, 2014.
  5. Polianova MT, Ruscetti FW, Pert CB, Ruff MR. Chemokine receptor-5 (CCR5) is a receptor for the HIV entry inhibitor peptide T (DAPTA). Antiviral Res. 2005 Aug;67(2):83-92. Available at: http://www.researchgate.net/profile/Maria_Polianova/publication/8658079_Update_on_D-ala-peptide_T-amide_%28DAPTA%29_a_viral_entry_inhibitor_that_blocks_CCR5_chemokine_receptors/links/5436af3e0cf2643ab9881308.pdf. Last accessed on June 17, 2015.
  6. Pollicita M, Ruff MR, Pert CB, et al. Profound anti-HIV-1 activity of DAPTA in monocytes/macrophages and inhibition of CCR5-mediated apoptosis in neuronal cells. Antivir Chem Chemother. 2007;18(5):285-95. Available at: http://avc.sagepub.com/content/18/5/285.long. Last accessed on June 17, 2015.
  7. Goodkin K, Vitiello B, Lyman WD, et al. Cerebrospinal and peripheral human immunodeficiency virus type 1 load in a multisite, randomized, double-blind, placebo-controlled trial of D-Ala1-peptide T-amide for HIV-1-associated cognitive-motor impairment. J Neurovirol. 2006 Jun;12(3):178-89. Available at: http://www.researchgate.net/profile/Benedetto_Vitiello/publication/6909865_Cerebrospinal_and_peripheral_human_immunodeficiency_virus_type_1_load_in_a_multisite_randomized_double-blind_placebo-controlled_trial_of_D-Ala1-peptide_T-amide_for_HIV-1-associated_cognitive-motor_impairment/links/09e4150805c0ab6304000000.pdf. Last accessed on June 17, 2015.
  8. Agrawal L, Ducoudret O, Baichoo N, Laznicka M, Ruff M, Pert C. mDAPTA, a potent CCR5 receptor blocker, prevents viral recovery from CD8-depleted patient PBMCs with VL< 50 background. Abstract presented at: 18th International AIDS Conference; July 18-23, 2010; Vienna, Austria. Abstract TUPE0017. Available at: http://pag.aids2010.org/Abstracts.aspx?AID=10103. Last accessed on June 17, 2015.
  9. Ruff MR, Smith C, Kingan T, et al. Pharmacokinetics of peptide T in patients with acquired immunodeficiency syndrome (AIDS). Prog Neuropsychopharmacol Biol Psychiatry. 1991;15(6):791-801. Available at: http://www.ncbi.nlm.nih.gov/pubmed/1763193. Last accessed on June 17, 2015.
  10. Polianova MT, Ruscetti FW, Pert CB, et al. Antiviral and immunological benefits in HIV patients receiving intranasal peptide T (DAPTA). Peptides. 2003 Jul;24(7):1093-8. Available at: http://www.rapidpharma.com/uploads/media/2003-02_Publication.pdf. Last accessed on March 31, 2014.
  11. Heseltine PN, Goodkin K, Atkinson JH, et al. Randomized Double-blind Placebo-Controlled Trial of Peptide T for HIV-Associated Cognitive Impairment. Arch Neurol. 1998 Jan;55(1):41-51. Available at: http://archneur.jamanetwork.com/article.aspx?articleid=773550. Last accessed on June 17, 2015.
  12. National Institute of Mental Health (NIMH). Phase II Study of the Efficacy of Peptide T in HIV-Positive Individuals With Cognitive Impairment. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 17, 2000. NLM Identifier: NCT00000392. Available at: https://www.clinicaltrials.gov/ct2/show/NCT00000392. Last accessed on June 17, 2015.
  13. Rapid Laboratories Inc. Safety and Efficacy of ADAPTAVIR's Ability to Eliminate Treatment-Resistant Infectious Virus in the Blood Cellular Reservoir (PBMCs) of HIV Patients With Suppressed Plasma Viral Load. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 31, 2009. NLM Identifier: NCT00951743. Available at: https://www.clinicaltrials.gov/ct2/show/NCT00951743. Last accessed on June 17, 2015.
 


Last Reviewed: June 17, 2015

Last Updated: June 17, 2015


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