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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Noema Pharma AG

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

10 Jul 2024 → 15 Jan 2026

Decision date (initial)

2024-03-08

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-505086-83-00

ClinicalTrials.gov

NCT06315751

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Safety

Change in tic severity score YGTSS-R

Secondary objectives 9

1. Impact on patient functioning
2. Change in severity of illness
3. Change in illness
4. Change in PUTS
5. Change in ADHD assessment
6. Impact on QoL, including ADL and functioning
7. Effect on metabolic safety
8. Evaluation of safety and tolerability of gemlapodect including suicidality
9. PK

Conditions and MedDRA coding

Tourette Syndrome

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Patients aged 18 years onwards, at the time of signing the ICF/informed assent form. Patients from 12 years to 17 years of age can be enrolled after regional regulatory approval for adolescent inclusion has been granted.
2. Moderate to severe TS as defined by DSM-5 diagnostic criteria and TS-CGI-S ≥ 4
3. Patient is treatment naive or previously treated patients in need of treatment alternative as per investigators judgemen
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. Contraception should be used as described in Appendix 3 (Section 10.3) of the Protocol .A female patient prior to reaching childbearing potential will be allowed into the study according to the judgement of the investigator and in agreement with the medical monitor with regular reassessment of their status, including accepting the requirement for monthly pregnancy testing, including approximately 28 days following the cessation of study medication.
7. Capable of giving signed informed consent or consent from their legal representative is obtained as described in Appendix 1 ((Section 10.1.3) of the Protocol which includes compliance with the requirements and restrictions listed in the ICF/informed assent form and in the protocol
8. Fluency in the language of the investigator, study staff, and the ICF/informed assent form when applicable

Exclusion criteria 17

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 (defined as ≥2 emergency room visits or ≥1 hospitalization for TS symptoms or its associated behavioral comorbidities), neuroacanthocytosis, autism, and history of known intellectual disability that would affect patient’s ability to comply with study procedures).
2. Patients with a known hypersensitivity to gemlapodect or any of the excipients of the product
3. Positive urine drug screen for cannabis, cocaine, or nonprescribed opiates
4. The person is an employee or family member of an employee of the Sponsor, Investigator, or study site personnel.
5. 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
6. Previous randomization in the present study
7. Current active diagnosis of severe anxiety, bipolar disorder, schizophrenia, major depressive disorder (MDD), or Parkinson’s disease. Patients with a history of comorbid psychiatric conditions, including obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD) and MDD, may participate in the study as long as their treatments have been stable for ≥ 1 month
8. A history of severe traumatic brain injury or stroke
9. 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. In particular, patients with moderate or severe hepatic impairment [Child Pugh class B (7-9 total points) or Child Pugh class C (10-15 total points)] and/or severe renal impairment (eGFR≤30 mL/min/1.73m2 ) are not eligible.
10. 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 enroll in the study.
11. Known DSM-5 diagnosis of substance abuse or dependence
12. Active suicidal ideation or behavior, as assessed by the answer “YES” to Items 4, or 5 on the C-SSRS Suicidal Ideation. Management of patients exhibiting such symptoms is described in Section 7.1.4.
13. Neurostimulation/deep brain stimulation for TS
14. Participation in another clinical study with a study intervention administered in the last 30 days
15. 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. Study participants prescribed cannabinoids for seizure disorders are not eligible for study participation. Recreational cannabinoids, regardless of their form of intake, which include tetrahydrocannabinol and/or cannabidiol, are prohibited.
16. Strong inhibitors and inducers of CYP3A4 as well as strong inhibitors and inducers of CYP2C8 are prohibited during the study and will be discontinued during the screening period; See Section 6.10.2.
17. The person is currently committed to an institution by virtue of an order issued either by the judicial or the administrative authorities

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in YGTSS-R total tic scores from baseline (randomization) to D85 for gemlapodect as compared to placebo

Secondary endpoints 15

1. Change in SDS from baseline (randomization) to D85 for gemlapodect as compared to placebo
2. Change in TS-CGI-S scale from baseline (randomization) to D85 for gemlapodect as compared to placebo
3. TS-CGI-C scale at D85 for gemlapodect as compared to placebo
4. PGI-C scale at D85 for gemlapodect as compared to placebo
5. Change in PUTS from baseline (randomization) to D85 for gemlapodect as compared to placebo
6. Change in ADHD-RS from baseline (randomization) to D85 for gemlapodect as compared to placebo
7. Change in C&A-GTS-QOL subscale from baseline (randomization) to D85 for gemlapodect as compared to placebo
8. Change in body weight and effect on blood glucose and lipids
9. Incidence and severity of AEs, including SAEs and AESI
10. Laboratory assessments
11. ECG assessment
12. Assessment of vital signs
13. Suicidality assessed by C-SSRS
14. Plasma concentrations of gemlapodect
15. Assessment of bodyweight changes over time from baseline

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Noema Pharma AG

Sponsor organisation

Noema Pharma AG

Address

Barfusserplatz 3

City

Basel Town

Postcode

4051

Country

Switzerland

Scientific contact point

Organisation

Noema Pharma AG

Contact name

Global Regulatory Affairs

Public contact point

Organisation

Noema Pharma AG

Contact name

Global Regulatory Affairs

Third parties 3

Locations

6 EU/EEA countries · 28 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 224 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

22 submissions — initial application plus substantial / non-substantial modifications