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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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)

Conditions
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Prader-Willi Syndrome

Intervention / Treatment
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* Drug: 3.2 mg intranasal carbetocin
* Drug: 9.6 mg intranasal carbetocin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>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<br>* three times per day with meals<br>|
| Experimental: 3.2 mg of LV-101<br>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<br>* three times per day with meals<br>* Other names: LV-101;|
| Experimental: 9.6 mg of LV-101<br>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<br>* three times per day with meals<br>* Other names: LV-101;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PWS, Prader-Willi syndrome, carbetocin