Date: 2017-05-23
Type of
information: Results
phase: 2
Announcement: results
Company: Neurocrine Biosciences (USA - CA)
Product: Ingrezza® (valbenazine - NBI-98854)
Action
mechanism:
- VMAT2 inhibitor/vesicular monoamine transporter 2 inhibitor. VMAT2 (Vesicular monoamine transporter 2) is a protein concentrated in the human brain that is primarily responsible for re-packaging and transporting monoamines (dopamine, norepinephrine, serotonin, and histamine) in pre-synaptic neurons.
- Valbenazine (NBI-98854) is a potent, highly selective, VMAT2 inhibitor that modulates dopamine release during nerve communication, while at the same time having minimal impact on the other monoamines, thereby reducing the likelihood of "off-target" side effects.
- Modulation of neuronal dopamine levels in diseases such as tardive dyskinesia, Tourette syndrome, Huntington's chorea, schizophrenia, and tardive dystonia, which are characterized, in part, by a hyperdopaminergic state, should provide symptomatic benefits for patients with these diseases.
- Neurocrine has received Breakthrough Therapy Designation from the FDA for valbenazine in the treatment of tardive dyskinesia.
Disease: Tourette syndrome
Therapeutic
area: Rare diseases - Neurological diseases
Country:
Trial
details:
- The T-Force GREEN and T-Forward studies are ongoing multicenter, randomized, double-blind, placebo-controlled, multi-dose, parallel group, Phase II studies to evaluate the safety, tolerability and efficacy of valbenazine. Once-daily fixed doses of NBI-98854 are being evaluated vs. placebo in a 1:1:1 randomization. These studies will each enroll up to 90 patients with moderate to severe Tourette syndrome, the T-Force GREEN is enrolling children and adolescents and the T-Forward is enrolling adults. The primary endpoint of each of these studies is the change from baseline of the Yale Global Tic Severity Scale between placebo and active treatment groups at the end of placebo-controlled treatment. Tourette symptoms will also be evaluated via the Rush Video-Based Tic Rating Scale, Premonitory Urge for Tics Scale as well as Clinical Global Impression scales, among others.
- The long-term phase II study is an open-label, fixed-dose study to evaluate the safety and tolerability of NBI-98854 in up to 180 patients with Tourette syndrome. The study will enroll up to 90 pediatric patients and 90 adult patients with moderate to severe Tourette syndrome. Enrollment in this study is restricted to subjects who have completed either the T-Force GREEN or T-Forward Phase II studies. Evaluation of subjects in the study consists of up to three weeks of screening followed by twenty-four weeks of dosing, then followed by four weeks off-drug at approximately 60 study centers in the United States. Once-daily fixed doses of valbenazine will be evaluated for safety and tolerability via standard clinical laboratory tests, monthly physician examinations and safety scale assessments. The dosing regimen for this study is consistent with the two ongoing Phase II studies; T-Force GREEN and T-Forward. During the study, the symptoms of Tourette syndrome will be evaluated utilizing the Yale Global Tic Severity Scale, the Rush Video-Based Tic Rating Scale, Premonitory Urge for Tics Scale as well as Clinical Global Impression scales.
Latest
news:
- • On May 23, 2017, Neurocrine Biosciences announced that the initial Phase II Tourette syndrome T-Force GREEN study of Ingrezza®(valbenazine) did not meet its primary endpoint. The pre-specified primary endpoint was the change-from-baseline between the placebo and active groups in the Yale Global Tic Severity Scale (YGTSS) at Week 6 in the intent-to-treat (ITT) population.
- Exposure-response analysis showed that the selected doses for this placebo-controlled Phase II study were below the therapeutic range for adequate tic reduction in the majority of pediatric subjects. For the subset of subjects with pharmaceutical exposure in the appropriate range, there was a substantial reduction in tics (e.g., -11.3 to -13.7 points on the YGTSS). For subjects with sub-therapeutic exposure, tic reduction was comparable to placebo (e.g., -4.7 to -8.3 points on the YGTSS). In this study, adverse events were consistent with those observed in previous Ingrezza® studies. There were a total of four discontinuations due to adverse events, two in each of the placebo and Ingrezza® arms.
- Neurocrine Biosciences is also conducting an open-label, fixed-dose study of Ingrezza® in up to 180 subjects with Tourette syndrome. This study has recently completed enrollment.
- • On January 17, 2017, Neurocrine Biosciences announced results from the Company's Phase II T-Forward study of Ingrezza® (valbenazine) in adults with Tourette syndrome. While the study showed a significant improvement in overall symptoms of Tourette syndrome as evidenced by the Clinical Global Impression of Change (p=0.015), the pre-specified primary endpoint, the change-from-baseline in the Yale Global Tic Severity Scale (YGTSS) at Week 8 was not met (p=0.18). Adverse events were dose dependent and consistent with earlier clinical studies. Ingrezza® is now looking forward to the pediatric study readout next quarter.
- • On July 28, 2016, Neurocrine Biosciences announced that it has initiated a Phase II clinical trial for NBI-98854 (valbenazine) in children, adolescents and adults with Tourette syndrome. This study is an open-label, fixed-dose, study of up to 180 male and female patients with Tourette syndrome, consisting of up to 90 children and adolescents and up to 90 adults. The primary purpose of the study is to assess the long-term safety and tolerability of valbenazine. Enrollment in this long-term study is limited to subjects who have completed either the ongoing placebo-controlled T-Force GREEN or T-Forward studies. Patients will receive once-daily dosing during a twenty-four week treatment period to assess the safety and tolerability of valbenazine.
- • On February 2, 2016, Neurocrine Biosciences announced that it has initiated a Phase II clinical trial for NBI-98854 (valbenazine) in children and adolescents with Tourette syndrome. The T-Force GREEN study is a randomized, double-blind, placebo-controlled, multi-dose, parallel group, study of up to 90 children and adolescents. Subjects will receive once-daily dosing of valbenazine during a six-week treatment period to assess the safety, tolerability and efficacy of valbenazine in pediatric Tourette patients. The primary endpoint of this study is the change from baseline of the Yale Global Tic Severity Scale between placebo and active treatment groups at the end of week six. Data readout from this study is expected later in 2016.
Is
general: Yes
