This is a double-blind, placebo-controlled, parallel group study to compare the effects of STP7 (mavoglurant) vs placebo control on i.v. cocaine's physiological and subjective effects in non-treatment seeking, cocaine-experienced males or females participants between 18 and 59 years of age.
The primary objective of this study is to determine if there are clinically meaningful interactions between oral STP7 (mavoglurant) treatment concurrent with 20 and 40 mg i.v. cocaine infusions by measuring adverse events and cardiovascular responses including heart rate, blood pressure, and electrocardiogram (including corrected QT interval).
The secondary objectives are:
* To evaluate whether administration of STP7 (mavoglurant) alters the pharmacokinetics of cocaine and/or its major metabolite, benzoylecgonine.
* To determine the pharmacokinetic of STP7 (mavoglurant) administered at a dose of 200 mg twice a day.
* To evaluate whether STP7 (mavoglurant) treatment alters the subjective effects of cocaine measured by Visual Analog Scales (VAS) and Brief Substance Craving Scale (BSCS).

Start Date15 Apr 2024

Sponsor / Collaborator

Stalicla SAStartup

[+1]

NCT05203965

/ RecruitingEarly Phase 1IIT

Functional Neuroimaging of Alcoholism Vulnerability: Probing Glutamate and Reward, Using the mGluR5 Inhibitor Mavoglurant

The purpose of this study is to evaluate the role of Mavoglurant in clarifying the neurobiology of alcoholism risk. This is a one-site, randomized, within subjects, counterbalanced double-blind study of a single dose (200mg) of Mavoglurant and placebo.

Start Date17 May 2022

Sponsor / Collaborator

Yale University

[+1]

100 Clinical Results associated with Mavoglurant

100 Translational Medicine associated with Mavoglurant

100 Patents (Medical) associated with Mavoglurant

Literatures (Medical) associated with Mavoglurant

01 Nov 2024·PSYCHOPHARMACOLOGY

The mGlu5 receptor negative allosteric modulator mavoglurant reduces escalated cocaine self-administration in male and female rats

Article

Author: Acri, Jane B ; Vendruscolo, Leandro F ; Vendruscolo, Janaina C M ; Volkow, Nora D ; Whiting, Kimberly E ; Koob, George F

Abstract:

Rationale:

Cocaine use disorder (CUD) is a brain disorder for which there is no Food and Drug Administration-approved pharmacological treatment. Evidence suggests that glutamate and metabotropic glutamate receptor subtype 5 (mGlu5) play critical roles in synaptic plasticity, neuronal development, and psychiatric disorders.

Objective:

In the present study, we tested the hypothesis that the mGlu5 receptor is functionally involved in intravenous cocaine self-administration and assessed the effects of sex and cocaine exposure history.

Methods:

We used a preclinical model of CUD in rats that were allowed long access (LgA; 6 h/day) or short access (ShA; 1 h/day) to intravenous cocaine (750 µg/kg/infusion [0.1 ml]) self-administration. Rats received acute intraperitoneal or oral administration of the mGlu5 receptor negative allosteric modulator mavoglurant (1, 3, and 10 mg/kg) or vehicle.

Results:

Both intraperitoneal and oral mavoglurant administration dose-dependently reduced intravenous cocaine self-administration in the first hour and in the entire 6 h session in rats in the LgA group, with no effect on locomotion. In the ShA group, mavoglurant decreased locomotion but had no effects on cocaine self-administration. We did not observe significant sex × treatment interactions.

Conclusions:

These findings suggest that the mGlu5 receptor is involved in escalated cocaine self-administration. These findings support the development of clinical trials of mavoglurant to evaluate its potential therapeutic benefits for CUD.

