Study of Tesomet With Open-label Extension in Subjects With Prader-Willi Syndrome (PWS)

A Phase 2b, Double-blind, Randomized, Placebo-controlled, Multi-center, 16-week Dose Finding, Safety and Efficacy Study With Open-label Extension (OLE) Period of Tesomet in Subjects With Prader-Willi Syndrome

This study will evaluate the safety and efficacy of Tesomet (tesofensine + metoprolol) in subjects with PWS.

Study Overview

• Status: Withdrawn
• Conditions: Prader-Willi Syndrome
• Intervention / Treatment: Other: Placebo; Drug: Tesomet

Detailed Description

For the double-blind portion of the study, dosing will be initiated in a subgroup of adults who are 18-65 years of age. Following independent Data Monitoring Board review of subgroup safety data, and review and confirmation to proceed by FDA, enrollment of subjects <18 years of age will commence.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Lansing, Michigan, United States, 48912
      • Sparrow Clinical Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 years to 61 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Subject and their legally authorized representative must be willing to provide informed consent
• Confirmed genetic diagnosis of PWS

• Body mass index (BMI) within the following range at Screening:

  1. Female and male subjects 18 to 65 years of age: 27 to 60 kg/m2; or
  2. Female and male subjects 13 to 17 years of age with BMI that is at least 85th percentile for age and sex;
• Female subjects must be of non-child-bearing potential
• Documented stable body weight
• Moderate hyperphagia at Screening and at Baseline
• Participants must have a reliable and stable caregiver who should be able to spend an adequate amount of time with the participants to be able to address behaviors, activities and symptoms
• Male subjects who are sexually active must be surgically sterile

Key Exclusion Criteria:

• Females who are pregnant, breastfeeding, or actively intending to become pregnant during the study

• Sitting BP that meets the following criteria after 5 minutes of rest at Screening:

  1. Adult subjects with systolic BP >/=145 mmHg or <100 mmHg; or
  2. Adult subjects with diastolic BP >/=95 mmHg or <70 mmHg; or
  3. Adolescent subjects with a systolic or diastolic BP that is 95th percentile or greater for age and sex
• Type 1 diabetes mellitus
• History of dementia (eg, Alzheimer's disease, Parkinson's disease)
• History of bulimia or anorexia nervosa
• History of major depressive disorder within 2 years prior to Screening, or any history of other severe psychiatric disorder (eg, schizophrenia, bipolar disorder), or symptoms of delusions, hallucinations, or mania/hypomania within 90 days prior to Screening, as described by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5)
• Uncontrolled endocrine disorders (eg, Cushing syndrome, Addison's, hypothyroidism, hyperthyroidism)
• Medical condition or recent systemic infection that, in the opinion of the Investigator, could impact the safety of the subject
• Use of prohibited medications, including current use of SSRIs/SNRIs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Once-daily PO for 16 weeks during the double-blind period; then if eligible for OLE, once-daily dosing for 36 weeks of the highest tolerated Tesomet dose from the double-blind period	Other: Placebo; Inactive comparator; Drug: Tesomet; Fixed-dose combination; Other Names: tesofensine; metoprolol
Experimental: Tesomet Low Dose; Once-daily PO for 16 weeks during the double-blind period; then if eligible for OLE, once-daily dosing for 36 weeks of the highest tolerated dose from the double-blind period	Drug: Tesomet; Fixed-dose combination; Other Names: tesofensine; metoprolol
Experimental: Tesomet Medium Dose; Once-daily PO for 16 weeks during the double-blind period; then if eligible for OLE, once-daily dosing for 36 weeks of the highest tolerated dose from the double-blind period	Drug: Tesomet; Fixed-dose combination; Other Names: tesofensine; metoprolol
Experimental: Tesomet High Dose; Once-daily PO for 16 weeks during the double-blind period; then if eligible for OLE, once-daily dosing for 36 weeks of the highest tolerated dose from the double-blind period	Drug: Tesomet; Fixed-dose combination; Other Names: tesofensine; metoprolol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hyperphagia	Change in Hyperphagia Questionnaire for Clinical Trials (HQ-CT) total score	Baseline to Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Body Weight	Percentage change in body weight	Baseline to Week 16
Hyperphagia Severity (Caregiver)	Change in caregiver rating of hyperphagia severity	Baseline to Week 16
Hyperphagia Change (Caregiver)	Proportion of caregiver responses for change in subject's hyperphagia	Week 16
PWS Severity (Clinician)	Change in clinician rating of the subject's PWS severity	Baseline to Week 16
Overall Status Change (Clinician)	Proportion of clinician responses for change in subject's overall clinical status	Week 16

Collaborators and Investigators

• Sponsor: Saniona
• Investigators: Study Director: Sophie Guillaume, MS, Saniona

Study record dates

Study Major Dates

• Study Start (Actual): December 28, 2021
• Primary Completion (Actual): December 9, 2022
• Study Completion (Actual): December 9, 2022

Study Registration Dates

• First Submitted: January 5, 2022
• First Submitted That Met QC Criteria: January 5, 2022
• First Posted (Actual): January 20, 2022

Study Record Updates

• Last Update Posted (Estimate): December 13, 2022
• Last Update Submitted That Met QC Criteria: December 9, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: hyperphagia
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Congenital Abnormalities; Overnutrition; Nutrition Disorders; Genetic Diseases, Inborn; Intellectual Disability; Abnormalities, Multiple; Chromosome Disorders; Obesity; Syndrome; Prader-Willi Syndrome; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Autonomic Agents; Peripheral Nervous System Agents; Sympatholytics; Adrenergic beta-1 Receptor Antagonists; Metoprolol
• Other Study ID Numbers: TM006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: The Sponsor will consider requests from qualified researchers for access to TM006 study materials
• IPD Sharing Time Frame: Following completion of Tesomet clinical development
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No