NCT02500849

Brief Summary

The purpose of the study is to evaluate the safety and feasibility of administering SB-728mR-HSPC after conditioning with busulfan.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
12

participants targeted

Target at below P25 for phase_1 hiv

Timeline
3mo left

Started Mar 2016

Longer than P75 for phase_1 hiv

Geographic Reach
1 country

5 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress97%
Mar 2016Aug 2026

First Submitted

Initial submission to the registry

March 16, 2015

Completed
4 months until next milestone

First Posted

Study publicly available on registry

July 17, 2015

Completed
8 months until next milestone

Study Start

First participant enrolled

March 10, 2016

Completed
10.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 24, 2026

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 24, 2026

Last Updated

October 9, 2025

Status Verified

October 1, 2025

Enrollment Period

10.5 years

First QC Date

March 16, 2015

Last Update Submit

October 8, 2025

Conditions

HIV

Keywords

Gene therapyAcquired Immunodeficiency SyndromeHIV InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesSexually Transmitted Diseases, ViralSexually Transmitted DiseasesImmunologic Deficiency SyndromesImmune System DiseasesBusulfanPharmacologic Actions

Outcome Measures

Primary Outcomes (1)

  • Toxicity in subjects who received SB-728mR-HSPC after each busulfan dose level

    18 months

Secondary Outcomes (1)

  • Number of CD34+ HSPC collected, gene modified, and released throughout the manufacturing process

    Approximately first 1-2 months on study

Other Outcomes (9)

  • Detection of CCR5 modified HSPC in bone marrow

    Up to Month 12

  • Time to hematological recovery as measured by neutrophil and platelet engraftment time

    Up to Year 5

  • Changes in CD4+ T-cell percentage after SB-728mR-HSPC infusion

    Up to Year 5

  • +6 more other outcomes

Study Arms (2)

Cohort 1:

EXPERIMENTAL

target busulfan AUC levels: 8,000 µM\*min (+/- 1,000)

Genetic: SB-728mR-HSPC Infusion 3 days following busulfan conditioning

Cohort 2:

EXPERIMENTAL

busulfan AUC levels: 12,000 µM\*min (+/- 1,000)

Genetic: SB-728mR-HSPC Infusion 3 days following busulfan conditioning

Interventions

SB-728mR-HSPC Infusion 3 days following busulfan conditioningGENETIC
Also known as: busulfan
Cohort 1:Cohort 2:

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Maximum age 75 years for cohort 1 and 65 years for cohort 2.
  • HIV-1 R5 seropositive with no evidence of CXCR4-tropic virus.
  • On cART with undetectable HIV-1 (\<20 gc/ml HIV-1 RNA) for at least 12 months prior to screening evaluations.
  • CD4+ T-cell counts ≥200 cells/µL and ≤750 cells/µL.
  • No psychosocial conditions that would hinder study compliance and follow-up.
  • Absence of clinically significant cardiomyopathy, congestive heart failure.
  • Secondary Eligibility Criteria (for registration):
  • Complete G-CSF/Plerixafor mobilization of HSPC.
  • Collect ≥7.5 x 10\^6 CD34+ cells/kg in two aphereses.
  • The SB-728mR-HSPC product passed all release testing

You may not qualify if:

  • Use of AZT or maraviroc in the cART regimen.
  • History of significant hematologic diseases such as leukemia, myelodysplasia, coagulopathy, and thromboembolism.
  • Any AIDS-related opportunistic infection occurring within the past year such as tuberculosis, cryptococcosis and for which treatment has been unsuccessful as determined by the Principal Investigator.
  • AIDS-related syndromes, infectious or otherwise, if perceived to cause excessive risk for morbidity post-HSPC infusion, as determined by the Principal Investigator.
  • Patients with active HBV or HCV infection, i.e., HBV DNA and HCV RNA in blood, are excluded. Those with inactive, but past infection with HBV (positive HBV surface antigen or HBV surface antibody) or inactive HCV (positive HCV antibody), must have no cirrhosis, as determined by abdominal ultrasound with elastography.
  • Active CMV retinitis or other active CMV-related organ dysfunction.
  • CXCR4-tropic virus.
  • Pregnant or nursing women.
  • Any history of HIV-associated encephalopathy; dementia of any kind; seizures in the past 12 months; any perceived inability to directly provide informed consent.
  • Participants may not be receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy. Participation in prior investigational drug or medical device study within the previous 45 days.
  • Current or history of immunomodulatory agent or steroid use.
  • Prior therapy with HIV vaccine or gene therapy product.
  • History of alcohol or substance abuse for the previous 12 months.
  • Participants with active malignancies. However, participants with skin cancers, namely basal cell or squamous cell carcinoma, and malignancies treated with curative intent having no known active disease present for ≥2 years, may be eligible.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

UCLA CARE Center

Los Angeles, California, 90035, United States

Location

Mills Clinical Research

Los Angeles, California, 90069, United States

Location

Quest Clinical Research

San Francisco, California, 94115, United States

Location

Circle CARE Center, LLC

Norwalk, Connecticut, 06850, United States

Location

Related Publications (1)

  • DiGiusto DL, Cannon PM, Holmes MC, Li L, Rao A, Wang J, Lee G, Gregory PD, Kim KA, Hayward SB, Meyer K, Exline C, Lopez E, Henley J, Gonzalez N, Bedell V, Stan R, Zaia JA. Preclinical development and qualification of ZFN-mediated CCR5 disruption in human hematopoietic stem/progenitor cells. Mol Ther Methods Clin Dev. 2016 Nov 9;3:16067. doi: 10.1038/mtm.2016.67. eCollection 2016.

    PMID: 27900346DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency SyndromeHIV InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesSexually Transmitted Diseases, ViralSexually Transmitted DiseasesImmunologic Deficiency SyndromesImmune System Diseases

Interventions

Busulfan

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsLentivirus InfectionsSlow Virus DiseasesGenital DiseasesUrogenital DiseasesDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Butylene GlycolsGlycolsAlcoholsOrganic ChemicalsMesylatesAlkanesulfonatesAlkanesulfonic AcidsAlkanesHydrocarbons, AcyclicHydrocarbonsSulfonic AcidsSulfur AcidsSulfur Compounds

Study Officials

  • Amrita Y. Krishnan, MD

    City of Hope Medical Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 16, 2015

First Posted

July 17, 2015

Study Start

March 10, 2016

Primary Completion (Estimated)

August 24, 2026

Study Completion (Estimated)

August 24, 2026

Last Updated

October 9, 2025

Record last verified: 2025-10

Locations

US(5)