Study to Evaluate Efficacy, Safety, and Tolerability of RGH-706 in Prader-Willi Syndrome

Prader-Willi Syndrome Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-controlled, Multi-center, 2-part, Phase 2 Study to Evaluate Efficacy, Safety, and Tolerability of RGH-706 in Prader-Willi Syndrome

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05322096
• Other study ID #: RGH-706-003
• Secondary ID: 2021-004262-35
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: September 22, 2022
• Est. completion date: April 2024

Study information

• Verified date: November 2023
• Source: Gedeon Richter Plc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RGH-706 is a novel, potent, and orally active MCHR1 antagonist drug candidate discovered and being developed by Gedeon Richter Plc. for weight management. This will be the first Phase 2, proof-of-concept study using RGH-706 and is the third study in the clinical development program for RGH-706. The aim of this study is to evaluate the efficacy, safety, and tolerability of RGH-706 in patients with Prader-Willi Syndrome (PWS).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 176
• Est. completion date: April 2024
• Est. primary completion date: April 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 17 Years and older

Eligibility

Age Limits:

• In United States (USA), minimum age will be 17 years old.
• In European Union (EU) countries, minimum age will be 18 years old.

Inclusion Criteria:

• Male or female patients aged =17 years in USA at screening or aged =18 years in EU at screening
• Genetically confirmed diagnosis of PWS
• HQ-CT total score =14 at screening
• Body weight =40 kg/88 lbs and =200 kg/450 lbs
• Stable body weight
• Negative pregnancy test for females of childbearing potential and nonlactating at screening.
• Patients must be able to provide or have a parent or guardian who is able to provide written informed consent and/or assent (as applicable)
• Patients must have at least 1 consistent and reliable primary caregiver

Exclusion Criteria:

• Severe psychiatric disorders (eg, schizophrenia, bipolar disorder, or major depressive disorder), recent (within 6 months)
• Risk of suicide according to the investigator's judgment
• Uncontrollable diabetes mellitus or diabetes mellitus requiring insulin administration
• Poorly controlled hypothyroidism or hyperthyroidism
• Chronic or acute liver disease
• History of bariatric surgery procedure
• Uncontrolled obstructive sleep apnea.
• History of malignancy within 5 years of screening
• Systolic blood pressure (BP) =160 mmHg and/or diastolic BP =100 mmHg, pulse rate =100/min at screening.
• Use of weight-lowering pharmacotherapy within 6 months prior to screening.
• Known QT prolongation
• Clinically relevant laboratory abnormalities
• Any other condition that, in the investigator's opinion, might indicate that the patient is unsuitable for the study

Related Conditions & MeSH terms

• Prader-Willi Syndrome
• Syndrome

Intervention

Drug:
• RGH-706
Capsules Oral administration
• Placebo
Capsules Oral administration

Locations

Country	Name	City	State
Czechia	Fakultní Nemocnice v Motole	Prague
Czechia	General University Hospital	Prague
France	Centre Hospitalier Universitaire d'Angers	Angers
France	Centre Hospitalier Régional Universitaire de Lille (CHRU) - Hôpital Claude Huriez	Lille
France	Centre Hospitalier Lyon-Sud	Pierre-Bénite
France	Hôpital Larrey	Toulouse
Italy	Azienda Ospedaliero-Universitaria Careggi	Firenze
Italy	Istituto Giannina Gaslini	Genova
Italy	Azienda Ospedaliera Universitaria "Federico II"	Napoli
Italy	Fondazione Policlinico Universitario Agostino Gemelli	Roma
Italy	IRCCS Ospedale Pediatrico Bambino Gesù	Roma
Italy	Oasi Maria SS	Troina
Spain	Hospital General Universitario Dr. Balmis	Alicante
Spain	Hospital General Universitario Gregorio Maranon-Instituto Provincial de Psiquiatria y Salud Mental	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Virgen de la Victoria	Malaga
Spain	Hospital Regional Universitario de Málaga - Hospital General	Málaga
Spain	Parc Taulí Sabadell Hospital Universitari	Sabadell
Spain	Hospital Universitario Virgen del Rocío	Sevilla
United States	Maimonides Medical Center	Brooklyn	New York
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	NYU Langone Hospital-Long Island	Mineola	New York
United States	Morgan Stanley Children's Hospital of NewYork-Presbyterian	New York	New York
United States	University of Utah School of Medicine	Salt Lake City	Utah
United States	Rady Children's Hospital-San Diego	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Gedeon Richter Plc.

