| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| E.1.1.1 | Medical condition in easily understood language |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10018269 |
| E.1.2 | Term | Gilles de la Tourette syndrome |
| E.1.2 | System Organ Class | 100000004850 |
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| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To investigate the efficacy of sepranolone to reduce tic severity in patients with Tourette syndrome at 12 weeks |
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| E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of sepranolone to reduce tic related impairment in patients with Tourette syndrome at 12 weeks.
• To evaluate the efficacy of sepranolone to reduce the urge to tic in patients with Tourette syndrome at 12 weeks
• To evaluate the effect of sepranolone on activities of daily living in patients with Tourette syndrome at 12 weeks
• To evaluate the effect on Global clinical impression by sepranolone in patients with Tourette syndrome at 12 weeks.
Safety:
• To evaluate the safety and tolerability of Sepranolone in adolescent and adult patients with Tourette syndrome.
Explorative:
• To explore the exposure to sepranolone
• Explore the effect of sepranolone on symptoms of Obsessive-Compulsive Disorder (OCD) at week 12 |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Pediatric subjects:
1) provide written informed consent prior to any study related procedures
2) be diagnosed with Tourette syndrome according to the European diagnostic criteria that have been established by the European ESSTS Guidelines Group and based on the tenth International Classification of Disease (ICD-10) (Cath et al 2011).
3) be either male or female
4) be aged ≥12 and ≤17 years at the time of screening
5) have a BMI of for adolescents normal for age ± 2SD (See appendix D)
6) Have a tic severity at screening graded as moderate to severe, corresponding to a tic score of ≥20 on the Yale Global Tic Severity Scale Total Score (Leckman et al, 1998).
7) The patient may have a comorbidity of Obsessive-Compulsive Disease (OCD) that, in the opinion of the Investigator, does not interfere with the evaluation of symptoms of the patient’s Tourette syndrome.
8) No treatment or ongoing stable treatment of cognitive therapy and/or stable doses of any allowed chronic or PRN concomitant treatment during three months prior to entering of baseline phase, at the discretion of the investigator. Hormonal treatments are not allowed. See also Disallowed and restricted medications list (Appendix J).
9) For a female subject of childbearing potential, agree to use sufficient contraception.
10) For a male patient, he must:
a. agree to use sufficient barrier contraception or be truly abstinent. He must also agree to continue sufficient contraception for three months after completing study treatment.
11) for women of childbearing potential: a negative pregnancy test at Visit 1 and 3.
for both child and parent/custodian, able to understand and communicate with the study doctor and staff.
13) able to accept the use of injectable medication, adhere to the medication regimens and perform study procedures.
14) for the child and parent/custodian, able to read and comprehend written instructions and be willing to complete all procedures and assessments required by this protocol.
Adult Subjects:
1) have given his/her written informed consent.
2) be diagnosed with Tourette syndrome according to the European diagnostic criteria that have been established by the European ESSTS Guidelines Group and based on the tenth International Classification of Disease (ICD-10) (Cath et al 2011).
3) be either male or female.
4) be between ≥18 and ≤55 years at time the screening visit.
5) have a BMI ≥18.5 kg/m2 or ≤32 kg/m2.
6) Have a tic severity at screening graded as moderate to severe, corresponding to a tic score of ≥20 on the Yale Global Tic Severity Scale Total Score (Leckman et al, 1998).
7) The patient may have a comorbidity of Obsessive-Compulsive Disease (OCD) that, in the opinion of the Investigator, does not interfere with the evaluation of symptoms of the patient’s Tourette syndrome.
8) No treatment or ongoing stable treatment of cognitive therapy and/or stable doses of any allowed chronic or PRN concomitant treatment during three months prior to entering of baseline phase, at the discretion of the investigator. Hormonal treatments are not allowed. See also Disallowed and restricted medications list (Appendix J).
9) For a female subject of childbearing potential, agree to use sufficient contraception.
10) For a male patient, he must:
a. agree to use sufficient barrier contraception or be truly abstinent. He must also agree to continue sufficient contraception for three months after completing study treatment.
11) for women of childbearing potential: a negative pregnancy test at Visit 1 and 3.
be able to understand and communicate with the study doctor and staff.
13) able to use of injectable medication, adhere to the medication regimens and perform study procedures.
14) be able to read and comprehend written instructions and be willing to complete all procedures and assessments required by this protocol.
Please see protocol section 4.3 for full set of inclusion criterias. |
|
| E.4 | Principal exclusion criteria |
Pediatric subjects:
1) has participated in a clinical study and received active drug in such a study within 30 days or 5 study drug half-lives, whichever the longest, prior to the first study visit.
