A Dose-Escalation Study of MDX-010 Administered Monthly as Immunotherapy in Subjects Infected With Human Immunodeficiency Virus (HIV)

A Phase I, Open-Label, Dose-Escalation Study of MDX-010 Administered Monthly as Immunotherapy in Subjects Infected With Human Immunodeficiency Virus

The purpose of this study is to assess the safety and tolerability of 2 or 4 doses of MDX-010 in HIV-infected subjects

Study Overview

• Status: Completed
• Conditions: Human Immunodeficiency Virus (HIV)
• Intervention / Treatment: Biological: MDX-010

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Tower ID Medical Associates
    • San Francisco, California, United States, 94115
      • Quest Clinical Research
  • Florida
    • Miami, Florida, United States, 33137
      • Care Resource
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center
  • Texas
    • Houston, Texas, United States, 77098
      • Shannon Schrader, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Detectable HIV viremia (HIV-1 RNA level between 1,000 and 100,000 copies/mL)
• CD4 count greater than or equal to 100 cells/mm3
• Current antiretroviral therapy regimen following at least 2 previous changes for documented virologic failure
• Documented resistance tests demonstrating the presence of at least 1 mutation to each major therapeutic class of antiretroviral therapy
• No significant organ compromise

Exclusion Criteria:

• Initiation of any new medications that might reasonably affect the immune response or viral load within 4 weeks prior to screening
• Tetanus booster immunization within 2 months of screening, or a history of anaphylaxis or severe local reaction to the tetanus vaccine
• History of autoimmune disease at risk for recurrence
• Current malignancy, except Stage A or B cervical carcinoma or basal cell carcinoma
• Chronic viral hepatitis, due to Hepatitis B or Hepatitis C undergoing current treatment or Hepatitis B DNA greater than 25 pg/cc or Hepatitis C RNA greater than 20,000 IU/cc
• Currently undergoing treatment or prophylaxis for tuberculosis infection
• Chronic active infectious disease (other than HIV)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 2; Specified dose on specified days	Biological: MDX-010; Specified dose on specified days; Other Names: BMS-734016; Ipilimumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of treatment induced dose limiting toxicities (DLTs)	Up to 141 days
Grade of treatment induced DLTs	Up to 141 days
Number of treatment emergent AEs (adverse events)	Up to 141 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum plasma concentration observed post-dose (Cmax)	Up to 141 days
Time of maximum plasma concentration observed post-dose (Tmax)	Up to 141 days
HIV Ribonucleic Acid (RNA) level	Up to 141 days
CD4 (cluster of differentiation) T (thymus) cell cytokine responses to Human Immunodeficiency Virus-1 (HIV-1) antigens	Up to 141 days
CD4 T cell cytokine responses to Candida antigen	Up to 141 days
CD4 T cell cytokine responses to tetanus antigen	Up to 141 days
CD8 (cluster of differentiation) T cell cytokine responses to HIV-1 antigens	Up to 141 days
CD8 T cell cytokine responses to Candida antigen	Up to 141 days
CD8 T cell cytokine responses to tetanus antigen	Up to 141 days
Lymphocyte Proliferation Assay (LPA) to HIV-1 antigens	Up to 141 days
LPA to Candida antigens	Up to 141 days
LPA to tetanus antigens	Up to 141 days
Anti-tetanus toxin antibody level	Up to 141 days
Number of CD4 T cells	Up to 141 days
Number of CD8 T cells	Up to 141 days

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Collaborators: Medarex

Publications and helpful links

General Publications

• Colston E, Grasela D, Gardiner D, Bucy RP, Vakkalagadda B, Korman AJ, Lowy I. An open-label, multiple ascending dose study of the anti-CTLA-4 antibody ipilimumab in viremic HIV patients. PLoS One. 2018 Jun 7;13(6):e0198158. doi: 10.1371/journal.pone.0198158. eCollection 2018.

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2003
• Primary Completion (Actual): February 21, 2006
• Study Completion (Actual): February 21, 2006

Study Registration Dates

• First Submitted: January 17, 2018
• First Submitted That Met QC Criteria: January 17, 2018
• First Posted (Actual): January 23, 2018

Study Record Updates

• Last Update Posted (Actual): January 23, 2018
• Last Update Submitted That Met QC Criteria: January 17, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Ipilimumab
• Other Study ID Numbers: MDX010-10

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No