27 Aug 2024·ZEITSCHRIFT FUR PHYSIKALISCHE CHEMIE-INTERNATIONAL JOURNAL OF RESEARCH IN PHYSICAL CHEMISTRY & CHEMICAL PHYSICS

Homology modeling and molecular docking study of metabotropic glutamate receptor 5 variant F: an attempt to develop drugs for treating CNS diseases

Author: Ali, Essam A. ; Rashid, Haroon ur ; Khan, Khalid ; Ahmad, Nasir ; Umar, Muhammad Naveed ; Ullah, Riaz ; Gulfam, Naila ; Khan, Sher Wali ; Zahoor, Muhammad

Abstract:

G protein-coupled receptors (GPCRs) constitute the largest protein family involved in signal transduction and are the main targets for drug delivery. The metabotropic glutamate receptors (mGluRs) are class C of GPCRs that contribute to the modulation of glutamatergic neurotransmission which regulates vital physiological processes and is recognized as a potential therapeutic target throughout the central nervous system. Intracellular C-terminal domains of mGluR are the main targets for proteins regulating these receptors and are also involved in alternative splicing, regulation by phosphorylation, and modulatory protein-protein interactions. Class C of GPCRs exist as dimers and is mediated by interactions between the venus tryflap domain and the transmembrane domain. The mGluR5 variant F can be regulated by both positive and negative allosteric modulators that can potentiate or inhibit the endogenous ligand and glutamate, respectively. Moreover, mGluR5 is involved in many disorders including fragile X syndrome/autism spectrum disorder, schizophrenia, anxiety, addiction, chronic pain and epilepsy, etc. The main purpose of current computational work is to determine the 3D structures of the target protein and their active sites to design new drug molecules as potential biochemical agents. The 3D model of the mGluR5 variant F was constructed through homology modeling techniques using MOE and I-TESSER programs. RAMPAGE and ERRATE online servers were used for the 3D structure evaluation and validation. Furthermore, the mGluR5 variant F was docked with 20 mavoglurant derivatives that act as antagonists. Mavoglurant derivatives 3, 4, 6, 10, 13, 18, and 19 showed a maximum of four interactions with the mGluR5 variant F, whereas derivatives 7, 8, 9, 11, 12, 15, 16, 17 and 20 showed a maximum of three interactions with the mGluR5 variant F. The remaining four mavoglurant derivatives expressed two interactions each with mGluR5 variant F. The docking score for these derivatives ranged between −15.55 and −08.210 kcal mol−1 suggesting their strong interactions with the mGluR5 variant F. Their 3D structure and docking study provides a potential base for the synthesis of new drug candidates to treat brain disorders.

01 Mar 2024·The Journal of clinical investigation

Effects of AFQ056 on language learning in fragile X syndrome

Article

Author: Cudkowicz, Merit ; Hagerman, Randi ; Veenstra-VanderWeele, Jeremy ; Harkey, Brittney ; Klingner, Elizabeth ; Berry-Kravis, Elizabeth ; Coffey, Christopher S ; Pearson, Brenda ; Abbeduto, Leonard ; Huff, Trevis ; Tassone, Flora ; Costigan, Michele ; Long, Jeff ; Erickson, Craig A ; Kaufmann, Walter E ; Fedler, Janel ; Staley, Kevin ; Ecklund, Dixie ; Klements, David ; Ethridge, Lauren ; Moshinsky, Michael ; Friedmann, Katherine ; Hoffmann, Anne ; McDuffie, Andrea ; Hessl, David ; Bullard, Lauren

