Autologous CD4 T-Cells in HIV (C34-CXCR4)

NCT03020524 | Completed Early Phase 1 Results

• 1 other identifier: 826035
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

A single cohort, open-label pilot study of the safety and tolerability of a single infusion of autologous CD4+ T-cells genetically modified with an HR2, C34-peptide conjugated to the CXCR4 N-terminus using a lentiviral vector in HIV-infected subjects. This is a first in human study of C34-CXCR4 T cells

Conditions

Hiv

Outcome Measures

Primary Outcomes (1)

• The Number of Subjects With Treatment Related Adverse Events

  assessed by DAIDS AE grading table v2.0 November 2014

  one year

Secondary Outcomes (4)

• Compare the Percentage of Enriched Modified Cells C34-CXCR4 Modifiec T- Cells

  2 weeks post infusion, prior to ARV reinitiation, weeks 12, 16 and 20

• Compare the Change Between CD4 Count

  Baseline, week 2 post infusion, prior to ARV initiation, weeks 12, 16 20

• Compare Viral Set Point Log 10 HIV RNA Level

  week 2 post infusion, prior to ARV initiation, week 12, 16, 20

• Evaluate Cell Mediated Response (Immunogenicity) Using Flow Cytometry

  baseline through 1 year

Study Arms (3)

Dose level 1:

EXPERIMENTAL

Autologous CD4 T-Cells0.8-1x10\^9 transduced CD4+T-cells administered IV as a single dose

Biological: Autologous CD4 T-Cells

Dose level 2

ACTIVE COMPARATOR

Autologous CD4 T-Cells 2.4-3x10\^9 transduced CD4+ T-cells administered IV as a single dose

Biological: Autologous CD4 T-Cells

Dose level 3

ACTIVE COMPARATOR

Autologous CD4 T-Cells 0.8-1x10\^10 transduced CD4+ T-cells administered IV as a single dose

Biological: Autologous CD4 T-Cells

Interventions

Autologous CD4 T-Cells BIOLOGICAL

all participants will receive a single infusion of C34-CXCR4-modified CD4+ T-cells at one of 3 dose levels. The first 3 subjects will receive dose level 1 of 0.8-1x109 transduced CD4+T-cells. Provided no dose limiting toxicity (DLT) is seen at the first dose level, the next 3 subjects will receive infusion at the 2nd dose level of 2.4-3x109 transduced CD4+ T-cells. If no DLT occurs at that dose, the final 3 subjects will receive the 3rd dose level of 0.8-1x1010 transduced CD4+ T-cells. In the event of a DLT (grade 3 or higher unexpected, related AE) recruitment will be paused pending DSMB decision

Dose level 1:; Dose level 2; Dose level 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to enrollment and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA VL.
• Ability and willingness of subject to provide informed consent.
• Men and women ages ≥18 years.
• Clinically stable on their first or second HAART regimen. Changes while the patient HIV viral load is undetectable does not count toward the number of ART regimens used, only changes made for virologic failure (for example an individual switching from an NNRTI-based regimen to an integrase inhibitor based regimen while the HIV viral load is undetectable will still be in their first regimen). Site investigator anticipates that a fully active alternative ART regimen could be constructed in the event of virologic failure on the current ART regimen.The current regimen should have no changes within 4 weeks of enrollment. Subjects must be willing to continue on current antiretroviral therapy for the duration of the study except for the duration of the 16 week analytical treatment interruption. (NOTE: changes to safely begin the treatment interruption are permitted).
• Screening HIV-1 RNA that is ≤50 copies/mL using a FDA-approved assay performed by any laboratory that has a CLIA certification or its equivalent within 30 days prior to enrollment.
• HIV-1 RNA ≤50 copies/mL using a FDA-approved assay for at least 24 weeks prior to enrollment performed by any laboratory that has a CLIA certification or its equivalent.
• NOTE: HIV-RNA must be measured at least once in the last 24 weeks and at least 3 days before the screening measure. Single determinations that are between \>50 and \<400 copies/mL (ie, blips) are allowed as long as the preceding and subsequent determinations are ≤50 copies/mL. The screening value may serve as the subsequent determination ≤50 copies/mL following a blip
• NOTE: subjects who have participated in other trials using ATI's will be permitted since detectable virus during the interruption does not represent virologic failure. These subjects should have at least 24 weeks of VL \<50 copies/mL.
• Screening CD4+ T-cell count ≥450 cells/ mm3 within 30 days of enrollment.
• Started ART with nadir CD4+ ≥200 cells/ mm3.
• The following laboratory values obtained within 30 days prior to enrollment meeting the following criteria:
• Absolute neutrophil count (ANC) ≥1000 cells/mm3
• Hemoglobin:≥10.0(males); ≥9.5 (females) g/dL
• Platelet count: 100,000/mm3
• Calculated creatinine clearance ≥50 mL/min estimated by the Cockcroft-Gault equation

You may not qualify if:

• Acute or chronic hepatitis B or hepatitis C infection
• Current or prior AIDS diagnosis.
• History of cancer or malignancy, with the exception of successfully treated basal cell or squamous cell carcinoma of the skin
• History or any features on physical examination indicative of active or unstable cardiac disease or hemodynamic instability.
• NOTE: Subjects with a history of cardiac disease may participate with a physician's approval.
• History or any features on physical examination indicative of a bleeding diathesis
• Have been previously treated with any HIV experimental vaccine within 6 months prior to enrollment, or any previous gene therapy using an integrating vector.
• NOTE: Subjects treated with placebo in an HIV vaccine study will not be excluded if documentation that they received placebo is provided.
• Use of chronic systemic corticosteroids, hydroxyurea, or immunomodulating agents (e.g., interleukin-2, interferon-alpha or gamma, granulocyte colony stimulating factors, etc.) within 30 days prior to enrollment.
• Breast-feeding, pregnant, or unwilling to use acceptable methods of birth control.
• Anticipated use of aspirin, dipyridamole, warfarin or any other medication that is likely to affect platelet function or other aspects of blood coagulation during the 2-week period prior to leukapheresis
• Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
• Serious illness requiring systemic treatment and/or hospitalization within 30 days prior to enrollment
• Receipt of vaccination within 30 days prior to enrollment.
• NOTE: It is recommended that subjects enrolling into this study should have completed their routine vaccinations (hepatitis A, hepatitis B, pneumococcus, and tetanus diphtheria booster) at least 30 days prior to enrollment

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

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

Results Point of Contact

• Title: Regulatory Lead
• Organization: University of Pennsylvania

psom-ind-ide@pobox.upenn.edu

215.662.4484

Study Officials

• Pablo Tebas, MD

  University of Pennaylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2017
• First Posted: January 13, 2017
• Study Start: January 1, 2017
• Primary Completion: November 1, 2019
• Study Completion: March 1, 2020
• Last Updated: November 15, 2022
• Results First Posted: November 9, 2020

Record last verified: 2022-11

Locations

US (1)