A Study to Explore the Effect of Sepranolone in Tourette Syndrome

A Randomized, Open-label, Multicenter, Phase 2 Clinical Trial to Explore the Safety and Efficacy of Sepranolone in Pediatric and Adult Patients With Tourette Syndrome

The study was an open-label, randomized, multicenter, parallel, Phase 2a study in adolescents and adult patients with Tourette syndrome that aimed to explore the efficacy of Sepranolone as a treatment for Tourette syndrome, by reducing the severity and frequency of tics. The total study duration from the Screening Visit to the final follow-up visit was approximately 26 weeks and included the following periods:

• A baseline period of 4 weeks between the screening visit (Visit 1) and randomization (4 weeks of baseline period were not needed in well-known adult subjects with stable Tourette syndrome history over the past at least 4 weeks). A school holiday/annual leave period of 2-6 weeks where no study-related activities were done.
• A randomized treatment period of 12 weeks
• A safety follow-up period of 4 weeks

Study Overview

• Status: Completed
• Conditions: Tourette Syndrome; Tourette Syndrome in Adolescence
• Intervention / Treatment: Drug: Sepranolone

Detailed Description

30 subjects aged 12 to 45 years of age diagnosed with Tourette Syndrome with a YGTSS score > 20 during 30 days of baseline observation to be randomized to

1. continued present stable treatment (10 subjects) or
2. continued present stable treatment plus 10 mg of Sepranolone injected s.c. twice weekly for 12 weeks (20 patients) followed by one month of observation

Primary objective: to investigate the efficacy of Sepranolone to reduce tic severity in patients with Tourette Syndrome after 12 weeks of treatment with Sepranolone Change from baseline YGTSS total score at week 4, 8 and 12

Secondary objectives:

1. to investigate the efficacy of Sepranolone to reduce tic related impairment in patients with Tourette Syndrome after 12 weeks of treatment with Sepranolone Change from baseline YGTSS impairment score at week 4, 8 and 12
2. to investigate the efficacy of Sepranolone to reduce the urge to tic in patients with Tourette Syndrome at week 12 of treatment with Sepranolone Change from baseline PUTS score at weeks 4, 8 and 12
3. To evaluate the effect of Sepranolone on activities of daily living in patient with Tourette Syndrome at week 12 of treatment with Sepranolone Change Quality of Life (GTSQOL) physical/activities of daily living subscale at weeks 4, 8 and 12
4. To evaluate the effect on Global impression by Sepranolone at week 12 of treatment with Sepranolone Change from baseline in the Tourette Syndrome - Clinical Global Impression (TS-CGI) score at week 4, 8 and 12

Safety objectives:

to evaluate the safety and tolerability of Sepranolone in patients with Tourette Syndrome

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Peter Nordkild, MD; Phone Number: +4525471646; Email: peter.nordkild@asarinapharma.com

Study Locations

• Denmark
  • Copenhagen, Denmark, 2400
    • Bispebjerg Hospital
  • Herlev
    • Copenhagen, Herlev, Denmark, 2730
      • Herlev Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 55 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Tic severity score ≥ 20 Yale Global Tic Severity Scale (YGTSS) Total Score at baseline
• The patient may have Obsessive-Compulsive Disease (OCD) as a comorbidity

Exclusion Criteria:

• Patient has participated in a clinical study over the past 30 days
• Evidence or history of neurological disease that may interfere with the study
• Malignant disease
• Unstable or clinical significant medical condition that could pose a risk
• HIV/ongoing hepatitis
• Clinical significant findings in vital signs
• History of anaphylactic reactions

