Clinical trial NCT05322096: Study to Evaluate Efficacy, Safety, and Tolerability of RGH-706 in Prader-Willi Syndrome
Official title: A Randomized, Double-blind, Placebo-controlled, Multi-center, Phase 2 Study to Evaluate Efficacy, Safety, and Tolerability of RGH-706 in Prader-Willi Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prader-Willi Syndrome
Keywords: Prader-Willi Syndrome
Obesity
Hyperphagia control
Lead sponsor: Gedeon Richter Plc.
Sponsor class: INDUSTRY
First posted: 2022-04-11
Enrollment: 39
Sex: ALL
Minimum age (years): 17
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility 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

Primary outcomes:
measure: There are no Primary Outcome Measures
timeFrame: There are no Primary Outcome Measures
Secondary outcomes:
Other outcomes:
measure: Change from baseline in the 9-item Hyperphagia Questionnaire for Clinical Trials (HQ-CT)
timeFrame: Baseline to Day 42
measure: Change from baseline in the 9-item Hyperphagia Questionnaire for Clinical Trials (HQ-CT)
timeFrame: Baseline to Days 28, 56, 98 and 133
measure: Change from baseline in Hyperphagia Questionnaire for Clinical Trials (HQ-CT) domain scores (drive and severity, self-directed behavior)
timeFrame: Baseline to Days 28, 42, 56, 98 and 133
measure: Absolute change from baseline in body weight
timeFrame: Screening, Days 1, 14, 28, 42, 56, 98 and 133
measure: Percentage change from baseline in body weight
timeFrame: Screening, Days 1, 14, 28, 42, 56, 98 and 133
measure: Change from baseline in waist circumference
timeFrame: Screening, Days 1, 14, 28, 42, 56, 98 and 133
measure: Change from baseline in body mass index (BMI)
timeFrame: Screening, Days 1, 14, 28, 42, 56, 98 and 133
measure: Change from baseline in metabolic biomarkers measured from serum
timeFrame: Baseline to Day 42
measure: Change from baseline in Clinical Global Impression-Severity (CGI-S)
timeFrame: Baseline to Days 28, 42 and 56
measure: Clinical Global Impression-Improvement (CGI-I)
timeFrame: Days 28 and 42
measure: Change from baseline in Caregiver Global Impression-Severity (CaGI-S)
timeFrame: Baseline to Days 2 and 42
measure: Caregiver Global Impression-Change (CaGI-C)
timeFrame: Days 28, 42, 56, 98 and 133
measure: Change from baseline in Zarit Burden Interview-22 (ZBI-22)
timeFrame: Baseline to Day 42
measure: Safety - Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Screening thru study end; Up to 24 weeks
measure: Safety - Incidence of clinically significant findings in laboratory values
timeFrame: Screening thru study end; Up to 24 weeks
measure: Safety - Incidence of clinically significant findings in vital signs
timeFrame: Screening thru study end; Up to 24 weeks
measure: Safety - Incidence of clinically significant findings in 12-lead electrocardiograms (ECGs)
timeFrame: Screening thru study end; Up to 24 weeks
measure: Safety - Incidence of clinically significant findings in Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: Screening thru study end; Up to 24 weeks
measure: Safety - Incidence of clinically significant findings in laboratory values physical examinations
timeFrame: Screening thru study end; Up to 24 weeks
measure: PK Cohort - Individual plasma concentrations of RGH-706 and its metabolite desisopropyl RGH-706 maximum observed plasma concentration (Cmax)
timeFrame: Days 14, 42, 43, 44 and 46
measure: PK Cohort - Individual plasma concentrations of RGH-706 and its metabolite desisopropyl RGH-706 time of the maximum observed plasma concentration (Tmax)
timeFrame: Days 14, 42, 43, 44 and 46
measure: 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)
timeFrame: Days 14, 42, 43, 44 and 46
measure: PK Cohort - Individual plasma concentrations of RGH-706 and its metabolite desisopropyl RGH-706 minimum observed plasma concentration (Cmin)
timeFrame: Days 14, 42, 43, 44 and 46
measure: PK Cohort - Individual plasma concentrations of RGH-706 and its metabolite desisopropyl RGH-706 accumulation ratio (Rac)
timeFrame: Days 14, 42, 43, 44 and 46
Locations:
city: San Diego
country: United States
facility: Rady Children's Hospital-San Diego
state: California
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Brooklyn
country: United States
facility: Maimonides Medical Center
state: New York
city: Mineola
country: United States
facility: NYU Langone Hospital-Long Island
state: New York
city: New York
country: United States
facility: Morgan Stanley Children's Hospital of NewYork-Presbyterian
state: New York
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Prague
country: Czechia
facility: General University Hospital
city: Angers
country: France
facility: Centre Hospitalier Universitaire d'Angers
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon-Sud
city: Toulouse
country: France
facility: Hôpital Larrey
city: Firenze
country: Italy
facility: Azienda Ospedaliero-Universitaria Careggi
city: Genova
country: Italy
facility: Istituto Giannina Gaslini
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria "Federico II"
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli
city: Roma
country: Italy
facility: IRCCS Ospedale Pediatrico Bambino Gesù
city: Troina
country: Italy
facility: Oasi Maria SS
city: Alicante
country: Spain
facility: Hospital General Universitario Dr. Balmis
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon-Instituto Provincial de Psiquiatria y Salud Mental
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Malaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Málaga - Hospital General
city: Sabadell
country: Spain
facility: Parc Taulí Sabadell Hospital Universitari
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
Study officials:
References: