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

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

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).

Study Overview

• Status: Completed
• Conditions: Prader-Willi Syndrome
• Intervention / Treatment: Drug: RGH-706; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 2

Contacts and Locations

Study Locations

• Czechia
  • Prague, Czechia, 12808
    • General University Hospital
• France
  • Angers, France, 49933
    • Centre Hospitalier Universitaire d'Angers
  • Pierre-Bénite, France, 69495
    • Centre Hospitalier Lyon-Sud
  • Toulouse, France, 31059
    • Hôpital Larrey
• Italy
  • Firenze, Italy, 50139
    • Azienda Ospedaliero-Universitaria Careggi
  • Genova, Italy, 16147
    • Istituto Giannina Gaslini
  • Napoli, Italy, 80131
    • Azienda Ospedaliera Universitaria "Federico II"
  • Roma, Italy, 168
    • Fondazione Policlinico Universitario Agostino Gemelli
  • Roma, Italy, 50
    • IRCCS Ospedale Pediatrico Bambino Gesu
  • Troina, Italy, 94018
    • Oasi Maria SS
• Spain
  • Alicante, Spain, 03010
    • Hospital General Universitario Dr. Balmis
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28009
    • Hospital General Universitario Gregorio Maranon-Instituto Provincial de Psiquiatria y Salud Mental
  • Malaga, Spain, 29010
    • Hospital Universitario Virgen de la Victoria
  • Málaga, Spain, 29010
    • Hospital Regional Universitario de Malaga - Hospital General
  • Sabadell, Spain, 08208
    • Parc Taulí Sabadell Hospital Universitari
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio
• United States
  • California
    • San Diego, California, United States, 92123
      • Rady Children's Hospital-San Diego
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago
  • New York
    • Brooklyn, New York, United States, 11219
      • Maimonides Medical Center
    • Mineola, New York, United States, 11501
      • NYU Langone Hospital-Long Island
    • New York, New York, United States, 10032
      • Morgan Stanley Children's Hospital of NewYork-Presbyterian
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RGH-706; Dose A once daily for 6 weeks	Drug: RGH-706; Capsules Oral administration
Placebo Comparator: Placebo; Placebo once daily for 6 weeks	Drug: Placebo; Capsules Oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
There are no Primary Outcome Measures	There are no Primary Outcome Measures

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Part B: Change from baseline in total body mass measured by Lunar dual-energy X-ray absorptiometry (iDXA)		Part B: Baseline to Day 105
Part B: Change from baseline in lean body mass measured by Lunar dual-energy X-ray absorptiometry (iDXA)		Part B: Baseline to Day 105
Part B: Change from baseline in total fat mass measured by Lunar dual-energy X-ray absorptiometry (iDXA)		Part B: Baseline to Day 105
Part B: Change from baseline in visceral fat mass measured by Lunar dual-energy X-ray absorptiometry (iDXA)		Part B: Baseline to Day 105
Part B: Change from baseline in subcutaneous fat mass measured by Lunar dual-energy X-ray absorptiometry (iDXA)		Part B: Baseline to Day 105

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline to Day 42
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.	Baseline to Days 28, 56, 98 and 133
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.	Baseline to Days 28, 42, 56, 98 and 133
Absolute change from baseline in body weight		Screening, Days 1, 14, 28, 42, 56, 98 and 133
Percentage change from baseline in body weight		Screening, Days 1, 14, 28, 42, 56, 98 and 133
Change from baseline in waist circumference		Screening, Days 1, 14, 28, 42, 56, 98 and 133
Change from baseline in body mass index (BMI)		Screening, Days 1, 14, 28, 42, 56, 98 and 133
Change from baseline in metabolic biomarkers measured from serum		Baseline to Day 42
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.	Baseline to Days 28, 42 and 56
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).	Days 28 and 42
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).	Baseline to Days 2 and 42
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).	Days 28, 42, 56, 98 and 133
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).	Baseline to Day 42
Safety - Incidence of treatment-emergent adverse events (TEAEs)		Screening thru study end; Up to 24 weeks
Safety - Incidence of clinically significant findings in laboratory values	Clinical laboratory evaluations (hematology, clinical chemistry, coagulation and lipids, thyroid function test, and urinalysis)	Screening thru study end; Up to 24 weeks
Safety - Incidence of clinically significant findings in vital signs	Vital signs measurements (body temperature, pulse rate, respiration rate, blood pressure [BP])	Screening thru study end; Up to 24 weeks
Safety - Incidence of clinically significant findings in 12-lead electrocardiograms (ECGs)		Screening thru study end; Up to 24 weeks
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.	Screening thru study end; Up to 24 weeks
Safety - Incidence of clinically significant findings in laboratory values physical examinations		Screening thru study end; Up to 24 weeks
PK Cohort - Individual plasma concentrations of RGH-706 and its metabolite desisopropyl RGH-706 maximum observed plasma concentration (Cmax)		Days 14, 42, 43, 44 and 46
PK Cohort - Individual plasma concentrations of RGH-706 and its metabolite desisopropyl RGH-706 time of the maximum observed plasma concentration (Tmax)		Days 14, 42, 43, 44 and 46
PK Cohort - Individual plasma concentrations of RGH-706 and its metabolite desisopropyl RGH-706 area under the plasma concentration-time curve to the end of the dosing period (AUC0-24)		Days 14, 42, 43, 44 and 46
PK Cohort - Individual plasma concentrations of RGH-706 and its metabolite desisopropyl RGH-706 minimum observed plasma concentration (Cmin)		Days 14, 42, 43, 44 and 46
PK Cohort - Individual plasma concentrations of RGH-706 and its metabolite desisopropyl RGH-706 accumulation ratio (Rac)		Days 14, 42, 43, 44 and 46

Collaborators and Investigators

• Sponsor: Gedeon Richter Plc.

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2022
• Primary Completion (Actual): April 10, 2024
• Study Completion (Actual): April 10, 2024

Study Registration Dates

• First Submitted: March 25, 2022
• First Submitted That Met QC Criteria: April 4, 2022
• First Posted (Actual): April 11, 2022

Study Record Updates

• Last Update Posted (Actual): June 3, 2024
• Last Update Submitted That Met QC Criteria: May 30, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Obesity; Prader-Willi Syndrome; Hyperphagia control
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Congenital Abnormalities; Overnutrition; Nutrition Disorders; Overweight; Genetic Diseases, Inborn; Intellectual Disability; Abnormalities, Multiple; Chromosome Disorders; Obesity; Imprinting Disorders; Syndrome; Prader-Willi Syndrome
• Other Study ID Numbers: RGH-706-003; 2021-004262-35 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No