Prader-Willi Syndrome
Conditions
Keywords
Prader-Willi Syndrome, Obesity, Hyperphagia control
Brief 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).
Interventions
DRUGRGH-706
Capsules Oral administration
DRUGPlacebo
Capsules Oral administration
Sponsors
Gedeon Richter Plc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
17 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| There are no Primary Outcome Measures | There are no Primary Outcome Measures |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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 the 9-item Hyperphagia Questionnaire for Clinical Trials (HQ-CT) | Baseline to Day 42 | 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. |
| Change from baseline in Hyperphagia Questionnaire for Clinical Trials (HQ-CT) domain scores (drive and severity, self-directed behavior) | Baseline to Days 28, 42, 56, 98 and 133 | 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. |
| 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 Clinical Global Impression-Severity (CGI-S) | Baseline to Days 28, 42 and 56 | 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. |
| Clinical Global Impression-Improvement (CGI-I) | Days 28 and 42 | 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). |
| Change from baseline in Caregiver Global Impression-Severity (CaGI-S) | Baseline to Days 2 and 42 | 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). |
| Caregiver Global Impression-Change (CaGI-C) | Days 28, 42, 56, 98 and 133 | 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). |
| Change from baseline in Zarit Burden Interview-22 (ZBI-22) | Baseline to Day 42 | 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). |
| Change from baseline in waist circumference | Screening, Days 1, 14, 28, 42, 56, 98 and 133 | — |
| Safety - Incidence of clinically significant findings in laboratory values | Screening thru study end; Up to 24 weeks | Clinical laboratory evaluations (hematology, clinical chemistry, coagulation and lipids, thyroid function test, and urinalysis) |
| Safety - Incidence of clinically significant findings in vital signs | Screening thru study end; Up to 24 weeks | Vital signs measurements (body temperature, pulse rate, respiration rate, blood pressure \[BP\]) |
| 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) | Screening thru study end; Up to 24 weeks | 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. |
| 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 | — |
| Safety - Incidence of treatment-emergent adverse events (TEAEs) | Screening thru study end; Up to 24 weeks | — |
Countries
Czechia, France, Italy, Spain, United States
Outcome results
None listed