BACKGROUNDFXLEARN, the first-ever large multisite trial of effects of disease-targeted pharmacotherapy on learning, was designed to explore a paradigm for measuring effects of mechanism-targeted treatment in fragile X syndrome (FXS). In FXLEARN, the effects of metabotropic glutamate receptor type 5 (mGluR5) negative allosteric modulator (NAM) AFQ056 on language learning were evaluated in 3- to 6-year-old children with FXS, expected to have more learning plasticity than adults, for whom prior trials of mGluR5 NAMs have failed.METHODSAfter a 4-month single-blind placebo lead-in, participants were randomized 1:1 to AFQ056 or placebo, with 2 months of dose optimization to the maximum tolerated dose, then 6 months of treatment during which a language-learning intervention was implemented for both groups. The primary outcome was a centrally scored videotaped communication measure, the Weighted Communication Scale (WCS). Secondary outcomes were objective performance-based and parent-reported cognitive and language measures.RESULTSFXLEARN enrolled 110 participants, randomized 99, and had 91 who completed the placebo-controlled period. Although both groups made language progress and there were no safety issues, the change in WCS score during the placebo-controlled period was not significantly different between the AFQ056 and placebo-treated groups, nor were there any significant between-group differences in change in any secondary measures.CONCLUSIONDespite the large body of evidence supporting use of mGluR5 NAMs in animal models of FXS, this study suggests that this mechanism of action does not translate into benefit for the human FXS population and that better strategies are needed to determine which mechanisms will translate from preclinical models to humans in genetic neurodevelopmental disorders.TRIAL REGISTRATIONClincalTrials.gov NCT02920892.FUNDING SOURCESNeuroNEXT network NIH grants U01NS096767, U24NS107200, U24NS107209, U01NS077323, U24NS107183, U24NS107168, U24NS107128, U24NS107199, U24NS107198, U24NS107166, U10NS077368, U01NS077366, U24NS107205, U01NS077179, and U01NS077352; NIH grant P50HD103526; and Novartis IIT grant AFQ056X2201T for provision of AFQ056.

News (Medical) associated with Mavoglurant

19 Sep 2024

·www.globenewswire.com

Dr. Paulo Fontoura, MD, PhD, joins STALICLA as Chief Scientific and Clinical Development Advisor

Press Release Dr. Paulo Fontoura, MD, PhD, joins STALICLA as Chief Scientific and Clinical Development Advisor Geneva, Switzerland – September 19, 2024 – STALICLA SA, a Swiss neuro precision biotech company dedicated to developing precision medicine-based treatments for neurodevelopmental disorders, announced today that Dr. Paulo Fontoura will be joining their drug development team as Chief Scientific and Clinical Development Advisor. Dr. Fontoura will work to support STALICLA’s mission to transform the treatment landscape for neurodevelopmental disorders. Lynn Durham, CEO of STALICLA, said: “We are delighted and humbled to welcome Paulo to the STALICLA team. With his unparalleled insight and unique understanding of CNS drug development and neurodevelopmental disorders, he is strengthening STALICLA’s position as a pioneer in precision neuropsychiatry. Paulo’s expertise will be instrumental in helping us achieve our next milestones, notably our entry into two Phase 2 clinical trials in subgroups of patients with autism spectrum disorder (ASD), each with expected readouts in the coming 24 months.” Dr. Paulo Fontoura is a pioneer in innovative clinical development strategies. During his 16-year tenure at Roche, he served as the Global Head of Neuroscience Clinical Development; he was instrumental in the launch of several groundbreaking medications targeting neurological conditions, including Multiple Sclerosis (MS), Spinal Muscular Atrophy (SMA), and Neuromyelitis Optica Spectrum Disorder (NMOSD), as well as pioneering work on Alzheimer's, Parkinson's, Huntington's disease, and several psychiatric and neurodevelopmental disorders. Specifically, he and his team spearheaded the clinical development of new therapies for Fragile X, Down's and Angelman's syndromes, and the first pharmacological treatment for core symptoms of ASD which reached Phase 3 clinical trials in both adults and children. Additionally, his team co-led the Autism Innovative Medicine Studies (AIMS) including EU-AIMS and AIMS-2-TRIALS public private partnership. Dr. Fontoura has also had an illustrious academic career. He held multiple faculty positions at the New University of Lisbon and Stanford University, where he earned his MD and a PhD in Neuroimmunology and trained as a clinical neurologist. In recognition of his exceptional achievements in the field of neuroscience, he was elected as a Fellow of the American Academy of Neurology in 2022. He currently serves as a visiting professor at the New University of Lisbon and lectures at the European Center of Pharmaceutical Medicine in Basel. Paulo Fontoura MD, PhD, Chief Scientific and Clinical Development Advisor, said: “I am thrilled to join the STALICLA team and help them develop therapies for people with neurodevelopmental disorders. Their approach promises to bring real breakthroughs in this area of great medical need.” About STALICLA: STALICLA SA is a Swiss clinical-stage biopharmaceutical company, revolutionizing the treatment of neurodevelopmental disorders. The company has developed a clinically validated neuro precision development platform, successfully delivering stratified patient subgroups and advancing tailored treatment options. Its lead NDD asset, STP1, and a second NDD asset are set to enter Phase 2 trials with expected readouts within 24 months. STP7 (Mavoglurant), is also being advanced for Phase 3 trials, fully funded by the US government. For more information, please visit: www.stalicla.com. Contacts: STALICLA SALynn Durham Founder & Chief Executive Officerlynn.durham@stalicla.com Media & InvestorsChris MaggosCohesion Bureauchris.maggos@cohesionbureau.com+41 79 367 6254 Attachment 20240918 Paulo Fontoura PR_final

