Efficacy and Safety of Gemlapodect in Adults and Adolescents With Tourette Syndrome (Allevia2)

A Double-blind, Placebo-controlled, Phase 2b, Multi-center, Twelve-week Prospective Study to Evaluate the Efficacy and Safety of Gemlapodect in Adult and Adolescent Patients With Tourette Syndrome

This study is designed to evaluate the efficacy and safety of gemlapodect (NOE-105) on reducing tics associated with Tourette Syndrome (TS) in adults with TS. Adolescents will be enrolled after a sentinel cohort of adults is complete.

Study Overview

• Status: Not yet recruiting
• Conditions: Tourette Syndrome
• Intervention / Treatment: Drug: Gemlapodect; Drug: Placebo

Detailed Description

Gemlapodect is an investigational selective PDE10A inhibitor with a potential therapeutic effect for the treatment of tics associated with Tourette Syndrome (TS). This is a multi-center, double-blind, parallel-arm, placebo-controlled study in patients with TS. Following screening to confirm eligibility and to wash-out previous TS medication during a 14-day placebo run-in, patients will be randomized 1:1 on Day 1 to receive gemlapodect or placebo once daily for 12 weeks.

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Noema Pharma; Phone Number: please contact via email; Email: clinicaltrials@noemapharma.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Initially, patients aged 18 years onwards, at the time of signing the ICF form. Adolescents aged 12 years and older at the time of signing the ICF/informed assent form will be eligible for inclusion after completion of a sentinel cohort of adults
2. Moderate to severe Tourette Syndrome as defined by DSM-5 diagnostic criteria and TS-CGI-S ≥ 4.
3. Treatment naive or previously treated patients in need of treatment alternative as per investigators judgement.
4. Patients must discontinue all medications used to treat TS for at least 14 days prior to randomization. Other psychotropic drugs, including stimulants, will be allowed provided they have been stable for at least 30 days prior to randomization and are expected to remain stable for the duration of the study.
5. BMI within the range 18 to 35 kg/m2 (inclusive).
6. Women of childbearing potential should only be included after a confirmed menstrual period and a negative highly sensitive urine or serum pregnancy test. Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
7. Capable of giving signed informed consent or consent from their legal representative.
8. Fluency in the language of the investigator, study staff, and the ICF/informed assent form when applicable.

Exclusion Criteria:

1. Any medical condition which, in the opinion of the investigator, could interfere with study procedures including but not limited to functional tic-like disorder, secondary tic symptoms accompanied by late-onset tics, Huntington's chorea, malignant TS, neuroacanthocytosis, mental retardation as defined by the investigator, and autism.
2. Current diagnosis of severe anxiety, bipolar disorder, schizophrenia, or major depressive disorder (MDD). Patients with MDD on selective serotonin reuptake inhibitors treatment stable for greater than or equal to 1 month can participate in the study.
3. A history of severe traumatic brain injury or stroke.
4. Any unstable medical conditions, severe symptoms, or clinically significant abnormalities on screening test/examinations, including uncontrolled seizure disorders, which, in the investigator's judgment, will put them at a risk of major AE during this trial, or will interfere with safety and efficacy assessments.
5. Are undergoing active CBT (including but not limited to comprehensive behavioral intervention for tics, exposure and response prevention, relaxation training) during the last 28 days before the planned date of randomization and until the end of the trial. Patients willing to discontinue their CBT over this period are eligible to the study.
6. Known DSM-5 diagnosis of substance abuse or dependence.
7. Active suicidal ideation or behavior, as assessed by the C-SSRS
8. Use of prescribed or recreational cannabinoids during the study are prohibited. Prescribed cannabinoids include Epidiolex® (cannabidiol), Marinol® /Syndros® (dronabinol), and Cesamet® (nabilone). These medications will be discontinued during the Screening period. Recreational cannabinoids, regardless of their form of intake, which include tetrahydrocannabinol and/or cannabidiol, are prohibited.
9. Strong inhibitors of CYP3A4 are prohibited; commonly used strong inhibitors of CYP3A4 are limited to systemic oral antibiotics (e.g., clarithromycin, telithromycin), systemic, oral antifungals (eg, itraconazole, ketoconazole), and antivirals (eg, atazanavir, darunavir, indinavir).
10. Neurostimulation/deep brain stimulation for TS.
11. Participation in another clinical study with a study intervention administered in the last 30 days.
12. Patients with a known hypersensitivity to gemlapodect or any of the excipients of the product
13. Positive urine drug screen for cannabis, cocaine, or nonprescribed opiates.
14. The person is an employee or family member of an employee of the Sponsor, Investigator, or study site personnel..
15. Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.
16. Previous randomization in the present study.
17. The person is currently committed to an institution by virtue of an order issued either by the judicial or the administrative authorities

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Escalating doses of matching placebo	Drug: Placebo; Administered in the form of oral capsules with inert ingredients.
Experimental: Gemlapodect; Escalating doses of NOE-105 capsules	Drug: Gemlapodect; Gemlapodect is an investigational selective PDE10A inhibitor with a potential therapeutic effect for the treatment of tics associated with TS. Administered in the form of oral capsules.; Other Names: NOE-105

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in tic severity score on the Revised Yale Global Tic Scoring Scale (YGTSS-R)	YGTSS-R is a clinician rated score that evaluates number, frequency, intensity, complexity and interference of motor and phonic tics with a total score ranging from 0 to 50, with 50 being the most severe and 0 being no tics. Change in YGTSS-R total tic scores from baseline (randomization) to D85 for gemlapodect as compared to placebo. The primary estimand is the difference in means between gemlapodect and placebo for the change in the TTS of the YGTSS-R from baseline (randomization) to D85, in the target patient population of adult and adolescent patients with TS, regardless of whether or not dose reduction, suspension, or treatment discontinuation occurred due to events attributable to treatment, and regardless of change in background medication (dose and product) while under treatment, but in the absence of any new treatment started after discontinuation of investigational intervention	85 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Impact on patient functioning	Change in Sheehan Disability Scale from baseline (randomization) to D85 for gemlapodect as compared to placebo	85 days
Change in PUTS	Change in premonitory urge for tics scale from baseline (randomization) to D85 for gemlapodect as compared to placebo	85 days
Safety and Tolerability of gemlapodect	The Incidence and severity of adverse events, including serious adverse events and adverse events of special interest	85 days
Assessment of suicidality and suicidal ideation	Change in Columbia suicide severity rating scale (C-SSRS) subscale from baseline(randomization) to D85 for gemlapodect as compared to placebo. The C-SSRS supports suicide risk assessment through a series of simple, plain-language questions to assesses suicidal ideation and suicidal behavior.	85 days

Collaborators and Investigators

• Sponsor: Noema Pharma AG
• Investigators: Study Director: Clinical Director, MD, Noema Pharma AG

Study record dates

Study Major Dates

• Study Start (Estimated): May 31, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: December 6, 2023
• First Submitted That Met QC Criteria: March 12, 2024
• First Posted (Actual): March 18, 2024

Study Record Updates

• Last Update Posted (Actual): March 18, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Disease; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Neurodevelopmental Disorders; Tic Disorders; Syndrome; Tourette Syndrome
• Other Study ID Numbers: NOE-TTS-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No