Bryostatin-1 Effect on HIV-1 Latency and Reservoir in HIV-1 Infected Patients Receiving Antiretroviral Treatment

NCT02269605 | Completed Phase 1 DMC

• 1 other identifier: BRYOLAT
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Phase I, randomized, double blind, placebo-controlled, dose-finding trial. The trial´s goal is to evaluate two different doses of Bryostatin on HIV-1 latency and reservoir in HIV-1 infected patients receiving antiretroviral treatment.

Conditions

HIV Infection

Keywords

HIV reservoir; Bryostatin

Outcome Measures

Primary Outcomes (1)

• Intracellular HIV-1 RNA (usRNA and msRNA) level before and after bryostatin-1 administration

  Baseline visit and days 2 and 3 after the day of treatment

Secondary Outcomes (4)

• HIV-1 RNA level

  Baseline visit, day 0 (15, 30, 60 minutes after begining of drug administration and 1, 2, 4, 8, 12 hours after begining of drug administration) and days 1, 2 and 3

• CD4+ and CD8+ T (CD38+ and HLA DR+ positive) cell level

  Baseline visit, day 1 and day 3

• Episomal DNA with 2 LTRs level

  Baseline visit, day 1 and day 3

• Adverse Events

  From baseline visit to day 28 after drug administration

Study Arms (3)

Group 1

PLACEBO COMPARATOR

Patients receiving placebo (sodium chloride) at single dose

Other: Placebo

Group 2

ACTIVE COMPARATOR

Patients receiving Bryostatin 1 (10ug/m2) at single dose

Drug: Bryostatin 1 (10ug/m2)

Group 3

ACTIVE COMPARATOR

Patients receiving Bryostatin 1 (20ug/m2) at single dose

Drug: Bryostatin 1 (20ug/m2)

Interventions

Placebo OTHER

Group 1: Placebo (sodium chloride 0.8 %) at single dose

Group 1

Bryostatin 1 (10ug/m2) DRUG

Group 2: Bryostatin 1 (10ug/m2) at single dose

Group 2

Bryostatin 1 (20ug/m2) DRUG

Group 3: Bryostatin 1 (20ug/m2) at single dose

Group 3

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients understanding the trial purpose
• Patients between 18 and 50 years of age
• Patients with chronic HIV-1 infection
• Patients receiving antiretroviral treatment with at least 3 active drugs for at least 2 years
• Undetectable viral load measured by ultra sensitive methods
• CD4+ levels higher than 350 cells/mm3
• Patients committed to use contraceptive methods during the trial and up to 3 months after.

You may not qualify if:

• Previous antiretroviral treatment failure, as any viral load outbreak after having had undetectable HIV-1 load. Low grade, transitory outbreaks (\<200 RNA copies/ml) resolved without treatment modifications are excluded
• Patients planned to interrupt antiretroviral treatment during the trial
• Patients receiving immunosuppressant or immunostimulant drugs, including valproic acid.
• Pregnant women
• Bryostatin-1 hypersensitivity
• Being enrolled in another clinical trial or having participated in another clinical trial in the previous 3 months.

Sponsors & Collaborators

• Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal: lead

Study Sites (1)

Infectious Diseases Service

Madrid, Non US/Canada, 28034, Spain

Location

Related Publications (4)

• Persaud D, Zhou Y, Siliciano JM, Siliciano RF. Latency in human immunodeficiency virus type 1 infection: no easy answers. J Virol. 2003 Feb;77(3):1659-65. doi: 10.1128/jvi.77.3.1659-1665.2003. No abstract available.

  PMID: 12525599 BACKGROUND

• Blankson JN, Gallant JE, Quinn TC, Bartlett JG, Siliciano RF. Loss of HIV-1-specific immunity during treatment interruption in 2 chronically infected patients. JAMA. 2002 Jul 10;288(2):162-4. doi: 10.1001/jama.288.2.162-a. No abstract available.

  PMID: 12095377 BACKGROUND

• Richman DD, Margolis DM, Delaney M, Greene WC, Hazuda D, Pomerantz RJ. The challenge of finding a cure for HIV infection. Science. 2009 Mar 6;323(5919):1304-7. doi: 10.1126/science.1165706.

  PMID: 19265012 BACKGROUND

• Gutierrez C, Serrano-Villar S, Madrid-Elena N, Perez-Elias MJ, Martin ME, Barbas C, Ruiperez J, Munoz E, Munoz-Fernandez MA, Castor T, Moreno S. Bryostatin-1 for latent virus reactivation in HIV-infected patients on antiretroviral therapy. AIDS. 2016 Jun 1;30(9):1385-92. doi: 10.1097/QAD.0000000000001064.

  PMID: 26891037 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

bryostatin 1

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

• Santiago Moreno, MD, PhD

  Hospital Universitario Ramón y Cajal

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2014
• First Posted: October 21, 2014
• Study Start: September 1, 2014
• Primary Completion: January 1, 2015
• Study Completion: December 1, 2015
• Last Updated: December 18, 2015

Record last verified: 2015-12

Locations

ES (1)