Clinical Trials

Date: 2017-01-03

Type of information: Presentation of results at a congress

phase: 3

Announcement: presentation of results at the Conference on Retroviruses and Opportunistic Infections (CROI)

Company: TaiMed Biologics (Taiwan) Theratechnologies (Canada)

Product: ibalizumab

Action mechanism: monoclonal antibody. Ibalizumab is a CD4-directed HIV entry-inhibitor and is the first humanized monoclonal antibody in clinical trials for the treatment of HIV. Ibalizumab was designated a Breakthrough Therapy by the FDA based on preliminary clinical evidence indicating that it may represent a substantial improvement over existing therapies on one or more clinically significant endpoints. In a Phase IIb clinical trial, conducted on 113 patients, the product significantly reduced viral load in multi-drug resistant HIV-infected patients. The  FDA has also granted ibalizumab Orphan Drug designation.

Disease: HIV-1 infection

Therapeutic area: Infectious diseases

Country:

Trial details: TMB-301 is a single arm, 24-week study of ibalizumab plus optimized background regimen in treatment experienced patients infected with multi-drug resistant HIV-1. The primary objective of the study is to demonstrate the antiviral activity of ibalizumab 7 days after the first dose of ibalizumab. Patients receiving their current failing ART regimens were monitored during a 7 day control period. Thereafter, a loading dose of 2000 mg of intravenous ibalizumab was the only ART added to their regimen. The primary efficacy endpoint is the proportion of patients achieving a ? 0.5 log10 decrease in HIV-1 RNA 7 days after initiating Ibalizumab therapy, day 14 of the study. Ibalizumab is continued at doses of 800mg IV every two weeks through 24 weeks on study treatment. Safety and additional efficacy endpoints are evaluated during the study. (NCT02475629)

Latest news:

• • On January 17, 2017, Theratechnologies announced that the abstract submitted by its partner, TaiMed Biologics, for the 24-week study results of the ibalizumab (IBA) phase III study (TMB-301) has been selected for a late breaker presentation, Tuesday, February 14th, 2017, at the Conference on Retroviruses and Opportunistic Infections (CROI) to be held in Seattle, WA, from February 13 to 16, 2017. These results were first announced in November 10, 2016 (see below). Dr. Brinda Emu, Assistant Professor of Medicine, Infectious Diseases, Yale School of Medicine, CT, will be presenting additional efficacy and safety data related to the 24-week study. In addition, an abstract presenting the preliminary pharmacokinetics (PK) and pharmacodynamics (PD) data of a study comparing the intramuscular (IM) to the intravenous (IV) administration of ibalizumab has also been accepted for a presentation, Wednesday, February 15, 2017. The results of this study demonstrate that the PK profile of 800 mg IBA bi-weekly IM administration was comparable to the 800 mg IV bi-weekly administration while maintaining effective concentration during the dosing period.
• • On November 10, 2016, Theratechnologies announced that it has been notified by its partner, TaiMed Biologics, of the preliminary results for the safety and efficacy secondary endpoints of the 24-week Phase III trial with ibalizumab in patients with multi-drug resistant (MDR) HIV-1 (TMB-301). This Phase III trial confirms the safety and efficacy results of ibalizumab observed in the previously completed Phase IIb study, despite the fact that the patient population in the Phase III trial had higher levels of MDR HIV-1 and more advanced disease at time of enrollment. In the Phase III trial, after 24 weeks of treatment, the mean reduction in viral load was 1.6 log10 and a total of 48% of patients had a reduction in viral load of more than 2.0 log10 during this period. At the end of the treatment period using ibalizumab with optimized background regimen, the proportion of study participants with undetectable viral load (HIV-1 <50 copies/mL) was 43% (mean viral load reduction of 3.1 log10) and 53% of patients had a viral load lower than 400 copies/mL. The mean viral load of patients at baseline was 100,287 copies/mL. As previously announced, the preliminary results also indicated that 83% of patients enrolled in the Phase III trial (33/40, p<0.0001) have met the primary endpoint of a decrease of ? 0.5 log10 in viral load following a 7-day treatment period with ibalizumab. The safety results in this Phase III trial are consistent with the ones previously observed in the Phase IIb study. Other than for one case of immune reconstitution inflammatory syndrome, an inflammatory response in HIV-infected patients that may be triggered after changing to more active antiretroviral therapy (ART), no serious adverse events (SAEs) were considered to be related to ibalizumab. Most treatment-emergent adverse events reported were mild to moderate in severity. No notable trends in laboratory abnormalities were observed.
• • On May 24, 2016, Theratechnologies announced that it has been notified by its partner, TaiMed Biologics, of the preliminary results for the primary end point of the phase III trial with ibalizumab in patients with multi-drug resistant HIV-1 (TMB-301). Preliminary results indicate that 82.5% of patients enrolled in the phase III study (33/40, p-value <0.0001) have met the primary endpoint of a decrease of ? 0.5 log10 in viral load following a 7-day treatment period with ibalizumab. This result is statistically significantly better than results observed during the control period. The administration of ibalizumab was well tolerated during the first week of treatment. TaiMed plans to submit an abstract to present these results at a major scientific conference later this year. The study should be completed before the end of October 2016.   
•   • On  April 27, 2016, Theratechnologies announced that it has been notified by its partner, TaiMed Biologics that the enrollment for the Phase III study of ibalizumab, in combination with optimized background regimen (patients’ current therapy), for patients infected with multi-drug resistant HIV-1 has been completed as of April 27, 2016. The enrollment in the US has reached 36 patients, exceeding the minimum of 30 patients proposed by the FDA. The last patient enrolled in the study has entered the initial 7-day control period. On Day 7, ibalizumab will be administered and the primary end point will be assessed 7 days after initiation of ibalizumab on Day 14. The study will continue for a total of 24 weeks of treatment with ibalizumab. This open label, single arm Phase III study is the last clinical trial required by the FDA to complete the BLA submission. The primary end point is the proportion of patients achieving a viral load reduction of at least 0.5 log10 at Day 14. Top-line results of the primary end point should be available by the end of May 2016.

 

Is general: Yes