Date: 2014-11-17
Type of information: Results
phase: 1- 2
Announcement: results
Company: Bionor Pharma (Norway) Celgene (USA - NJ)
Product: Vacc-4x + Revlimid® (lenalidomide)
Action
mechanism: peptide/immunotherapy product/immunomodulating agent. Vacc-4x is a therapeutic HIV-vaccine based on four, slightly modified peptides (building blocks of proteins) from conserved parts of the HIV-virus. Endocine is an adjuvant shown to enhance the immune response to vaccine antigens delivered nasally.
This investigational HIV vaccine Vacc-4x has already completed a large exploratory phase II randomized, multinational (USA and 4 European countries), double-blind, placebo-controlled trial. It has shown that patients achieved a statistical significantly lower viral load compared to the placebo group.
Disease: HIV-1 infection
Therapeutic area: Infectious diseases
Country: Germany
Trial
details: The Phase I/II trial was an exploratory double-blind placebo controlled immunogenicity study of Vacc-4x + Revlimid (lenalidomide) versus Vacc-4x with an initial open label dose escalation assessment of lenalidomide in HIV infected subjects on antiretroviral therapy, ART (SOC HIV treatment). Part A, the Phase I part of the trial, was an open label dose escalation assessment of lenalidomide, showed that all three doses tested were well tolerated, and the highest dose has been chosen for Part B of the study. Part B was a double-blinded placebo controlled parallel design, multicenter study. Both parts were in HIV infected subjects who are on ART but have not fully regained a healthy CD4 level (CD4 counts > 200x106/mL and < 500x106/mL. The trial was conducted in four centers in Germany. The primary objective of this study is in Part A to establish the maximum tolerated dose of lenalidomide and in Part B to evaluate the immunomodulatory effect of lenalidomide under immunization with Vacc-4x (Vacc-4x + lenalidomide versus Vacc-4x + placebo) on CD4 counts, T-cell response to Vacc-4x and assessment of antibody titer to Vacc-4x peptides and p24, and four vaccine peptides to a non-HIV vaccine antigen (tetanus toxoid antibody titer) as measured from week 21 to week 26. Study period for part B, Phase II of the trial, was 26 weeks (13 weeks immunization period + 13 weeks follow-up). Twenty four patients were randomized into two groups where one group received Vacc-4x + placebo and one group received Vacc-4x + Revlimid. Patients received six cycles of Vacc-4x vaccination with Revlimid or placebo over a 13 week period. Key endpoints were observed at week 13 and at week 26 (study end). During treatment period all patients remained on ART and received six immunizations (four primary immunizations and two booster immunizations) at weeks 1,2 3 and 4 and booster immunizations at weeks 12 and 13 with either Vacc-4x +lenalidomide or placebo over a 13 week period. Key endpoints were observed at week 13 and at week 26 (study end). The patients received lenalidomide or placebo two days prior and on each day of vaccination.(NCT01704781)
Latest
news: * On November 17, 2014, Bionor Pharma announced the results from the Vacc-4x + Revlimid® (lenalidomide) study also known as the “Boost & Kill” study. The Phase II trial was an exploratory double-blind placebo controlled immunogenicity study of Vacc-4x + Revlimid versus Vacc-4x in HIV subjects on ART (HIV standard of care treatment). •Treatment with Vacc-4x + Revlimid (lenalidomide) was well tolerated The study’s principal objective was to assess the combination of Vacc-4x + Revlimid in people living with HIV on ART but who have not regained a healthy CD4 level. Twenty four patients were randomized into two groups where one group received Vacc-4x + placebo and one group received Vacc-4x + Revlimid. Patients received six cycles of Vacc-4x vaccination with Revlimid or placebo over a 13 week period. Key endpoints were observed at week 13 and at week 26 (study end). CD4 counts, the key primary efficacy endpoint increased in both groups. The largest increase was in the Vacc-4x + Revlimid group where CD4 count increased by 30% (p=0.009) from baseline. In the Vacc-4x + placebo group the CD4 count increased with 17% (p=0.10). However, this was an exploratory study, with a limited number of patients and no statistical difference was observed between the two groups. The three other primary endpoints investigating immune response were T-cell response to Vacc-4x, antibody titer to Vacc-4x peptides and p24, and assessment of antibody titers to a commonly used tetanus toxoid. These immune markers supported the quantitative findings of the CD4 cells. Only one serious adverse event was observed and deemed unrelated to treatment and overall both Vacc-4x and the combination treatment of Vacc-4x + Revlimid were well tolerated. Full data analysis is ongoing and will be submitted to a future major HIV medical conference. Furthermore the results will be discussed with FDA and EMA. The study is a collaboration between Celgene Corp (NASDAQ:CELG) and Bionor Pharma. Bionor Pharma has been the study sponsor and Celgene has co-funded the trial and supplied lenalidomide. This study, an important outcome of this collaboration, will be further discussed and analysed by the companies. One serious adverse event reported (SAE) in this study was a case of subcutaneous abscess that appeared 45 days after the patient was vaccinated. The SAE was evaluated and classified as unrelated by study investigators. The overall clinical and laboratory tolerance profile was satisfactory.
•Increase in CD4 count in both treatment groups notably in Vacc-4x + Revlimid group
•Qualitative immune response analyses support the quantitative findings