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sepranolone; Sepranolone 10 mg sc twice weekly for 12 weeks alongside the patient's standard of care Tourette treatment.	Drug: Sepranolone; Treatment with 10 mg Sepranolone s.c. twice weekly for 12 weeks alongside patient's standard of care Tourette treatment.; Other Names: Isoallopregnanolone
No Intervention: No Intervention; Continuation of the patient's standard of care Tourette treatment for 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To investigate the efficacy of Sepranolone to reduce tic severity in patients with Tourette syndrome at 12 weeks, as measured by change in baseline in the The Yale Global Tic Severity Scale (YGTSS) Total Score.	The Yale Global Tic Severity Scale (YGTSS) is a validated scale for assessing the severity of motor and vocal tics in both children and adults with Tourette syndrome. Tics are scored based on a semi-structured interview, including scoring of the number, frequency, intensity, complexity, and interference of tics. The primary endpoint is the total tic score assessment. The score ranges from 0-50, where a higher score indicates a worse outcome.	Change from baseline at week 4, 8 and 12.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of Sepranolone in adolescent and adult patients with Tourette syndrome	Collection of adverse events (AEs) including spontaneous reporting, number of subjects with clinically significant changes in clinical safety laboratory blood and urine test values, vital signs, weight, and injection related events.	From randomization (day 1) until the end of study visit (week 16).
To evaluate the efficacy of Sepranolone to reduce tic related impairment in patients with Tourette syndrome at 12 weeks, as measured by change in baseline in the Yale Global Tic Severity Scale (YGTSS) Impairment Score.	The Yale Global Tic Severity Scale (YGTSS) is a validated scale for assessing the severity of motor and vocal tics in both children and adults with Tourette syndrome. Tics are scored based on a semi-structured interview, including scoring of the number, frequency, intensity, complexity, and interference of tics. The secondary endpoint is the impairment score assessment. The score ranges from 0-50, where a higher score indicates a worse outcome.	Change from baseline at week 4, 8 and 12.
To evaluate the efficacy of Sepranolone to reduce the urge to tic in patients with Tourette syndrome at 12 weeks, as measured by change in baseline in the Premonitory Urge for Tics Scale (PUTS) scale.	The Premonitory Urge for Tics Scale (PUTS) scale is an assessment aiming to quantify the premonitory urge to tic. The scale is reliable and valid instrument for children from above the age of 10 and for adults. This scale is used as a self-report assessment instrument, where the Investigator asks 10 questions, out of which the score for the first 9 questions add up to the total score (i.e., the 9-Item Total). The respondent has 4 alternatives, "not at all true", "a little true", "pretty much true" and "very much true," represented by a score or 1-4, respectively. The total score ranges from 9-36, where a higher score indicates a worse outcome.	Change from baseline at week 4, 8 and 12.
To evaluate the effect of Sepranolone on activities of daily living in patients with Tourette syndrome at 12 weeks, as measured by change in baseline in the GTS-QoL ADL subscale.	The Gilles de la Tourette Syndrome - Quality of Life (GTS-QoL) physical/activities of daily living (ADL) subscale assesses the impact of the symptoms of Tourette syndrome on the subject's quality of life. The instrument consists of 27 questions, asked by an interviewer, where subjects score the extent of impact on a 5-point verbal scale ranging from "no problems" to "extreme problems." The score ranges from 27-135, where a higher score indicates a worse outcome.	Change from baseline at week 4, 8 and 12.
To evaluate the effect on Global impression by Sepranolone in patients with Tourette syndrome at 12 weeks, as measured by the Tourette Syndrome-Clinical Global Impression (TS-CGI).	The Tourette Syndrome-Clinical Global Impression (TS-CGI) is a clinician rating of the change in severity of the symptoms of Tourette syndrome. The scale is a 7-step Likert scale, where the following alternatives are represented by a score of 1-7, respectively: "very much worsened," "much worsened," "minimally worsened," "no change," "minimally improved," "much improved," or "very much improved." The score ranges from 1-7, where a higher score indicates a better outcome.	TS-CGI score at week 4, 8 and 12.

Collaborators and Investigators

• Sponsor: Asarina Pharma
• Collaborators: Herlev Hospital
• Investigators: Principal Investigator: Nanette Debes, MD, Copenhagen University Hospital at Herlev

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2022
• Primary Completion (Actual): February 1, 2023
• Study Completion (Actual): February 1, 2023

Study Registration Dates

• First Submitted: March 12, 2022
• First Submitted That Met QC Criteria: June 26, 2022
• First Posted (Actual): June 28, 2022

Study Record Updates

• Last Update Posted (Actual): June 9, 2023
• Last Update Submitted That Met QC Criteria: June 7, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Tourette Syndrome in Adults
• 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; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics; Pregnanolone
• Other Study ID Numbers: APH205

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