Study of ABX-1431 in Adult Patients With Tourette Syndrome or Chronic Motor Tic Disorder

NCT03625453 | Completed Phase 2

• 2 other identifiers: ABX-1431 PN0182018-000100-41
• Study Type: interventional
• Target: 50
• Locations: 3 countries
• Sites: 8

Brief Summary

Two-part study consisting of a double-blind, randomized, placebo-controlled, study at two target dose levels (Part 1) and an open-label, non-randomized study (Part 2) to determine the efficacy of ABX-1431 in treating adult patients with Tourette syndrome or Chronic Motor Tic Disorder as measured by the change from baseline in Total Tic Score of the Yale Global Tic Severity Scale (YGTSS-TTS) compared with placebo.

Conditions

Tourette Syndrome; Motor Tic Disorder

Keywords

Tourette Syndrome; Chronic Motor Tic Disorder

Outcome Measures

Primary Outcomes (1)

• Change from baseline in Total Tic Score of the Yale Global Tic Severity Scale (YGTSS-TTS) compared with placebo

  The Yale Global Tourette Severity Scale (YGTSS) is a clinician-completed rating scale to capture TS symptom severity. The number, frequency, intensity, complexity, and interference of both motor and vocal tics are rated on an ordinal scale between 0 and 5, with higher scores indicating greater severity. Motor and vocal tics subscales are reported (0 - 25) and then summed for a total tic score (TTS) (0 - 50). The TTS has been used as the registration endpoint for pharmacological therapies. The YGTSS has an Impairment subscale (0 - 50) which is then added for a total global score of 0 - 100.

  Day 56 (40 mg ABX-1431 per day) and Day 28 (20 mg ABX-1431 per day)

Secondary Outcomes (7)

• Adult Tic Questionnaire (ATQ)

  Part 1: days 0, 14, 28, 42, 56; Part 2: days 0, 14, 28

• Premonitory Urge for Tics Scale (PUTS)

  Part 1: days 0, 14, 28, 42, 56; Part 2: days 0, 14, 28

• Clinical Global Impressions Scale for Improvement (CGII)

  Part 1: days 14, 28, 42, 56; Part 2: days 14, 28

• AE occurrence

  Throughout the study: Part 1: day - 30 to day 70; Part 2: day 0 to day 42

• SAE occurrence

  Throughout the study: Part 1: day - 30 to day 70; Part 2: day 0 to day 42

Study Arms (2)

ABX-1431

EXPERIMENTAL

Oral use of hard capsule (10 milligrams), maximum dose per day: 40 milligrams

Drug: ABX-1431

Placebo

PLACEBO COMPARATOR

Oral use of hard capsule

Drug: Placebo

Interventions

ABX-1431 DRUG

Part 1: 8 weeks with daily administration; Patients who choose to enter Part 2: additional 4 weeks with daily administration

ABX-1431

Placebo DRUG

Part 1: 8 weeks with daily administration

Placebo

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patient is a male or female ≥ 18 to 64 years of age at the Screening Visit.
• Patient has a diagnosis of Tourette Syndrome or Chronic Motor Tic Disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria.
• Patient's YGTSS-TTS results must be ≥ 22 (range 0-50) at the Baseline/Randomization Visit.
• Patient is legally competent, has been informed of the nature and scope of relevance for the study, voluntarily agrees to participation, agrees to the study restrictions, and has signed the informed consent form (ICF) approved by the Ethics Review Committee (ERC).
• Patients using cannabinoid medications for their tics must discontinue their use at least 14 days prior to the Baseline/Randomization Visit. The investigator and patient must be confident that these patients will not require these medications for the duration of the study until 14 days after the last dose of study medication. Examples of cannabinoids include cannabis in any form, nabilone or Δ9-tetrahydrocannabinol (THC)-containing medications such as nabiximols (Sativex®) or dronabinol. The use of recreational cannabinoids during this study is not permitted.
• Female patients of child-bearing potential must have a negative pregnancy test \[serum or urine human chorionic gonadotropin (hCG)\] at the Screening Visit and other indicated visits. They must practice a highly effective, reliable, and medically approved contraceptive regimen during the study (e.g., theoretical failure rate less than 1% per year as described in the 2014 Heads of Medicines Agencies: Clinical Trials Facilitation Group report on contraception in clinical trials, which include oral or parenteral or implanted hormonal contraception, vaginal ring releasing hormonal contraception (e.g., Nuvaring, intrauterine device, or intrauterine system). Post-menopausal women may enter this study. Post-menopausal women are defined as those without menses in the past 12 months, and with a serum follicle stimulating hormone (FSH) in the post-menopausal range. Women who are surgically sterile may enter this study with written documentation of the surgical procedure.
• Male patients must be willing to use a condom with sexual partners during this study until 14 days after the last dose of study medication. Male patients must be willing to abstain from sperm donation for 3 months after the completion of this study.

