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

• ClinicalTrials.gov Identifier: NCT03649477
• Recruitment Status: Completed
• First Posted: August 28, 2018
• Results First Posted: November 17, 2021
• Last Update Posted: July 26, 2022
• Sponsor: Levo Therapeutics, Inc.
• Information provided by (Responsible Party): Levo Therapeutics, Inc.

Tracking Information

• First Submitted Date: August 24, 2018
• First Posted Date: August 28, 2018
• Results First Submitted Date: August 30, 2021
• Results First Posted Date: November 17, 2021
• Last Update Posted Date: July 26, 2022
• Actual Study Start Date: November 20, 2018
• Actual Primary Completion Date: May 13, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 30, 2021)

• Hyperphagia Behavior [ Time Frame: Baseline to Week 8 ]
  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.
• Obsessive and Compulsive Behaviors [ Time Frame: baseline to Week 8 ]
  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.

Original Primary Outcome Measures (submitted: August 24, 2018)

• Hyperphagia behavior [ Time Frame: baseline to Week 8 ]
  Change in hyperphagia (extreme hunger) as measured by the Hyperphagia Questionnaire for Clinical Trials (HQ-CT) Total Score versus placebo
• Obsessive and compulsive behaviors [ Time Frame: baseline to Week 8 ]
  Change in obsessive and compulsive behaviors as measured by the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) Total Score versus placebo

Current Secondary Outcome Measures (submitted: August 30, 2021)

• Anxiety [ Time Frame: Baseline to Week 8 ]
  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.
• Global Impression [ Time Frame: Week 8 ]
  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.
• Hyperphagia Behavior (Subset) [ Time Frame: Baseline to Week 8 ]
  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.

Original Secondary Outcome Measures (submitted: August 24, 2018)

• Anxiety [ Time Frame: baseline to Week 8 ]
  Change in participant anxiety as measured by the PWS Anxiety and Distress Questionnaire (PADQ) Total Score versus placebo
• Global impression [ Time Frame: baseline to Week 8 ]
  Change in Clinical Global Impression of Change (CGI-C) score versus placebo
• Hyperphagia behavior [ Time Frame: baseline to Week 8 ]
  Change in hyperphagia as measured by the change in specified subsets of HQ-CT questions versus placebo

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase 3 Study of Intranasal Carbetocin (LV-101) in Patients With Prader-Willi Syndrome
• Official Title: 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)
• Brief Summary: 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.

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
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Three parallel groups (two different doses of carbetocin and placebo) for the first 8 weeks; two parallel groups (two different doses of carbetocin) during 56 weeks of follow-up and the optional extension period

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

• Condition: Prader-Willi Syndrome

Intervention

• Drug: 3.2 mg intranasal carbetocin
  three times per day with meals
  Other Name: LV-101
• Drug: 9.6 mg intranasal carbetocin
  three times per day with meals
  Other Name: LV-101
• Drug: placebo
  three times per day with meals

Study Arms

• 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
  Intervention: Drug: placebo
• 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
  Intervention: Drug: 3.2 mg intranasal carbetocin
• 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
  Intervention: Drug: 9.6 mg intranasal carbetocin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 15, 2020): 130
• Original Estimated Enrollment (submitted: August 24, 2018): 175
• Actual Study Completion Date: July 9, 2022
• Actual Primary Completion Date: May 13, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 7 Years to 18 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, United States

Administrative Information

• NCT Number: NCT03649477
• Other Study ID Numbers: LV-101-3-01
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Levo Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Levo Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Levo Therapeutics, Inc.
• Verification Date: August 2021