Phase 2Phase 3Executive Change

28 Jun 2024

·www.globenewswire.com

STALICLA publishes pioneering phase 1b data on precision treatment for autism spectrum disorder in Biomedicines

STALICLA’s precision psychiatry study highlights strong EEG-based target engagement of STP1 treatment in defined subgroup of patients with autism and numerical improvement in core symptoms June 27, 2024 – STALICLA SA, a Swiss neuro precision biotech company dedicated to developing precision medicine-based treatments for neuropsychiatric and neurodevelopmental disorders, today announced the publication of a landmark phase 1b study with STP1, a novel combination therapy tailored for the treatment of a clinically and biologically defined subgroup of patients with autism spectrum disorder (ASD), named ASD Phenotype 1 (ASD-Phen1). The results of the study were published in the peer-reviewed journal Biomedicines, in an article titled “Safety, Tolerability, and EEG-Based Target Engagement of STP1 (PDE3,4 Inhibitor and NKCC1 Antagonist) in a Randomized Clinical Trial in a Subgroup of Patients with ASD”. Lynn Durham, CEO of STALICLA, highlighted: “This study marks a significant milestone in the advancement of precision medicine for ASD. It is a first-of-its-kind stratification-based approach for clinical development in neurodevelopmental disorders, demonstrating the potential of precision medicine in ASD.” The randomized, double-blind, placebo-controlled phase 1b clinical trial evaluated the safety and tolerability of STP1, a combination of ibudilast and bumetanide, in ASD-Phen1 patients. The clinical trial (registered at clinicaltrials.gov NCT04644003), involved two 14-day treatment phases of ASD-Phen1 patients receiving STP1 or placebo. The results showed that STP1 was well-tolerated with no significant adverse effects reported. Significant and dose-related reductions in gamma power were observed in the whole brains of patients taking STP1, particularly in regions associated with executive function and memory. Additionally, STP1 increased alpha 2 power in frontal and occipital regions, while improving habituation and neural synchronization to auditory chirps. Dr. Craig A. Erickson, Associate Professor, UC Department of Psychiatry and Behavioral Neuroscience, Cincinnati Children’s Hospital Medical Center, and the principal investigator of the study, remarked: “The electrophysiological signals from this study are remarkable and represent the strongest early trial target engagement signals our lab has seen in the autism field.” Dr. Laura Pérez-Cano, Head of Discovery at STALICLA and co-author of the study, added: “These findings not only highlight the potential of STP1 as a therapeutic option for ASD-Phen1 patients but also underscore the importance of combining biologically-based patient stratification with quantifiable outcome measures such as EEG that can then be correlated with behavioral measures.” By focusing on a biologically defined subgroup of ASD patients, STALICLA is moving closer to making personalized treatment options a reality for patients with ASD. This approach has the potential to revolutionize the treatment of ASD and other neuropsychiatric conditions. STALICLA is a global, clinical-stage biotechnology company focused on advancing precision medicine for brain disorders. The company has developed a unique neuro precision development platform, DEPI, supported by clinical validation in a first indication: Autism Spectrum Disorder. Its lead neurodevelopmental disorder asset, STP1, is entering Phase 2 trials. Its lead neuropsychiatry asset, STP7 (Mavoglurant), fully funded by the US government, will soon be Phase 3 ready for Cocaine Use Disorder. ‎ The content above comes from the network. if any infringement, please contact us to modify.

