Prader-Willi Syndrome MedDRA version: 20.0 Level: PT Classification code 10036476 Term: Prader-Willi syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Sponsors
Saniona A/S
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. The subject and their legally authorized representative (ie, parent, legal guardian) and the caregiver must be willing to sign and receive a copy of their respective informed consent form(s) (ICF) after the nature and risk of study participation have been fully explained; a. Informed consent(s) [and assent(s) for subjects below the legal age of consent when applicable] signed by the subject, parent, or legal guardian, as appropriate, prior to the initiation of any study procedures; and b. informed consent(s) from the caregiver, signed prior to the initiation of any study procedures; 2. Confirmed genetic diagnosis of PWS via the central laboratory (Note: past genetic documentation is acceptable for enrollment with confirmatory methylation test done in parallel); 3. Female and male subjects aged 13 to 65 years at the time of informed consent; 4. Female subjects of non-childbearing potential (WONCBP); defined as follows: surgically sterile (ie, had a hysterectomy, or bilateral oophorectomy, or bilateral salpingectomy =6 months prior to the first dose of study drug); or Postmenopausal (no menses) for at least 1 year prior to the first dose of study drug. Postmenopausal status must be confirmed by follicle-stimulating hormone (FSH) testing at screening; 5. Body mass index (BMI) within the following range at Screening: a. Female and male subjects 18 to 65 years of age: 27 to 60 kg/m2; or b. Female and male subjects 13 to 17 years of age with a BMI ?85th percentile for age and sex; 6. Documented stable body weight (gain/loss =13 at both Screening and at Baseline (prior to randomization) with no more than ± 3 points difference between scores; 8. A score of 4 (moderately ill) or higher on the Clinical Global Impression of PWS Severity scale (CGIS, Appendix A) as assessed by the Clinician at Screening and at Baseline; 9. Subjects must have a consistent and reliable caregiver, able and willing to be trained and comply with study requirements, and should spend at least 4 waking hours/day for a minimum of 5 days a week with this caregiver for at least 6 months prior to Screening with no planned changes in caregiver and/or duration of time spent with the caregiver throughout study participation; 10. Normal lipid profile as per central laboratory normal ranges at Screening or, if elevated, (ie, outside normal ranges, per the central laboratory), the subject is well managed on a stable dose of lipid-lowering medication(s) for >=90 days prior to Screening and during the study; 11. Growth hormone and sex hormones are allowed, but the subject must be on a stable dose of these medications ?90 days prior to Screening with no plans for dose modification during the course of the study; 12. Type 2 diabetes mellitus (T2DM) is allowed, provided that all of the following criteria are met: a. Hemoglobin A1c (HbA1c) = 90 days prior to Screening; 13. Females of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Baseline; 14. Females of childbearing potential and males must be willing to use a highly effective form of birth control from Screening until 90 days after their last dose of study drug; 15. Male subjects must agree not to donate sperm fro
Exclusion criteria
Exclusion criteria: 1. Use of any prohibited medication 2. Planned change of residency during the course of the study 3. Genotypic CYP2D6-poor metabolizers and CYP2D6 ultra-rapid metabolizers as confirmed by the central laboratory at Screening 4. Sitting BP that meets the following criteria after 5 minutes of rest at Screening: a. Adult subjects with systolic BP >= 145 mmHg or = 95 mmHg or =95th percentile for age and sex; 5. HR >= 95 bpm or 450 msec for males and >470 msec for females at Screening (by central read) 7. Hypersensitivity or contraindication to tesofensine or metoprolol 8. Type 1 diabetes mellitus 9. History of dementia 10. History of bulimia or anorexia nervosa 11. Subject has a rare hereditary problem of fructose intolerance, glucose galactose malabsorption, or sucrase-isomaltose insufficiency 12. History of clinically significant cardiac disorders as determined by the Investigator including, but not limited to, arrhythmia, myocardial infarction, prolonged QT syndrome, cardiomyopathy, New York Heart Association classification level II or greater heart failure, or decompensated heart failure as determined by the Investigator 13. Medical history of stroke or transient ischemic attack 14. Subjects who, in the Investigator’s judgment, are actively suicidal and therefore deemed to be at significant risk for