In October 2015, the Phase 2 clinical trial results of Validive (clonidine MBT) were announced, demonstrating encouraging signs of clinical activity and safety compared to placebo in decreasing the incidence of severe oral mucositis (SOM) in patients with head and neck cancer (HNC). The trial enrolled 183 patients and was conducted in more than thirty centers in Europe and in the U.S. This global, multi-center, double-blind, randomized, placebo-controlled, three-arm study (NCT01385748) compared the efficacy and safety of two doses of Validive (50 microgram (µg) and 100 µg) to placebo in patients with HNC receiving chemoradiation therapy. Validive and placebo were applied to the gum of the mouth once daily beginning1 to 3 days prior to chemoradiotherapy and continuing until the end of chemoradiotherapy treatment.
The safety profile of Validive was similar to placebo. Patients treated with Validive experienced less nausea and dysphagia compared to placebo.
|Placebo (N=62)||Validive® 50 μg (N=56)||Validive® 100 μg (N=65)||Validive® pooled doses (N=121)|
|Patients experienced at least one TEAE||61 ( 98.4%)||48 ( 87.3%)||60 ( 93.8%)||108 ( 90.8%)|
|Patients experienced at least one TEAE related to the study treatment||18 ( 29.0%)||14 ( 25.5%)||18 ( 28.1%)||32 ( 26.9%)|
|Patients experienced at least one severe TEAE (≥ grade 3) related to study treatment||4 ( 6.5%)||8 ( 14.5%)||4 ( 6.3%)||12 ( 10.1%)|
|Patients permanently removed from the study due to a TEAE||1 ( 1.6%)||3 ( 5.5%)||3 ( 4.7%)||6 ( 5.0%)|
The mean overall patient compliance was approximately 90% across all treatment groups. Overall compliance according to patient diaries was similar in all treatment groups and consistent with the compliance according to the investigator's evaluation.
The analysis of the OPC patients in this study showed:
- The incidence of SOM (primary endpoint) was reduced by 26.3% (40% relative to placebo) in OPC patients treated with Validive (100 μg) (p=0.09 which is a meaningful trend but not statistically significant). 65.2% of OPC patients on placebo experienced severe oral mucositis compared to only 38.9% of OPC patients on Validive 100 µg.)
- Validive (100 µg) reduced the risk of onset of SOM by 52% compared to placebo
- Secondary endpoints of severe drinking, eating, and speaking limitations due to mouth and throat soreness (MTS) score were reduced in the Validive (100 μg) treated cohort
- Decreases in other indicators of clinical benefit including decreased duration of SOM (15 days), decreased weight loss, decreased opiate use and increased cumulative dose of radiation received strongly favored the Validive (100 μg) treated cohort
- A dose response was observed with the Validive (100 μg) dose, demonstrating a trend toward superiority over the Validive (50 μg) dose as well as placebo
The effect of Validive (clonidine MBT) on SOM was much greater in OPC compared to non-OPC patients in this Phase 2 trial. The results of this trial support the further development of Validive for the treatment of SOM in patients with OPC.
Adaptive trial that will evaluate Validive