Clinical Result

08 May 2024

·www.globenewswire.com

STALICLA initiates U.S. Phase 3 enabling DDI study of STP7 (Mavoglurant) to treat cocaine use disorder

May 2, 2024 – STALICLA SA, a late-stage biotechnology company specializing in precision medicine for brain disorders, announces the First Patient First Visit (FPFV) for the company's drug-drug interaction (DDI) study of STP7 (Mavoglurant), an mGluR5 negative allosteric modulator, licensed to STALICLA by Novartis. The DDI study is the last regulatory requirement in a comprehensive Phase 2 program and completion is expected to trigger initiation of a Phase 3 study in the U.S. in 2025. Lynn Durham, CEO and Founder of STALICLA said, “This DDI study unlocks the opportunity under our Cooperative Research and Development Agreement with the U.S. NIH National Institute of Drug Abuse (NIDA) to begin Phase 3 trials for STP7 in 2025 to address the high unmet medical need of cocaine abuse globally. Results from successfully completed Phase 2 studies for cocaine use disorder (CUD) showed highly convincing and unprecedented efficacy results including increase in abstinence from cocaine use and reduction in co-morbid dependencies such as alcohol abuse with STP7 (Mavoglurant). In addition, STALICLA is investigating alternative therapeutic indications for STP7 (Mavoglurant) to benefit patients with other CNS conditions.” STP7 (Mavoglurant) is the most clinically advanced negative allosteric modulator of the glutamate receptor 5 (mGluR5 NAM). As well as its role in addiction pathophysiology, mGluR5 has been implicated in mood disorders and neurodevelopmental disorders such as Fragile X and autism spectrum disorder. Comprehensive clinical studies by Novartis of STP7 (Mavoglurant) to date have included over 1800 adults for up to 2 years, demonstrating good safety and tolerability and significant reduction in cocaine use and positioning STP7 (Mavoglurant) as a strong candidate therapy for substance use and other CNS disorders. STALICLA SA is a Swiss clinical-stage biopharmaceutical company, pioneering precision treatment in neurodevelopmental and neuropsychiatric disorders. Its AI-driven precision neuro medicine platform has allowed to identify two precision small molecule drug candidates for autism spectrum disorder, STP1 and STP2, both planned to enter Phase 2 trials in 2024. Following the in-licensing of Mavoglurant from Novartis in 2023, STALICLA has also established an advanced mGluR5 NAM platform offering multi-faceted late-stage clinical development opportunities broadening STALICLA’s scope to address wider CNS disease unmet needs. For more information, please visit: www.stalicla.com. The content above comes from the network. if any infringement, please contact us to modify.

Phase 3Clinical Result

100 Deals associated with Mavoglurant

External Link

KEGG	Wiki	ATC	Drug Bank
-	Mavoglurant	-	DB13004

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Substance Abuse	Phase 3	United States	National Institute on Drug Abuse	08 Mar 2023
Substance Abuse	Phase 3	United States	Stalicla SAStartup	08 Mar 2023
Fragile X Syndrome	Phase 3	United States	Novartis Pharmaceuticals Corp.	01 Nov 2011
Fragile X Syndrome	Phase 3	Australia	Novartis Pharmaceuticals Corp.	01 Nov 2011
Fragile X Syndrome	Phase 3	Belgium	Novartis Pharmaceuticals Corp.	01 Nov 2011
Fragile X Syndrome	Phase 3	Denmark	Novartis Pharmaceuticals Corp.	01 Nov 2011
Fragile X Syndrome	Phase 3	France	Novartis Pharmaceuticals Corp.	01 Nov 2011
Fragile X Syndrome	Phase 3	Germany	Novartis Pharmaceuticals Corp.	01 Nov 2011
Fragile X Syndrome	Phase 3	Israel	Novartis Pharmaceuticals Corp.	01 Nov 2011
Fragile X Syndrome	Phase 3	Italy	Novartis Pharmaceuticals Corp.	01 Nov 2011