suicide, or: a. Subjects who answer “yes” to Question 4 of the Columbia-Suicide Severity Rating Scale (C-SSRS); or b. Subjects who answer "yes" to Question 5 of the C-SSRS (Active Suicidal Ideation with Specific Plan and Intent) on the "Suicidal Ideation" portion of the C-SSRS or c. Subjects who answer "yes" to any of the suicide-related behaviors (actual attempt, interrupted attempt, aborted attempt, preparatory act or behavior) on the "Suicidal Behavior" portion of the C-SSRS; and the ideation or behavior occurred within 2 years prior to Screening; 15. Subjects who experience any of the following active clinical symptoms within 90 days prior to Screening, as defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) and clinical judgment supported by the Brief Psychiatric Rating Scale (BPRS) administered centrally: a. Delusions; b. Hallucinations; c. Major depressive disorder; d. Hypomania; or e. Suicidality; 16. Subjects who answer “yes” to the self-mutilation/self-injury question in the C-SSRS at Screening and/or Baseline 17. Participation in another interventional study within 90 days prior to Screening or any prior participation in a tesofensine or Tesomet clinical study 18. Uncontrolled endocrine disorders 19. Underlying liver impairment as evidenced by abnormal liver function test results at Screening, including alanine aminotransferase or aspartate aminotransferase abnormalities >3 x the upper limit of normal, or total bilirubin >1.5 x the upper limit of normal (except in cases of diagnosed Gilbert’s Syndrome) 20. Underlying kidney impairment, defined as estimated glomerular filtration rate <= 60 mL/min/1.73 m2 (using the Schwartz equation), as determined by Screening laboratory assessments performed by the central laboratory 21. Planned major surgery which, in the Investigator’s opinion, will interfere significantly with subject safety or compliance 22. Subjects with a history of substance abu
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objectives of the study are: • To examine the efficacy of Tesomet over 16 weeks on hyperphagia in adult and adolescent subjects with PWS and to inform the dose selections for the Phase 3 study; and • To assess the safety and tolerability of Tesomet over 16 weeks in adult and adolescent subjects with PWS. ;Secondary Objective: The secondary objectives of the study are: • To examine the efficacy of Tesomet on body weight in adult and adolescent subjects with PWS; • To examine the efficacy of Tesomet on hyperphagia based on Caregivers’ Global Impressions of Hyperphagia Severity and Change in adult and adolescent subjects with PWS; • To examine the efficacy of Tesomet on overall health based on Clinicians’ Global Impressions of PWS Severity and Change in adult and adolescent subjects with PWS; • To examine the effects of Tesomet on heart rate (HR) and blood pressure (BP) in adult and adolescent subjects with PWS; and • To examine the pharmacokinetic (PK) profile of tesofensine and metoprolol in adult and adolescent subjects with PWS.;Primary end point(s): Efficacy endpoint : The primary efficacy endpoint is the change in total HQ-CT score from Baseline to Week 16. Safety endpoints: • The incidence of treatment-emergent adverse events (TEAEs) of special interest (secondary endpoint); • The incidence of TEAEs and treatment-emergent serious adverse events (TESAEs); • The incidence of MACE; • Laboratory evaluation (chemistry and hematology) results at Baseline and at all site visits; • Vital sign measurements at Baseline and at Week 8 and Week 16; • ECG assessments at Baseline and at Week 8 and Week 16; •Physical examination findings at Baseline and at Week 8 and Week 16; • C-SSRS administered by a trained rater at Baseline and at all visits; and • The Aberrant Behavior Checklist (ABC) completed by the caregiver at Baseline and at all visits to assess the change in behavior.;Timepoint(s) of evaluation of this end point: from Baseline to Week 16 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • The change in body weight (%) from Baseline to Week 16; • The change in the Caregiver Global Impression of Hyperphagia Severity scale (CaGI-H-S) from Baseline to Week 16; • The proportion of responses to the Caregiver Global Impression of Hyperphagia Change scale (CaGI-H-C) at Week 16; • The change in the Clinical Global Impression of PWS Severity scale (CGIS) from Baseline to Week 16; and • The proportion of responses to the Clinician Global Impression of PWS Change scale (CGIC) at Week 16. ;Timepoint(s) of evaluation of this end point: Baseline to Week 16 | — |
Countries
Australia, Belgium, France, Ireland, Italy, New Zealand, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactClinical Trials Information
Medpace
Outcome results
None listed