Study of Single IV Administration of P2G12

NCT02923999 | Unknown Phase 1 DMC

• 2 other identifiers: 14.02312016-001817-25
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

A randomised phase I trial of a monoclonal antibody which neutralises HIV-1 (P2G12) to be given as a single intravenous infusion to healthy human volunteers to assess the safety and reactogenicity

Conditions

HIV Infection

Keywords

HIV; MAB; PLANT

Outcome Measures

Primary Outcomes (2)

• Number of participants with treatment-related adverse events and serious adverse events assessed by CTCAE v4.0.

  three months

• Number of participants with local and systemic reactogenicity signs and symptoms post-infusion

  three months

Secondary Outcomes (1)

• Serum concentration of P2G12 in participants in the active study cohorts

  three months

Study Arms (3)

Dose cohort 1

EXPERIMENTAL

P2G12 0.125g

Drug: P2G12 Dose Cohort 1

Dose cohort 2

EXPERIMENTAL

P2G12 0.25g

Drug: P2G12 Dose Cohort 2

Dose cohort 3

EXPERIMENTAL

P2G12 0.5g

Drug: P2G12 Dose Cohort 3

Interventions

P2G12 Dose Cohort 1 DRUG

single dose of intravenous infusion: 0.125g of the P2G12 human monoclonal antibody

Also known as: human monoclonal antibody

Dose cohort 1

P2G12 Dose Cohort 2 DRUG

single dose of intravenous infusion: 0.25g of the P2G12 human monoclonal antibody

Also known as: human monoclonal antibody

Dose cohort 2

P2G12 Dose Cohort 3 DRUG

single dose of intravenous infusion: 0.5g of the P2G12 human monoclonal antibody

Also known as: human monoclonal antibody

Dose cohort 3

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Volunteers aged between 18 and 45 years on the day of screening
• Available for follow-up for the duration of the study
• Willing and able to give written informed consent
• At low risk of HIV and willing to remain so for the duration of the study defined as:
• no history of injecting drug use in the previous ten years
• no gonorrhoea or syphilis in the last six months
• no high risk partner (e.g. injecting drug use, HIV positive partner) either currently or within the past six months
• no unprotected anal intercourse in the last six months, outside a relationship with a regular partner known/presumed to be HIV negative
• no unprotected vaginal intercourse in the last six months outside a relationship with a regular known/presumed HIV negative partner
• Willing to undergo a HIV test
• If sexually active, using an effective method of contraception with partner (combined oral contraceptive pill; injectable or implanted contraceptive; any IUCD/IUS; consistent record with condoms if using these; physiological or anatomical sterility in self or partner) from 14 days prior to the first infusion until 4 months after, and willing to undergo urine pregnancy tests as per schedule
• Agree to abstain from donating blood for three months after the end of their participation in the trial, or longer if necessary
• Registered with a GP
• Satisfactory response received from GP before randomisation

You may not qualify if:

• Pregnant or lactating
• Clinically relevant abnormality on history or examination including
• history of grand-mal epilepsy
• skin disorder might prevent insertion of IV line
• liver disease with inadequate hepatic function (grade 1 or greater as described in appendix 3)
• haematological, metabolic, gastrointestinal or cardio-pulmonary disorders
• uncontrolled infection; immunodeficiency or use of immunosuppressives in preceding 3 months (including systemic steroids for longer than 14 days)
• history of renal disease
• history of autoimmune disease
• Known hypersensitivity to any component of the infusion used in this trial, or have severe or multiple allergies to drugs or pharmaceutical agents
• History of severe local or general reaction to vaccination which according to the investigators judgement might prevent participation
• Receipt of blood products or immunoglobulin within 4 months of screening
• Participation in another trial of a medicinal product, completed less than 30 days prior to enrolment
• HIV 1/2 positive or indeterminate on screening
• Positive for hepatitis B surface antigen, hepatitis C antibody or serology indicating active syphilis requiring treatment

Sponsors & Collaborators

• St George's, University of London: lead

Study Sites (1)

St George's NHS Healthcare Trust

London, SW170RE, United Kingdom

Location

Related Publications (12)

• Mascola JR, Montefiori DC. The role of antibodies in HIV vaccines. Annu Rev Immunol. 2010;28:413-44. doi: 10.1146/annurev-immunol-030409-101256.

  PMID: 20192810 RESULT

• 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 RESULT

• Mascola JR, Haynes BF. HIV-1 neutralizing antibodies: understanding nature's pathways. Immunol Rev. 2013 Jul;254(1):225-44. doi: 10.1111/imr.12075.

