123I Radiolabeled 3BNC117

NCT03468582 | Completed Early Phase 1

• 1 other identifier: 2017-01003
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The conventional way to control HIV infection is the usage of a drug cocktail capable of suppressing the viral replication cycle, commonly known as antiretroviral therapy (ART). Despite effective ART it is not possible to eradicate HIV. The virus hides in particular cells to form the latent HIV-reservoir.\[1-9\] Studies that emphasise on revealing hidden reservoirs would aid in designing novel therapeutic strategies for controlling HIV infection. Molecular imaging by SPECT/CT has the potential to reveal hidden reservoirs of HIV virus that are not eliminated by currently used drugs capable of suppressing and thereby controlling the viral replication cycle in HIV infected patients. New approaches, necessary to prevent and treat HIV-1 infection, are gradually emerging. A new generation of highly potent broadly neutralizing antibodies (bN/Abs) may represent a promising approach to combating HIV-1 infection.\[10\] The broadly neutralizing antibody 3BNC117 antibody that can mimic human CD4 binding targeted against the HIV gp120 envelope protein has been tested in various clinical trials.\[11-14\] It has found to be safe and effective in reducing viraemia and to improve host humoral responses in HIV-1 infected individuals, and to have effect on viral rebound in patients who are kept off antiretroviral treatment briefly for experimental purpose. Imaging of simian immunodeficiency virus (SIV) infection by PET/CT has been successfully performed in nonhuman primates with a 64Cu-labeled SIV gp120-specific antibody called 7D3.\[15\] This study aims to use a similar approach in human with the 3BNC117 antibody. The 3BNC117 antibody has been successfully radiolabeled with iodine 123. The half-life of this radioisotope is appropriate for antibody imaging in nuclear medicine. Radiolabeled 123I 3BNC117 was shown to keep a good immunoreactivity for gp120. By using state of the art SPECT scanner a semi-quantitative image will be obtained. In addition, the absence of any chelator and the well known use of iodine-123 in clinic make it suitable for human intervention. No HIV imaging in human has been achieved yet, which is however fundamental to understand some key steps in the pathogenesis of HIV-induced immunodeficiency. This research opens promising opportunities for drug and vaccine development. Indeed, identification of virus reservoirs in treated patients would facilitate the development of strategies for eradicating these reservoirs or for extending latency period.

Conditions

Human Immunodeficiency Virus

Outcome Measures

Primary Outcomes (1)

• Absorbed dose per Organ mGy/MBq

  Absorbed dose in the organs at risk is calculated from planar images after organ contouring using OLINDA / EXM software; additionally blood samples (2 mL) is taken before each gamma camera scan to estimate the dose to bone marrow. The blood samples are needed to derive the radiation dose exposure to the bone marrow through the measure of the count rate in the blood sample using a calibrated gamma counter. MIRD (medical internal radiation dosimetry) based methods will provide the contribution to the bone marrow radiation exposure from activity present into the blood.\[19\] No other additional analysis will be performed on these blood samples.

  3 month

Secondary Outcomes (1)

• total number of lesions

  3 month

Study Arms (1)

123I radiolabeled 3BNC117

EXPERIMENTAL

123I radiolabeled 3BNC117

Combination Product: 123I radiolabeled 3BNC117

Interventions

123I radiolabeled 3BNC117 COMBINATION_PRODUCT

123I radiolabeled 3BNC117

123I radiolabeled 3BNC117

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subject newly diagnosed with HIV in a chronic phase requiring the introduction of an antiretroviral treatment (ART)
• Age 18 to 55
• HIV-1 infection confirmed by ELISA and immunoblot
• Plasma HIV-1 RN/A \> 5000 copies/ml
• Current CD4 cell count \> 200 cells/μl
• Ability and willingness to provide written informed consent

You may not qualify if:

• Primary infected HIV
• Currently on ART
• Participation in another clinical study of an investigational product currently or within past 30 days
• Pregnancy or lactation;
• History of systemic corticosteroids, immunosuppressive anti-cancer, or other medications considered significant by the trial physician within the last 6 months;
• Patient report, or chart history, of significant coronary artery disease, myocardial infarction, percutaneous coronary intervention with placement of cardiac stents;
• Uncontrolled hypertension, as defined by a systolic blood pressure \> 180 and/or diastolic blood pressure \> 120, in the presence or absence of anti-hypertensive medications;
• Any other clinically significant acute or chronic medical condition, such as autoimmune diseases, that in the opinion of the investigator would preclude participation;
• Laboratory abnormalities in the parameters listed below:
• Absolute neutrophil count ≤1 G/l
• Hemoglobin ≤ 10 gm/dL
• Platelet count ≤125 G/l
• ALT ≥ 2.0 x ULN
• AST ≥ 2.0 x ULN
• Total bilirubin ≥ 1.5 ULN

Sponsors & Collaborators

• University of Lausanne Hospitals: lead

Study Sites (1)

Centre Hospitalier Universitaire Vaudois

Lausanne, Canton of Vaud, 1011, Switzerland

Location

Related Publications (19)

• Chun TW, Stuyver L, Mizell SB, Ehler LA, Mican JA, Baseler M, Lloyd AL, Nowak MA, Fauci AS. Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy. Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13193-7. doi: 10.1073/pnas.94.24.13193.

