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

HIV Infection Clinical Trial

— BRYOLAT  

Official title:

Bryostatin-1 Effect on HIV-1 Latency and Reservoir HIV-1 Infected Patients Receiving Antiretroviral Treatment: Pilot, Controlled, Double Blinded, Dose Searching Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02269605
• Other study ID #: BRYOLAT
• Status: Completed
• Phase: Phase 1
• First received: October 16, 2014
• Last updated: December 17, 2015
• Start date: September 2014
• Est. completion date: December 2015

Study information

• Verified date: December 2015
• Source: Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Hospital Universitario Ramón y Cajal Review BoardSpain: Agencia Española de Medicamentos y Productos Sanitarios (AEMPs)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: December 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infection

Intervention

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

Drug:
• Bryostatin 1 (10ug/m2)
Group 2: Bryostatin 1 (10ug/m2) at single dose
• Bryostatin 1 (20ug/m2)
Group 3: Bryostatin 1 (20ug/m2) at single dose

Locations

Country	Name	City	State
Spain	Infectious Diseases Service	Madrid	Non US/Canada

Sponsors (1)

Lead Sponsor	Collaborator
Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal

Country where clinical trial is conducted

Spain, 

References & Publications (3)

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. — View Citation

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. Review. — View Citation

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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	Yes
Secondary	CD4+ and CD8+ T (CD38+ and HLA DR+ positive) cell level		Baseline visit, day 1 and day 3	Yes
Secondary	Episomal DNA with 2 LTRs level		Baseline visit, day 1 and day 3	No
Secondary	Adverse Events		From baseline visit to day 28 after drug administration	Yes