Phase 3 Study of Intranasal Carbetocin (LV-101) in Patients With Prader-Willi Syndrome (CARE-PWS)

Phase 3, Randomized, Double-Blind, Placebo-Controlled, 8-week Clinical Study to Assess the Efficacy, Safety, and Tolerability, of Intranasal Carbetocin (LV-101) in Prader-Willi Syndrome (PWS) With Long Term Follow-Up (CARE-PWS)

This Phase 3 study is designed to test the effectiveness of intranasal carbetocin (LV-101) in participants with Prader-Willi syndrome (PWS). Carbetocin is an oxytocin analog (a man-made chemical that is like oxytocin). This study will also evaluate the safety and tolerability of LV-101.

Study Overview

• Status: Completed
• Conditions: Prader-Willi Syndrome
• Intervention / Treatment: Drug: placebo; Drug: 3.2 mg intranasal carbetocin; Drug: 9.6 mg intranasal carbetocin

Detailed Description

This is a Phase 3 randomized, double-blind study with an 8-week, placebo-controlled period designed to test the effectiveness, safety, and tolerability of LV-101 in participants with PWS.

Effectiveness will be measured using both caregiver-reported and clinician-reported measures of hyperphagia (extreme hunger), obsessive and compulsive behaviors, and anxiety. Safety and tolerability will be measured by adverse events, laboratory tests, and physical exams.

After the 8-week placebo-controlled period, there will be a long-term follow-up period of 56 weeks and an optional extension period after study week 64 during which all participants will receive active treatment with LV-101. At Week 8, participants who were randomized to placebo in the placebo-controlled period will be randomized to one of the two LV-101 doses, administered three times per day before meals.

• Study Type: Interventional
• Enrollment (Actual): 130
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Queensland Children's Hospital
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2E1
      • University of Alberta
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 3V4
      • British Columbia Children's Hospital
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • Toronto Hospital for Sick Kids
  • Quebec
    • Montréal, Quebec, Canada, H3T 1C5
      • CHU Ste Justine
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Phoenix Children's Hospital
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital of Los Angeles (USC)
    • San Diego, California, United States, 92123
      • Rady Children's Hospital San Diego
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National
  • Florida
    • Gainesville, Florida, United States, 32608
      • University of Florida
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Kansas University Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • University of Harvard Boston Children's Hospital
  • Minnesota
    • Saint Paul, Minnesota, United States, 55102
      • Children's Hospitals and Clinics of Minnesota
  • Missouri
    • Saint Louis, Missouri, United States, 63104
      • Cardinal Glennon Children's Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74135
      • University of Oklahoma Health Sciences Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Children's Hospital of Philadelphia
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University School of Medicine
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital
    • San Antonio, Texas, United States, 78207
      • Children's Hospital of San Antonio
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 14 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Genetically-confirmed Prader-Willi syndrome
• Provide voluntary, written informed consent (parent(s) / legal guardian(s) of participant); provide voluntary, written assent (participants, as appropriate)
• PWS Nutritional Phase 3 (hyperphagic, rarely feels full)

Exclusion Criteria:

• Living in a group home
• Genetically diagnosed Schaaf-Yang syndrome or other genetic, hormonal, or chromosomal cognitive impairment
• New food-related interventions, including environment or dietary restrictions, within 1 month of screening
• Dose of any allowed chronic concomitant medications or supplements that have not been stable for ≥3 months prior to the study or is not expected to remain stable while participating in the study; adjustments in growth hormone dose ≤10% are not exclusionary
• Presence of cardiovascular disorders, epilepsy, frequent migraines, or severe asthma
• More than 3 episodes of sinusitis in the 12 months prior to Screening Visit or presence of nasal diseases that may affect deposition of intranasal medication
• Unwilling to abstain from nasal saline, other nasal irrigation, or other intranasal medications for 2 weeks prior to the Baseline visit and during the 8-week, placebo-controlled period of the study
• Use of weight loss medication, oxytocin, carbetocin, or vasopressin in the 6 months prior to screening
• Participation in an interventional research study involving another investigational medication or device in the 6 months prior to screening or during the study
• Based on the judgment of the Investigator, is unsuitable for the study for any reason, including but not limited to unstable medical condition, inability to comply with the protocol, or other risk to subject or to the integrity of the study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; matched placebo during first 8-weeks; prospectively randomized 1:1 to either one of the two doses of carbetocin during 56-week follow-up and optional extension periods	Drug: placebo; three times per day with meals
Experimental: 3.2 mg of LV-101; 3.2 mg of LV-101 during first 8-weeks; remain on same dose during 56-week follow-up and optional extension periods	Drug: 3.2 mg intranasal carbetocin; three times per day with meals; Other Names: LV-101
Experimental: 9.6 mg of LV-101; 9.6 mg of LV-101 during first 8-weeks; remain on same dose during 56-week follow-up and optional extension periods	Drug: 9.6 mg intranasal carbetocin; three times per day with meals; Other Names: LV-101

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hyperphagia Behavior	Change in hyperphagia (extreme hunger) as measured by the Hyperphagia Questionnaire for Clinical Trials (HQ-CT) Total Score versus placebo. Score range: 0-36; higher scores mean a worse outcome. Reduction in score indicates improvement.	Baseline to Week 8
Obsessive and Compulsive Behaviors	Change in obsessive and compulsive behaviors as measured by the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) Total Score versus placebo. Score range: 0-40; higher scores mean a worse outcome. Reduction in score indicates improvement.	baseline to Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anxiety	Change in participant anxiety as measured by the PWS Anxiety and Distress Questionnaire (PADQ) Total Score versus placebo. Score range: 0-56; higher scores mean a worse outcome. Reduction in score indicates improvement.	Baseline to Week 8
Global Impression	Clinical Global Impression of Change (CGI-C) score versus placebo. Score range: 1-7; higher scores mean a worse outcome. Reduction in score indicates improvement.	Week 8
Hyperphagia Behavior (Subset)	Change in hyperphagia as measured by the change in specified subsets of HQ-CT questions versus placebo. Score range: 0-24; higher scores mean a worse outcome. Reduction in score indicates improvement.	Baseline to Week 8

Collaborators and Investigators

• Sponsor: Levo Therapeutics, Inc.

Publications and helpful links

Helpful Links

• Levo CARE-PWS Study

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2018
• Primary Completion (Actual): May 13, 2020
• Study Completion (Actual): July 9, 2022

Study Registration Dates

• First Submitted: August 24, 2018
• First Submitted That Met QC Criteria: August 24, 2018
• First Posted (Actual): August 28, 2018

Study Record Updates

• Last Update Posted (Actual): July 26, 2022
• Last Update Submitted That Met QC Criteria: July 18, 2022
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Prader-Willi syndrome; PWS; carbetocin
• 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; Reproductive Control Agents; Oxytocics; Oxytocin; Carbetocin
• Other Study ID Numbers: LV-101-3-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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