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03327792 (CTgov)	Phase 1	Psychedelic	34	Mavoglurant (200 mg Mavoglurant)	hzxpjxofku = wwiugjfcwi iblzkyalwf (lmlcuwryxa, lolkmfxedq - dffkmbarcg) View more	-	06 Aug 2024
				Placebo (Placebo)	hzxpjxofku = rrtvsznvja iblzkyalwf (lmlcuwryxa, uirzetujso - wsatogqawp) View more
NCT02920892 (FX-LEARN, CTgov)	Phase 2	Fragile X Syndrome	110	placebo+AFQ056 (Placebo Comparator: Double-Blind Placebo With Language Intervention)	ixvrjmviws(yggqbmdmgh) = kssmbyzkcz zambzdhdef (hsxkbloxdw, wihlyxlalu - jeikwrfpgu) View more	-	10 Oct 2023
				AFQ056 (Experimental: Double-Blind AFQ056 With Language Intervention)	ixvrjmviws(yggqbmdmgh) = anbklxxvnl zambzdhdef (hsxkbloxdw, ogonkoxwkr - eqlxohvwfk) View more
NCT03242928 (CTgov)	Phase 2	Cocaine-Related Disorders \| Systemic Carnitine Deficiency	68	AFQ056 (AFQ056)	ymyutqvnow(gmyhilagjq) = xlieshunyo izstonoxha (ijryoxkust, 0.027) View more	-	04 Feb 2021
				Placebo (Placebo)	ymyutqvnow(gmyhilagjq) = aqxoatzjvc izstonoxha (ijryoxkust, 0.024) View more
WPC2019	Not Applicable	-	485	Mavoglurant (AFQ056)	jbjdlxqxxz(qnxuagfkhk) = ypojxelnjj fmibkswomh (tnkiwalrae, -0.65 to 0.11) View more	Negative	03 Jun 2019
				Placebo	jbjdlxqxxz(qnxuagfkhk) = ijkfxufqxz fmibkswomh (tnkiwalrae, -0.09 to 0.66) View more
NCT01348087 (Pubmed \| Sci Rep) Manual	Phase 2	Fragile X Syndrome	267	mavoglurant	owpidnbqwn(fcnhuzkzzi) = wpdrkumpry acnvdneuvs (jzzjlpxqrd ) View more	Negative	19 Nov 2018
NCT01813019 (Pubmed \| Adv Ther) Manual	Phase 2	Obsessive-Compulsive Disorder	50	mavoglurant	bepmuqdxgr(ieapnlhplg) = dtbuhqvqza ckxfwjstvw (swzodfgedk ) View more	Negative	01 Feb 2017
				Placebo	bepmuqdxgr(ieapnlhplg) = zvwxufzrrz ckxfwjstvw (swzodfgedk ) View more
NCT01813019 (CTgov)	Phase 2	Obsessive-Compulsive Disorder	50	Placebo (Placebo)	zuyjkhsvam(gobuprmsip) = vxxpbvcwci taklyvtrxr (xufkxxxwfq, 1.78) View more	-	21 Jul 2016
				AFQ056 (AFQ056)	zuyjkhsvam(gobuprmsip) = vtgcivvnqz taklyvtrxr (xufkxxxwfq, 1.75) View more
NCT01385592 (Pubmed) Manual	Phase 2	Dyskinesia, Drug-Induced \| Parkinson Disease	-	Mavoglurant	xelipoorhg(yerdksvzpj) = did not reach statistical significance noazfuxpxx (whdfakaiab )	Negative	01 Jul 2016
				Placebo
NCT01253629 (Pubmed \| Sci Transl Med) Manual	Phase 2	Fragile X Syndrome	314	Mavoglurant	ldzpangriz(fbgisgwqrq) = Neither of the studies achieved hedalyjypq (ztvfinqtjz )	Negative	13 Jan 2016
				Placebo
NCT01357239 (CTgov)	Phase 2	Fragile X Syndrome	139	Placebo	uubganyhav(drlovbqrwn) = eqyjnvgbkc fykxjmjkvy (dxfamrvqtu, 3.88) View more	-	12 May 2015

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