Countries where clinical trial is conducted

United States,  Czechia,  France,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: Change from baseline in the 9-item Hyperphagia Questionnaire for Clinical Trials (HQ-CT)	The HQ-CT is a questionnaire designed to measure symptoms of food-related preoccupations, problems, and behaviors completed by the caregiver. The scale provides a composite value from 9 questions, each rated on a scale of 0 to 4 units (possible total score range: 0 to 36). Higher scores represent increased hyperphagia.	Part A: Baseline to Day 42
Primary	Part B: Change from baseline in the 9-item Hyperphagia Questionnaire for Clinical Trials (HQ-CT)	The HQ-CT is a questionnaire designed to measure symptoms of food-related preoccupations, problems, and behaviors completed by the caregiver. The scale provides a composite value from 9 questions, each rated on a scale of 0 to 4 units (possible total score range: 0 to 36). Higher scores represent increased hyperphagia.	Part B: Baseline to Day 105
Secondary	Part A and Part B: Change from baseline in the 9-item Hyperphagia Questionnaire for Clinical Trials (HQ-CT)	The HQ-CT is a questionnaire designed to measure symptoms of food-related preoccupations, problems, and behaviors completed by the caregiver. It consists of 9 items, with a 2-week recall period. The scale provides a composite value from 9 questions, each rated on a scale of 0 to 4 units (possible total score range: 0 to 36). Higher scores represent increased hyperphagia.	Part A: Baseline to Days 28, 56, 98 and 133; Part B: Baseline to Days 42, 70 and 119
Secondary	Part A and Part B: Change from baseline in Hyperphagia Questionnaire for Clinical Trials (HQ-CT) domain scores (drive and severity, self-directed behavior)	The HQ-CT is a questionnaire designed to measure symptoms of food-related preoccupations, problems, and behaviors completed by the caregiver. The scale provides a composite value from 9 questions, each rated on a scale of 0 to 4 units (possible total score range: 0 to 36). Higher scores represent increased hyperphagia.	Part A: Baseline to Days 28, 42, 56, 98 and 133; Part B: Baseline to Days 42, 70, 105 and 119
Secondary	Part A and Part B: Absolute change from baseline in body weight		Part A: Screening, Days 1, 14, 28, 42, 56, 98 and 133; Part B: Screening, Days 1, 14, 28, 42, 70, 105 and 119
Secondary	Part A and Part B: Percentage change from baseline in body weight		Part A: Screening, Days 1, 14, 28, 42, 56, 98 and 133; Part B: Screening, Days 1, 14, 28, 42, 70, 105 and 119
Secondary	Part A and Part B: Change from baseline in waist circumference		Part A: Screening, Days 1, 14, 28, 42, 56, 98 and 133; Part B: Screening, Days 1, 14, 28, 42, 70, 105 and 119
Secondary	Part A and Part B: Change from baseline in body mass index (BMI)		Part A: Screening, Days 1, 14, 28, 42, 56, 98 and 133; Part B: Screening, Days 1, 14, 28, 42, 70, 105 and 119
Secondary	Part A and Part B: Change from baseline in metabolic biomarkers measured from serum		Part A: Baseline to Day 42; Part B: Baseline to Days 42, 70 and 105
Secondary	Part A and Part B: Change from baseline in Clinical Global Impression-Severity (CGI-S)	The CGI-S rates overall symptom severity on a 4-point scale ranging from 1 (normal) to 7 (severely symptomatic), as assessed by the investigator.	Part A: Baseline to Days 28, 42 and 56; Part B: Baseline to Days 42, 70, 105 and 119
Secondary	Part A and Part B: Clinical Global Impression-Improvement (CGI-I)	The CGI-I is a single statement designed to assess the investigator's overall perception of change in the patient's condition across the course of the clinical trial. The CGI-I uses a 7-point response scale ranging from 1 (very much improved) to 7 (very much worse).	Part A: Days 28 and 42; Part B: Baseline to Days 42, 70 and 105
