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

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Prader-Willi Syndrome

Intervention / Treatment
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* Drug: RGH-706
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 17 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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RGH-706<br>Part A: Dose A once daily for 6 weeks Part B: Dose B, Dose C or Dose D once daily (depending on the randomized arm) for 13 weeks | Drug: RGH-706<br>* Capsules Oral administration<br>|
| Placebo Comparator: Placebo<br>Part A: Placebo once daily for 6 weeks Part B: Placebo once daily for 13 weeks | Drug: Placebo<br>* Capsules Oral administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prader-Willi Syndrome, Obesity, Hyperphagia control