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

NCT03649477 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: LV-101-3-01
• Study Type: interventional
• Target: 130
• Locations: 3 countries
• Sites: 24

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.

Conditions

Prader-Willi Syndrome

Keywords

PWS; Prader-Willi syndrome; carbetocin

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• Anxiety

  Baseline to Week 8

• Global Impression

  Week 8

• Hyperphagia Behavior (Subset)

  Baseline to Week 8

Study Arms (3)

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

Drug: placebo

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

Drug: 3.2 mg intranasal carbetocin

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

Drug: 9.6 mg intranasal carbetocin

Interventions

3.2 mg intranasal carbetocin DRUG

three times per day with meals

Also known as: LV-101

3.2 mg of LV-101

9.6 mg intranasal carbetocin DRUG

three times per day with meals

Also known as: LV-101

9.6 mg of LV-101

placebo DRUG

three times per day with meals

Placebo

Eligibility Criteria

• Age: 7 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Levo Therapeutics, Inc.: lead

Study Sites (24)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Phoenix Children's Hospital

Phoenix, Arizona, 85006, United States

Location

Children's Hospital of Los Angeles (USC)

Los Angeles, California, 90027, United States

Location

Rady Children's Hospital San Diego

San Diego, California, 92123, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Children's National

Washington D.C., District of Columbia, 20010, United States

Location

University of Florida

Gainesville, Florida, 32608, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Kansas University Medical Center

Kansas City, Kansas, 66160, United States

Location

University of Harvard Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Children's Hospitals and Clinics of Minnesota

Saint Paul, Minnesota, 55102, United States

Location

Cardinal Glennon Children's Medical Center

St Louis, Missouri, 63104, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

University of Oklahoma Health Sciences Center

Tulsa, Oklahoma, 74135, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19107, United States

Location

Vanderbilt University School of Medicine

Nashville, Tennessee, 37212, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Children's Hospital of San Antonio

San Antonio, Texas, 78207, United States

Location

University of Utah

Salt Lake City, Utah, 84108, United States

Location

Queensland Children's Hospital

South Brisbane, Queensland, 4101, Australia

Location

University of Alberta

Edmonton, Alberta, T6G 2E1, Canada

Location

British Columbia Children's Hospital

Vancouver, British Columbia, V6H 3V4, Canada

Location

Toronto Hospital for Sick Kids

Toronto, Ontario, M5G 1X8, Canada

Location

CHU Ste Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Related Publications (1)

• 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.

  PMID: 36633570 DERIVED

MeSH Terms

Conditions

Prader-Willi Syndrome

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Imprinting Disorders; Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases

Limitations and Caveats

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.

Results Point of Contact

• Title: Vice President of Clinical Development
• Organization: Levo Therapeutics

contactus@levotx.com

1-847-901-9260

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: August 24, 2018
• First Posted: August 28, 2018
• Study Start: November 20, 2018
• Primary Completion: May 13, 2020
• Study Completion: July 9, 2022
• Last Updated: July 26, 2022
• Results First Posted: November 17, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (19); AU (1); CA (4)