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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | 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 |
|
| 3.2 mg of LV-101 | Experimental | 3.2 mg of LV-101 during first 8-weeks; remain on same dose during 56-week follow-up and optional extension periods |
|
| 9.6 mg of LV-101 | Experimental | 9.6 mg of LV-101 during first 8-weeks; remain on same dose during 56-week follow-up and optional extension periods |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 3.2 mg intranasal carbetocin | Drug | three times per day with meals |
|
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham | Birmingham | Alabama | 35233 | United States | ||
| Phoenix Children's Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36633570 | Derived | Roof E, Deal CL, McCandless SE, Cowan RL, Miller JL, Hamilton JK, Roeder ER, McCormack SE, Roshan Lal TR, Abdul-Latif HD, Haqq AM, Obrynba KS, Torchen LC, Vidmar AP, Viskochil DH, Chanoine JP, Lam CKL, Pierce MJ, Williams LL, Bird LM, Butler MG, Jensen DE, Myers SE, Oatman OJ, Baskaran C, Chalmers LJ, Fu C, Alos N, McLean SD, Shah A, Whitman BY, Blumenstein BA, Leonard SF, Ernest JP, Cormier JW, Cotter SP, Ryman DC. Intranasal Carbetocin Reduces Hyperphagia, Anxiousness, and Distress in Prader-Willi Syndrome: CARE-PWS Phase 3 Trial. J Clin Endocrinol Metab. 2023 Jun 16;108(7):1696-1708. doi: 10.1210/clinem/dgad015. |
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Subjects were randomized 1:1:1 at Baseline to receive the 9.6 mg/dose, 3.2 mg/dose, or placebo during the 8-week placebo-controlled period. A total of 130 subjects were evaluated (44 subjects in the 9.6 mg/dose arm, and 43 subjects each in the 3.2 mg/dose and placebo arms). Of these 130 subjects, 128 subjects (98.5%) completed the Week 8 visit and entered into the long-term follow-up period.
Participants were enrolled in three countries, the United States, Canada and Australia. The first participant was screened in November 2018, the first participant was enrolled in December 2018, and the last participant was enrolled in March 2020.
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| ID | Title | Description |
|---|---|---|
| FG000 | 9.6 mg of LV-101 | 9.6 mg of LV-101 during the 8-week placebo-controlled period 9.6 mg intranasal carbetocin: three times per day with meals |
| FG001 | 3.2 mg of LV-101 | 3.2 mg of LV-101 during the 8-week placebo controlled period 3.2 mg intranasal carbetocin: three times per day with meals |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 19, 2019 | Aug 30, 2021 |
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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
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| 9.6 mg intranasal carbetocin | Drug | three times per day with meals |
|
|
| placebo | Drug | three times per day with meals |
|
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 |
| Phoenix |
| Arizona |
| 85006 |
| United States |
| Children's Hospital of Los Angeles (USC) | Los Angeles | California | 90027 | United States |
| Rady Children's Hospital San Diego | San Diego | California | 92123 | United States |
| Children's Hospital Colorado | Aurora | Colorado | 80045 | United States |
| Children's National | Washington D.C. | District of Columbia | 20010 | United States |
| University of Florida | Gainesville | Florida | 32608 | United States |
| Ann & Robert H. Lurie Children's Hospital of Chicago | Chicago | Illinois | 60611 | United States |
| Kansas University Medical Center | Kansas City | Kansas | 66160 | United States |
| University of Harvard Boston Children's Hospital | Boston | Massachusetts | 02115 | United States |
| Children's Hospitals and Clinics of Minnesota | Saint Paul | Minnesota | 55102 | United States |
| Cardinal Glennon Children's Medical Center | St Louis | Missouri | 63104 | United States |
| Nationwide Children's Hospital | Columbus | Ohio | 43205 | United States |
| University of Oklahoma Health Sciences Center | Tulsa | Oklahoma | 74135 | United States |
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19107 | United States |
| Vanderbilt University School of Medicine | Nashville | Tennessee | 37212 | United States |
| Texas Children's Hospital | Houston | Texas | 77030 | United States |
| Children's Hospital of San Antonio | San Antonio | Texas | 78207 | United States |
| University of Utah | Salt Lake City | Utah | 84108 | United States |
| Queensland Children's Hospital | South Brisbane | Queensland | 4101 | Australia |
| University of Alberta | Edmonton | Alberta | T6G 2E1 | Canada |
| British Columbia Children's Hospital | Vancouver | British Columbia | V6H 3V4 | Canada |
| Toronto Hospital for Sick Kids | Toronto | Ontario | M5G 1X8 | Canada |
| CHU Ste Justine | Montreal | Quebec | H3T 1C5 | Canada |
| FG002 | Placebo | Matched intranasal placebo during the 8-week placebo controlled period placebo: three times per day with meals |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | 9.6 mg of LV-101 | 9.6 mg of LV-101 during the 8-week placebo-controlled period 9.6 mg intranasal carbetocin: three times per day with meals |
| BG001 | 3.2 mg of LV-101 | 3.2 mg of LV-101 during the 8-week placebo controlled period 3.2 mg intranasal carbetocin: three times per day with meals |