  PMID: 23772623 RESULT

• Mascola JR, Stiegler G, VanCott TC, Katinger H, Carpenter CB, Hanson CE, Beary H, Hayes D, Frankel SS, Birx DL, Lewis MG. Protection of macaques against vaginal transmission of a pathogenic HIV-1/SIV chimeric virus by passive infusion of neutralizing antibodies. Nat Med. 2000 Feb;6(2):207-10. doi: 10.1038/72318.

  PMID: 10655111 RESULT

• Armbruster C, Stiegler GM, Vcelar BA, Jager W, Michael NL, Vetter N, Katinger HW. A phase I trial with two human monoclonal antibodies (hMAb 2F5, 2G12) against HIV-1. AIDS. 2002 Jan 25;16(2):227-33. doi: 10.1097/00002030-200201250-00012.

  PMID: 11807307 RESULT

• Armbruster C, Stiegler GM, Vcelar BA, Jager W, Koller U, Jilch R, Ammann CG, Pruenster M, Stoiber H, Katinger HW. Passive immunization with the anti-HIV-1 human monoclonal antibody (hMAb) 4E10 and the hMAb combination 4E10/2F5/2G12. J Antimicrob Chemother. 2004 Nov;54(5):915-20. doi: 10.1093/jac/dkh428. Epub 2004 Sep 29.

  PMID: 15456731 RESULT

• Ledgerwood JE, Coates EE, Yamshchikov G, Saunders JG, Holman L, Enama ME, DeZure A, Lynch RM, Gordon I, Plummer S, Hendel CS, Pegu A, Conan-Cibotti M, Sitar S, Bailer RT, Narpala S, McDermott A, Louder M, O'Dell S, Mohan S, Pandey JP, Schwartz RM, Hu Z, Koup RA, Capparelli E, Mascola JR, Graham BS; VRC 602 Study Team. Safety, pharmacokinetics and neutralization of the broadly neutralizing HIV-1 human monoclonal antibody VRC01 in healthy adults. Clin Exp Immunol. 2015 Dec;182(3):289-301. doi: 10.1111/cei.12692. Epub 2015 Sep 24.

  PMID: 26332605 RESULT

• Mehandru S, Vcelar B, Wrin T, Stiegler G, Joos B, Mohri H, Boden D, Galovich J, Tenner-Racz K, Racz P, Carrington M, Petropoulos C, Katinger H, Markowitz M. Adjunctive passive immunotherapy in human immunodeficiency virus type 1-infected individuals treated with antiviral therapy during acute and early infection. J Virol. 2007 Oct;81(20):11016-31. doi: 10.1128/JVI.01340-07. Epub 2007 Aug 8.

  PMID: 17686878 RESULT

• Trkola A, Kuster H, Rusert P, Joos B, Fischer M, Leemann C, Manrique A, Huber M, Rehr M, Oxenius A, Weber R, Stiegler G, Vcelar B, Katinger H, Aceto L, Gunthard HF. Delay of HIV-1 rebound after cessation of antiretroviral therapy through passive transfer of human neutralizing antibodies. Nat Med. 2005 Jun;11(6):615-22. doi: 10.1038/nm1244. Epub 2005 May 8.

  PMID: 15880120 RESULT

• Ma JK, Drossard J, Lewis D, Altmann F, Boyle J, Christou P, Cole T, Dale P, van Dolleweerd CJ, Isitt V, Katinger D, Lobedan M, Mertens H, Paul MJ, Rademacher T, Sack M, Hundleby PA, Stiegler G, Stoger E, Twyman RM, Vcelar B, Fischer R. Regulatory approval and a first-in-human phase I clinical trial of a monoclonal antibody produced in transgenic tobacco plants. Plant Biotechnol J. 2015 Oct;13(8):1106-20. doi: 10.1111/pbi.12416. Epub 2015 Jul 3.

  PMID: 26147010 RESULT

• UNAIDS Fact sheet 2015

  RESULT

• WHO Global Health Observatory

  RESULT

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

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

Study Officials

• Catherine Cosgrove

  St George's, University of London

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Catherine Cosgrove

CONTACT

02087252316; ccosgrov@sgul.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2016
• First Posted: October 5, 2016
• Study Start: August 1, 2019
• Primary Completion: August 1, 2020
• Study Completion: December 1, 2020
• Last Updated: January 18, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)