You may not qualify if:

• Patient is taking strong inducers or inhibitors of cytochrome P450 (CYP)3A4/5 or CYP2C9. Examples of strong CYP3A4/5 inducers include carbamazepine, efavirenz, nevirapine, barbiturates, pioglitazone, modafinil, enzalutamide, oxcarbazepine, rifampicin, St. John's Wort (Hypericum perforatum), and phenytoin. Examples of potent CYP3A4/5 inhibitors include atazanavir, boceprevir, clarithromycin, grapefruit juice, indinavir, itraconazole, ketoconazole, nefazodone, suboxone, nelfinavir, posaconazole, ritonavir, saquinavir, telithromycin, and voriconazole. Examples of CYP2C9 strong inducers/inhibitors include carbamazepine, enzalutamide, fluconazole, valproic acid, phenobarbital, nevirapine, rifampicin, and St. John's Wort.
• Patient has evidence of alcohol abuse or dependence, as defined by the DSM-5 criteria, with two or more of the 11 criteria at the Screening Visit or within 1 year before the Screening Visit.
• Patient is unwilling to comply with study restrictions including abstinence from cannabis and alcohol from the Baseline/Randomization Visit until the follow-up telephone call 14 days after the last dose of study medication.
• Patients receiving ongoing psychological therapy for tics such as Habit Reversal Training or Comprehensive Behavioral Intervention for Tics are excluded. Patients who have completed behavioral therapy for tics at least 30 days before the Baseline/Randomization Visit may participate.
• Patient is a lactating or pregnant female, or a female who intends to become pregnant within 90 days following the last dose of study medication.
• Patient has one or more of the following laboratory results at the Screening Visit:
• Aspartate transaminase (AST) \> 3 x upper limit of normal (ULN)
• Alanine transaminase (ALT) \> 3 x ULN
• Total bilirubin \> 2 x ULN (unless due to Gilbert's syndrome)
• Patient has an estimated creatinine clearance less than 60 mL/minute at the Screening Visit. Creatinine clearance (Clcr) is estimated by the Cockcroft-Gault (C-G) equation from a spot serum creatinine (mg/dL) determination using the following formula:
• CLcr (mL/min) = \[140 - age (years)\] × weight (kg) / 72 × serum creatinine (mg/dL)\] × \[0.85 for female patients\]
• Patient has a serum albumin level below the laboratory normal range at the Screening Visit, and the physician cannot rule out hepatic insufficiency based on consideration of clinical symptoms, clinical signs, and other laboratory tests. (The physician may decide that a low value of a serum albumin is clinically insignificant or the test may be repeated.)
• Patient has symptomatic chronic Hepatitis B and/or Hepatitis C Virus infection. Asymptomatic seropositive individuals without clinical or clinical laboratory manifestations of hepatitis may be enrolled.
• Patient has a clinically significant abnormality on the ECG at the Screening Visit.
• Patients with a history of cancer will be excluded, with two exceptions: Patients with a history of squamous or basal cell carcinoma of the skin treated with documented success of curative therapy \> 3 months may be enrolled. Patients with cancer and in remission with no treatment for at least 2 years prior to the Screening Visit may be enrolled.

Sponsors & Collaborators

• Abide Therapeutics: lead
• FGK Clinical Research GmbH: collaborator
• BASi (Bioanalytical Systems, Inc.): collaborator
• CogState Ltd.: collaborator

Study Sites (8)

Charité, Universitätsmedizin Berlin, Klinik für Neurologie mit Experimenteller Neurologie

Berlin, Germany

Location

Uniklinik Köln, Klinik für Psychiatrie und Psychotherapie

Cologne, Germany

Location

Medizinische Hochschule Hannover (MHH), Klinik für Psychiatrie, Sozialpsychiatrie und Psychotherapie

Hanover, Germany

Location

Universität zu Lübeck, CBBM / Institut für Neurogenetik

Lübeck, Germany

Location

LMU Klinikum der Universität München, Klinik für Psychiatrie und Psychotherapie

München, Germany

Location

Centrum Medyczne Damiana Holding Sp zo.o.

Warsaw, Poland

Location

Complejo Hospitalario Regional Virgen Del Rocío

Seville, Andalusia, Spain

Location

Complejo Hospitalario Gregorio Marañón

Madrid, Spain

Location

Related Publications (1)

• Muller-Vahl KR, Fremer C, Beals C, Ivkovic J, Loft H, Schindler C. Monoacylglycerol Lipase Inhibition in Tourette Syndrome: A 12-Week, Randomized, Controlled Study. Mov Disord. 2021 Oct;36(10):2413-2418. doi: 10.1002/mds.28681. Epub 2021 Jun 12.

  PMID: 34117788 DERIVED

MeSH Terms

Conditions

Tourette Syndrome; Tic Disorders

Interventions

ABX-1431

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neurodevelopmental Disorders; Mental Disorders

Study Officials

• Chan Beals, M.D., Ph.D.

  Abide Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, placebo-controlled

Study Record Dates

• First Submitted: August 8, 2018
• First Posted: August 10, 2018
• Study Start: October 15, 2018
• Primary Completion: January 20, 2020
• Study Completion: January 20, 2020
• Last Updated: April 8, 2020

Record last verified: 2020-04

Locations

DE (5); PL (1); ES (2)