Secondary	Part A and Part B: Change from baseline in Caregiver Global Impression-Severity (CaGI-S)	The CaGI-S rates severity of the patient's food-related behavior assessed by the caregiver following a 4-point scale ranging from 0 (none) to 3 (severe).	Part A: Baseline to Days 2 and 42; Part B: Baseline to Days 42, 70 and 105
Secondary	Part A and Part B: Caregiver Global Impression-Change (CaGI-C)	The CaGI-C is a single item designed to assess the primary caregiver's overall perception of change in the patient's hyperphagia symptoms. Responses are rated using a 7-point scale ranging from 1 (much better) to 7 (much worse).	Part A: Days 28, 42, 56, 98 and 133; Part B: Days 42, 70, 105 and 119
Secondary	Part A and Part B: Change from baseline in Zarit Burden Interview-22 (ZBI-22)	The ZBI-22 is a self-reported questionnaire in which primary caregivers rate the level of burden currently experienced while taking care of the patient rated on a 5-point scale ranging from 0 (never) to 4 (nearly always).	Part A: Baseline to Day 42; Part B: Baseline to Day 105
Secondary	Part A and Part B: Safety - Incidence of treatment-emergent adverse events (TEAEs)		Part A: Screening thru study end; Up to 24 weeks; Part B: Screening to end of study; Up to 17 weeks
Secondary	Part A and Part B: Safety - Incidence of clinically significant findings in laboratory values	Clinical laboratory evaluations (hematology, clinical chemistry, coagulation and lipids, thyroid function test, and urinalysis)	Part A: Screening thru study end; Up to 24 weeks; Part B: Screening to end of study; Up to 17 weeks
Secondary	Part A and Part B: Safety - Incidence of clinically significant findings in vital signs	Vital signs measurements (body temperature, pulse rate, respiration rate, blood pressure [BP])	Part A: Screening thru study end; Up to 24 weeks; Part B: Screening to end of study; Up to 17 weeks
Secondary	Part A and Part B: Safety - Incidence of clinically significant findings in 12-lead electrocardiograms (ECGs)		Part A: Screening thru study end; Up to 24 weeks; Part B: Screening to end of study; Up to 17 weeks
Secondary	Part A and Part B: Safety - Incidence of clinically significant findings in Columbia-Suicide Severity Rating Scale (C-SSRS)	The C-SSRS is a clinician-rated instrument that captures the occurrence, severity, and frequency of suicidal ideation and/or behavior during the assessment period. The scale includes suggested questions to solicit the type of information needed to determine if suicidal ideation and/or behavior occurred.	Part A: Screening thru study end; Up to 24 weeks; Part B: Screening to end of study; Up to 17 weeks
Secondary	Part A and Part B: Safety - Incidence of clinically significant findings in laboratory values physical examinations		Part A: Screening thru study end; Up to 24 weeks; Part B: Screening to end of study; Up to 17 weeks
Secondary	Part B: Change from baseline in total body mass measured by Lunar dual-energy X-ray absorptiometry (iDXA)		Part B: Baseline to Day 105
Secondary	Part B: Change from baseline in lean body mass measured by Lunar dual-energy X-ray absorptiometry (iDXA)		Part B: Baseline to Day 105
Secondary	Part B: Change from baseline in total fat mass measured by Lunar dual-energy X-ray absorptiometry (iDXA)		Part B: Baseline to Day 105
Secondary	Part B: Change from baseline in visceral fat mass measured by Lunar dual-energy X-ray absorptiometry (iDXA)		Part B: Baseline to Day 105
Secondary	Part B: Change from baseline in subcutaneous fat mass measured by Lunar dual-energy X-ray absorptiometry (iDXA)		Part B: Baseline to Day 105