  PMID: 9371822 BACKGROUND

• Chun TW, Carruth L, Finzi D, Shen X, DiGiuseppe JA, Taylor H, Hermankova M, Chadwick K, Margolick J, Quinn TC, Kuo YH, Brookmeyer R, Zeiger MA, Barditch-Crovo P, Siliciano RF. Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection. Nature. 1997 May 8;387(6629):183-8. doi: 10.1038/387183a0.

  PMID: 9144289 BACKGROUND

• Finzi D, Hermankova M, Pierson T, Carruth LM, Buck C, Chaisson RE, Quinn TC, Chadwick K, Margolick J, Brookmeyer R, Gallant J, Markowitz M, Ho DD, Richman DD, Siliciano RF. Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science. 1997 Nov 14;278(5341):1295-300. doi: 10.1126/science.278.5341.1295.

  PMID: 9360927 BACKGROUND

• Wong JK, Hezareh M, Gunthard HF, Havlir DV, Ignacio CC, Spina CA, Richman DD. Recovery of replication-competent HIV despite prolonged suppression of plasma viremia. Science. 1997 Nov 14;278(5341):1291-5. doi: 10.1126/science.278.5341.1291.

  PMID: 9360926 BACKGROUND

• Siliciano JD, Kajdas J, Finzi D, Quinn TC, Chadwick K, Margolick JB, Kovacs C, Gange SJ, Siliciano RF. Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4+ T cells. Nat Med. 2003 Jun;9(6):727-8. doi: 10.1038/nm880. Epub 2003 May 18.

  PMID: 12754504 BACKGROUND

• Chomont N, El-Far M, Ancuta P, Trautmann L, Procopio FA, Yassine-Diab B, Boucher G, Boulassel MR, Ghattas G, Brenchley JM, Schacker TW, Hill BJ, Douek DC, Routy JP, Haddad EK, Sekaly RP. HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation. Nat Med. 2009 Aug;15(8):893-900. doi: 10.1038/nm.1972. Epub 2009 Jun 21.

  PMID: 19543283 BACKGROUND

• Buzon MJ, Sun H, Li C, Shaw A, Seiss K, Ouyang Z, Martin-Gayo E, Leng J, Henrich TJ, Li JZ, Pereyra F, Zurakowski R, Walker BD, Rosenberg ES, Yu XG, Lichterfeld M. HIV-1 persistence in CD4+ T cells with stem cell-like properties. Nat Med. 2014 Feb;20(2):139-42. doi: 10.1038/nm.3445. Epub 2014 Jan 12.

  PMID: 24412925 BACKGROUND

• Perreau M, Savoye AL, De Crignis E, Corpataux JM, Cubas R, Haddad EK, De Leval L, Graziosi C, Pantaleo G. Follicular helper T cells serve as the major CD4 T cell compartment for HIV-1 infection, replication, and production. J Exp Med. 2013 Jan 14;210(1):143-56. doi: 10.1084/jem.20121932. Epub 2012 Dec 17.

  PMID: 23254284 BACKGROUND

• Banga R, Procopio FA, Noto A, Pollakis G, Cavassini M, Ohmiti K, Corpataux JM, de Leval L, Pantaleo G, Perreau M. PD-1(+) and follicular helper T cells are responsible for persistent HIV-1 transcription in treated aviremic individuals. Nat Med. 2016 Jul;22(7):754-61. doi: 10.1038/nm.4113. Epub 2016 May 30.

  PMID: 27239760 BACKGROUND

• Klein F, Mouquet H, Dosenovic P, Scheid JF, Scharf L, Nussenzweig MC. Antibodies in HIV-1 vaccine development and therapy. Science. 2013 Sep 13;341(6151):1199-204. doi: 10.1126/science.1241144.

  PMID: 24031012 BACKGROUND

• Scheid JF, Mouquet H, Ueberheide B, Diskin R, Klein F, Oliveira TY, Pietzsch J, Fenyo D, Abadir A, Velinzon K, Hurley A, Myung S, Boulad F, Poignard P, Burton DR, Pereyra F, Ho DD, Walker BD, Seaman MS, Bjorkman PJ, Chait BT, Nussenzweig MC. Sequence and structural convergence of broad and potent HIV antibodies that mimic CD4 binding. Science. 2011 Sep 16;333(6049):1633-7. doi: 10.1126/science.1207227. Epub 2011 Jul 14.

