A 2-Part Study to Assess Efficacy, Safety and Tolerability of BMB-101 for the Treatment of Patients With Prader-Willi Syndrome.

Официальное название

A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study to Assess Efficacy, Safety and Tolerability of BMB-101 Oral Solution for the Treatment of Patients With Prader-Willi Syndrome (PWS)

Обзор

The goal of this clinical trial is to evaluate the safety and effects of a new drug called BMB-101 in people with Prader-Willi Syndrome (PWS). This study is designed as a multi-centre, double-blind, randomized, placebo controlled 2-part study with a blinded main phase followed up an open label extension phase.

Подробное описание

This study is designed as a 2-part study:

Part 1 is designed as a randomized phase, lasting up to 16 weeks. There will be a 4-week screening period. Following the screening period, participants will be randomized in a 1:1 ratio to either BMB-101 or placebo. Participants will enter into a weekly ascending Maximum Tolerated Dose (MTD) titration phase of 4 weeks followed by a maintenance phase of 8 weeks. There will be 5 clinic visits and 4 telephone visits.

Part 2 is designed to follow after the completion of the maintenance phase in Part 1. Participants at the discretion of the Investigator may elect to continue into an unblinded, expandable open label phase to receive BMB-101.

Participants who do not elect to continue into the open label phase will be tapered from assigned study treatment over 4 weeks following completion of the maintenance phase.

Вмешательства

• Препарат BMB-101
  Participants will receive weekly ascending oral doses of BMB-101(10 mg/mL) twice daily (BID) for 16 weeks. Doses will be based on weight (kg) and will initially start at 1.67 mg/kg. Doses may be titrated in 0.33 mg/kg increments based on tolerability up to a maximum dose of 2.0 mg/kg.
• Препарат Placebo
  Matched Placebo

Первичные конечные точки

• Change from Baseline in Hyperphagia Questionnaire for Clinical Trials scores over time in Prader-Willi Syndrome participants. [Срок оценки: 16 weeks]

Вторичные конечные точки (5)

• Change from Baseline in hyperphagia severity score as measured by the Caregiver Global Impression of Severity 7-point scale over time. [Срок оценки: 16 weeks]
• Change from Baseline in hyperphagia severity score as measured by the Clinician Global Impression of Severity 7-point scale over time. [Срок оценки: 16 weeks]
• Change from Baseline in severity of Prader-Willi Syndrome disease scores as measured by the Clinician Global Impression of Severity 7-point scale over time. [Срок оценки: 16 weeks]
• Change from Baseline in improvement of Prader-Willi Syndrome disease scores as measured by the Clinician Global Impression of Improvement 7-point scale over time. [Срок оценки: 16 weeks]
• Change from Baseline in Prader-Willi Syndrome correlated behavioral issues such as symptoms measured by the Prader-Willi Syndrome Profile on a 3-point scale over time. [Срок оценки: 16 weeks]

Критерии участия

Критерии включения

• Participant must be aged 18-65 years (both inclusive).
• Genetically confirmed diagnosis of Prader Willi Syndrome via standard DNA testing or other commonly approved methods.
• Willing and able to provide voluntary written informed consent, or have a Legally Authorized Representative who is able to provide consent.
• Moderate to severe hyperphagia as defined by a HQ-CT score ≥ 13 at time of randomization (Visit 3).
• If participant is receiving growth hormone, the subject must be on the same medication and stable dose for at least 90 days prior to Visit 1.
• Female participant of childbearing potential must have a negative urine pregnancy test at baseline. Participants of childbearing or child-fathering potential must be willing to use medically acceptable forms of birth control, which includes abstinence, while in this study and for 90 days after the last dose of study drug.
• Participant and/or caregiver has the ability to be compliant with study requirements, including visit schedule, diary completion and study drug accountability.
• If a caregiver assists in completion of questionnaires, the same caregiver is available to complete the questionnaires throughout the duration of the study.

Критерии исключения

• Participant has used metabolic agents known to affect appetite within 3 months of Visit 1.
• Participant use of psychotropic medications including SSRIs/SNRIs, monoamine-oxidase inhibitors, tricyclic antidepressants, other serotonergic agonists or antagonists (antipsychotics), and other agents which have known Serotonin Syndrome risk (e.g. mirtazapine) within 1 month of Visit 1.
• Participant has implementation of new food restrictions or new environmental restrictions within 1 month of Visit 1.
• Participant has participated in an interventional clinical trial of any Prader-Willi Syndrome agent within 3 months of Visit 1 or any other investigational agent within 1 month of Visit 1.
• Participant has current or past history of cardiovascular or cerebrovascular disease, such as cardiac valvulopathy, pulmonary hypertension, myocardial infarction or stroke, or clinically significant structural cardiac abnormality.
• Participant has moderate or severe hepatic impairment. Asymptomatic participants with mild hepatic impairment (elevated liver enzymes < 3x upper limit of normal (ULN) and/or elevated bilirubin <2x ULN) may be entered into the study after review and approval by the Medical Monitor in conjunction with the sponsor, in consideration of comorbidities and concomitant medications.
• Participant has severe renal impairment (estimated glomerular filtration rate <30mL/min/1.73m2).
• Participant has clinically significant ECG abnormality such as QTcF >450 msec (males) or >470 msec (females).
• Participant has a history of drug or alcohol abuse within the last 12 months or a positive urine drug screen.
• A current C-SSRS score of 4 or 5 at Visit 1 or history of suicide attempt at any time during the past year.
• Participant has a clinically significant condition or has had clinically relevant symptoms or a clinically significant illness in the 4 weeks prior to Visit 1, other than PWS, that would negatively impact study participation, collection of study data, evaluation of study endpoints or pose a risk to the participant, in the opinion of the Investigator.
• Participant is pregnant (determined by a positive urine pregnancy test) or lactating female.
• Any condition that is thought to be a degenerative neurological disease.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Австралия · 2 центра

• Royal Prince Alfred Hospital — Sydney
• Alfred Health — Melbourne

Идентификаторы

NCT: NCT07266324 · BMB-101-201

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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