2) has, in the investigator's opinion, evidence and/or history of any clinically significant neurological disease, or other conditions potentially interfering with study assessments.
3) has or has had a malignant disease.
4) has a history of other unstable or clinically significant medical condition that in the opinion of the investigator that would pose a risk to the subject safety or interfere with study evaluation, including e.g. unstable cardiovascular disease, uncontrolled diabetes, unstable thyroid disease, renal impairment or hepatic impairment (Gilbert syndrome allowed).
5) has HIV or ongoing hepatitis.
6) has any clinically significant findings in vital signs, laboratory results, or ECG that in the opinion of the investigator would pose a risk to the subject safety or interfere with study evaluation.
7) has allergies to ingoing study drug components or a history of true anaphylactic reactions.
8) have had a blood loss ≥250 mL within 56 days prior to screening.
9) is pregnant or breast-feeding, or planning pregnancy during the study period.
10) has an unstable major psychiatric disorder according to DSM 5® criteria.
11) has a history of drug abuse or dependency that in the judgement of the investigator may interfere with study compliance.
12) is taking hormonal contraceptives (hormonal IUD is allowed). For injectable hormonal contraceptives, a 6-month washout is required.
taking disallowed medications or allowed with restrictions with respect to their use prior to or during the full study period (this list is not comprehensive).
13) taking disallowed medications or allowed with restrictions with respect to their use prior to or during the full study period (this list is not comprehensive).
14) the subject or parent/custodian is a member of investigational site staff or relative of the investigator.
Adult subjects:
1) has participated in a clinical study and received active drug in such a study within 30 days or 5 study drug half-lives, whichever the longest, prior to the first study visit.
2) has, in the investigator's opinion, evidence and/or history of any clinically significant neurological disease, or other conditions potentially interfering with study assessments.
3) has or have had a malignant disease within the previous 5 years (except non-melanoma skin cancer, cervical or breast ductal carcinoma in situ).
4) has a history of other unstable or clinically significant medical condition that in the opinion of the investigator would pose a risk to the subject safety or interfere with study evaluation, including e.g. unstable cardiovascular disease, uncontrolled diabetes, unstable thyroid disease, renal impairment or hepatic impairment (Gilbert syndrome allowed).
5) has HIV or ongoing hepatitis.
6) has any clinically significant findings in vital signs, laboratory results, or ECG that in the opinion of the investigator would pose a risk to the subject safety or interfere with study evaluation.
7) has allergies to ingoing study drug components or a history of true anaphylactic reactions.
8) have a blood loss ≥550 mL or donated blood within 30 days prior to screening.
9) is pregnant or breast-feeding, or planning pregnancy during the study period.
10) has an unstable major psychiatric disorder according to DSM 5® criteria.
11) has a history of drug abuse or dependency that in the judgement of the investigator may interfere with study compliance.
12) is taking hormonal contraceptives (hormonal IUD is allowed). For injectable hormonal contraceptives, a 6-month washout is required.
13) taking disallowed medications or allowed with restrictions with respect to their use prior to or during the full study period (this list is not comprehensive).
14) is a member of investigational site staff or relative of the investigator.
Please see protocol section 4.3 for full set of exclusion criterias. |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| Change from baseline YGTSS total score |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Total Score at week 4, 8 and 12. |
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| E.5.2 | Secondary end point(s) |
• Change from baseline YGTSS Impairment Score at week 4, 8 and 12.
• Change from baseline PUTS score at week 4, 8 and 12.
• Change in the Gilles de la Tourette Syndrome - Quality of Life (GTS-QOL) physical/activities of daily living (ADL) subscale at week 4, 8 and 12.
• Change from baseline in the Tourette Syndrome-Clinical Global Impression (TS-CGI) score at week 4, 8 12.
• Plasma levels of isoallopregnanolone at week 0, 4, 8 and 12.
Explorative endpoints: • Plasma and/ or saliva concentrations of isoallopregnanolone and allopregnanolone
• Change from baseline in the Yale–Brown Obsessive–Compulsive Scale(Y-BOCS) / Children’s Yale–Brown Obsessive–Compulsive Scale (CY-BOCS) at week 4, 8 and 12
Safety endpoints: 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
• Injection related events
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
YGTSS, PUTS, GTS-QOL, TS-CGI, Y-BOCS/CY-BOCS at week 4, 8 and 12.
Plasma levels of isoallopregnanolone at week 0, 4, 8 and 12.
Safety from subject has signed informed consent form and during participation in study until last follow-up visit. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| Standard of Care (control group) |
|
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 5 |
| E.8.9.1 | In the Member State concerned days | |
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