  PMID: 21764753 BACKGROUND

• Caskey M, Klein F, Lorenzi JC, Seaman MS, West AP Jr, Buckley N, Kremer G, Nogueira L, Braunschweig M, Scheid JF, Horwitz JA, Shimeliovich I, Ben-Avraham S, Witmer-Pack M, Platten M, Lehmann C, Burke LA, Hawthorne T, Gorelick RJ, Walker BD, Keler T, Gulick RM, Fatkenheuer G, Schlesinger SJ, Nussenzweig MC. Viraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody 3BNC117. Nature. 2015 Jun 25;522(7557):487-91. doi: 10.1038/nature14411. Epub 2015 Apr 8.

  PMID: 25855300 BACKGROUND

• Schoofs T, Klein F, Braunschweig M, Kreider EF, Feldmann A, Nogueira L, Oliveira T, Lorenzi JC, Parrish EH, Learn GH, West AP Jr, Bjorkman PJ, Schlesinger SJ, Seaman MS, Czartoski J, McElrath MJ, Pfeifer N, Hahn BH, Caskey M, Nussenzweig MC. HIV-1 therapy with monoclonal antibody 3BNC117 elicits host immune responses against HIV-1. Science. 2016 May 20;352(6288):997-1001. doi: 10.1126/science.aaf0972. Epub 2016 May 5.

  PMID: 27199429 BACKGROUND

• Scheid JF, Horwitz JA, Bar-On Y, Kreider EF, Lu CL, Lorenzi JC, Feldmann A, Braunschweig M, Nogueira L, Oliveira T, Shimeliovich I, Patel R, Burke L, Cohen YZ, Hadrigan S, Settler A, Witmer-Pack M, West AP Jr, Juelg B, Keler T, Hawthorne T, Zingman B, Gulick RM, Pfeifer N, Learn GH, Seaman MS, Bjorkman PJ, Klein F, Schlesinger SJ, Walker BD, Hahn BH, Nussenzweig MC, Caskey M. HIV-1 antibody 3BNC117 suppresses viral rebound in humans during treatment interruption. Nature. 2016 Jul 28;535(7613):556-60. doi: 10.1038/nature18929. Epub 2016 Jun 22.

  PMID: 27338952 BACKGROUND

• Santangelo PJ, Rogers KA, Zurla C, Blanchard EL, Gumber S, Strait K, Connor-Stroud F, Schuster DM, Amancha PK, Hong JJ, Byrareddy SN, Hoxie JA, Vidakovic B, Ansari AA, Hunter E, Villinger F. Whole-body immunoPET reveals active SIV dynamics in viremic and antiretroviral therapy-treated macaques. Nat Methods. 2015 May;12(5):427-32. doi: 10.1038/nmeth.3320. Epub 2015 Mar 9.

  PMID: 25751144 BACKGROUND

• Falkowska E, Ramos A, Feng Y, Zhou T, Moquin S, Walker LM, Wu X, Seaman MS, Wrin T, Kwong PD, Wyatt RT, Mascola JR, Poignard P, Burton DR. PGV04, an HIV-1 gp120 CD4 binding site antibody, is broad and potent in neutralization but does not induce conformational changes characteristic of CD4. J Virol. 2012 Apr;86(8):4394-403. doi: 10.1128/JVI.06973-11. Epub 2012 Feb 15.

  PMID: 22345481 BACKGROUND

• Shingai M, Nishimura Y, Klein F, Mouquet H, Donau OK, Plishka R, Buckler-White A, Seaman M, Piatak M Jr, Lifson JD, Dimitrov DS, Nussenzweig MC, Martin MA. Antibody-mediated immunotherapy of macaques chronically infected with SHIV suppresses viraemia. Nature. 2013 Nov 14;503(7475):277-80. doi: 10.1038/nature12746. Epub 2013 Oct 30.

  PMID: 24172896 BACKGROUND

• Aroua A, Samara ET, Bochud FO, Meuli R, Verdun FR. Exposure of the Swiss population to computed tomography. BMC Med Imaging. 2013 Jul 30;13:22. doi: 10.1186/1471-2342-13-22.

  PMID: 23895057 BACKGROUND

• Hindorf C, Glatting G, Chiesa C, Linden O, Flux G; EANM Dosimetry Committee. EANM Dosimetry Committee guidelines for bone marrow and whole-body dosimetry. Eur J Nucl Med Mol Imaging. 2010 Jun;37(6):1238-50. doi: 10.1007/s00259-010-1422-4.

  PMID: 20411259 BACKGROUND

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Giuseppe Pantaleo, MD, PhD

  University of Lausanne Hospitals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of nuclear medicine and molecular imaging department

Model Details: Monocentric, open-label and uncontrolled study

Study Record Dates

• First Submitted: February 12, 2018
• First Posted: March 16, 2018
• Study Start: February 8, 2018
• Primary Completion: January 28, 2020
• Study Completion: January 28, 2020
• Last Updated: January 29, 2020

Record last verified: 2020-01

Locations

CH (1)