| BG002 | Placebo | Matched intranasal placebo during the 8-week placebo controlled period placebo: three times per day with meals |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Inclusion criteria was 7 to 18 years of age at Screening. Subjects who were 19 years of age at Baseline were still eligible to participate if all other eligibility criteria were met. | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Primary Analysis Set: A subset of the Full Analysis Set that included all subjects with at least one post-Baseline visit (i.e., Week 2 or Week 8) completed prior to March 01, 2020 and excluded all efficacy data collected on or after March 01, 2020. | Posted | Least Squares Mean | 95% Confidence Interval | score on a scale | Baseline to Week 8 |
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| Primary | 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. | Primary Analysis Set: A subset of the Full Analysis Set that included all subjects with at least one post-Baseline visit (i.e., Week 2 or Week 8) completed prior to March 01, 2020 and excluded all efficacy data collected on or after March 01, 2020. | Posted | Least Squares Mean | 95% Confidence Interval | score on a scale | baseline to Week 8 |
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| Secondary | 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. | Primary Analysis Set: A subset of the Full Analysis Set that included all subjects with at least one post-Baseline visit (i.e., Week 2 or Week 8) completed prior to March 01, 2020 and excluded all efficacy data collected on or after March 01, 2020. | Posted | Least Squares Mean | 95% Confidence Interval | score on a scale | Baseline to Week 8 |
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| Secondary | 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. | Primary Analysis Set: A subset of the Full Analysis Set that included all subjects with at least one post-Baseline visit (i.e., Week 2 or Week 8) completed prior to March 01, 2020 and excluded all efficacy data collected on or after March 01, 2020. | Posted | Least Squares Mean | 95% Confidence Interval | score on a scale | Week 8 |
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| Secondary | 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. | Primary Analysis Set: A subset of the Full Analysis Set that included all subjects with at least one post-Baseline visit (i.e., Week 2 or Week 8) completed prior to March 01, 2020 and excluded all efficacy data collected on or after March 01, 2020. | Posted | Least Squares Mean | 95% Confidence Interval | score on a scale | Baseline to Week 8 |
|
8-week placebo-controlled period
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 9.6 mg of LV-101 | 9.6 mg of LV-101 during the 8-week placebo controlled period 9.6 mg intranasal carbetocin: three times per day with meals | 0 | 44 | 0 | 44 | 20 | 44 |
| EG001 | 3.2 mg of LV-101 | 3.2 mg of LV-101 during the 8-weeks placebo-controlled period 3.2 mg intranasal carbetocin: three times per day with meals | 0 | 43 | 0 | 43 | 19 | 43 |
| EG002 | Placebo | Matched intranasal placebo during 8-week placebo-controlled period placebo: three times per day with meals | 0 | 43 | 0 | 43 | 10 | 43 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 23.0 | Systematic Assessment |
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| Upper respiratory tract infection | General disorders | MedDRA 23.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Nasal discomfort | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Flushing | Vascular disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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The COVID-19 pandemic began affecting this study in early March 2020 by substantially impacting the ability to safely enroll clinical study subjects, by requiring remote visits and monitoring, and by dramatically changing daily routines and social environments in this sensitive PWS population. Levo held new screening and enrollment in March 2020, and subsequently closed screening and enrollment in May 2020, resulting in the enrollment of 130 subjects instead of the 175 subjects planned.
This study is a multi-center study. Sponsor retains first publication rights for a period of time after conclusion of study. Study has not yet completed.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Vice President of Clinical Development | Levo Therapeutics | 1-847-901-9260 | contactus@levotx.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 8, 2020 | Aug 30, 2021 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D011218 | Prader-Willi Syndrome |
| ID | Term |
|---|---|
| D008607 | Intellectual Disability |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D000015 | Abnormalities, Multiple |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D025063 | Chromosome Disorders |
| D030342 | Genetic Diseases, Inborn |
| D000096803 | Imprinting Disorders |
| D009765 | Obesity |
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
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| Between 18 and 65 years |
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| >=65 years |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| 0.0162 |
0.05 threshold for statistical significance |
| Mean Difference (Net) |
| -3.136 |
| 2-Sided |
| 95 |
| -5.685 |
| -0.586 |
| Superiority |
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