HYP01: Guanfacine for Hyperactivity in Children With Down Syndrome (HYPEbeGONE_DS)

Sponsor

Rachel G. Greenberg, MD, MB, MHS (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06042257

Collaborator

The Emmes Company, LLC (Industry), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The purpose of this study is to determine efficacy of guanfacine immediate release (GIR) for the treatment of hyperactivity/impulsivity and inattention in children 6-12 years of age with Down syndrome (DS) after 8 weeks of treatment.

Condition or Disease	Intervention/Treatment	Phase
Hyperactivity in Children With Down Syndrome Impulsivity in Children With Down Syndrome	Drug: Guanfacine Hydrochloride Immediate Release Drug: Placebo	Phase 2

Detailed Description

This is a randomized, double-blind, placebo-controlled flexibly dosed trial of guanfacine immediate release (GIR) in children with Down syndrome (DS) and symptoms of hyperactivity, inattention, and impulsivity. Participants will undergo a screening period of up to 29 days. Eligible participants meeting study criteria will be randomized 2:1 GIR or placebo. There are a total of up to 4 in person visits (screening, baseline, at Week 4, and at Week 8). Participants will receive GIR or placebo for up to 8 weeks. Weekly dose escalation will be determined via a telephone assessment at Weeks 1-3 and Weeks 4-7. Unmasking of participant and site staff will occur at the week 8, in-person visit. After unmasking, participants who were randomized to receive GIR will be given the option to 1) remain on GIR and to transition to open-label GIR per standard of care or 2) taper off of GIR. A Telephone Safety Assessment will be conducted for all participants, at 5 (+2) days after final study product administration. Blood specimens will be collected at the Week 4 and Week 8 visits for Pharmacokinetic (PK) analyses and lab assessments. Participants will be asked to keep a daily study drug diary and will complete study measures at screening/baseline, Week 4 and Week 8.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Participants will be randomized 2:1 to GIR or placebo.Participants will be randomized 2:1 to GIR or placebo.

Masking:

Triple (Participant, Care Provider, Investigator)

Masking Description:

A masked investigational pharmacist or designee will dispense study product according to randomization treatment assignments. All other site staff as well as participants and parents/legal guardians will also be masked for up to 8 weeks while the study participant is receiving study product. Participants, parents/legal guardians, site staff, and study administrators will be unmasked at the 8 week study visit. Emergency unmasking may occur at any time throughout the study in the event that knowledge of the actual treatment is absolutely essential for further management of the participant.

Primary Purpose:

Treatment

Official Title:

Guanfacine for Hyperactivity in Children With Down Syndrome (HYPEbeGONE_DS)

Anticipated Study Start Date :

Nov 1, 2023

Anticipated Primary Completion Date :

Nov 1, 2025

Anticipated Study Completion Date :

Feb 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Guanfacine Hydrochloride Immediate Release Eligible participants will receive GIR for up to 8 weeks. The treatment period will consist of study product administration from day 0 through day 56 with a masked dose-escalation period from day 0 through day 49.	Drug: Guanfacine Hydrochloride Immediate Release 0.5 mg capsules
Placebo Comparator: Placebo Eligible participants will receive Placebo for up to 8 weeks.The treatment period will consist of study product administration from day 0 through day 56 with a masked dose-escalation period from day 0 through day 49.	Drug: Placebo Matching placebo capsule

Arm

Intervention/Treatment

Active Comparator: Guanfacine Hydrochloride Immediate Release

Eligible participants will receive GIR for up to 8 weeks. The treatment period will consist of study product administration from day 0 through day 56 with a masked dose-escalation period from day 0 through day 49.

Drug: Guanfacine Hydrochloride Immediate Release

0.5 mg capsules

Placebo Comparator: Placebo

Eligible participants will receive Placebo for up to 8 weeks.The treatment period will consist of study product administration from day 0 through day 56 with a masked dose-escalation period from day 0 through day 49.

Drug: Placebo

Matching placebo capsule

Outcome Measures

Primary Outcome Measures

Change in parent-rated ABC-H (Aberrant Behavior Checklist-Hyperactivity) subscale core [Baseline to Week 8]
Change from baseline to Week 8 of the ABC-H subscale score. The ABC-H is a subscale of the ABC. Each of the 16 items is scored as 0 (never a problem), 1 (slight problem), 2 (moderately serious problem), or 3 (severe problem). The total score range is 0 to 48, where a higher score indicates endorsement of greater hyperactivity. Rating based on patient's behavior in last 4 weeks.

Secondary Outcome Measures

Change in parent-rated ABC-H (Aberrant Behavior Checklist-Hyperactivity) subscale core [Baseline to Week 4]
Change from baseline to Week 4 of the ABC-H subscale score. The ABC-H is a subscale of the ABC. Each of the 16 items is scored as 0 (never a problem), 1 (slight problem), 2 (moderately serious problem), or 3 (severe problem). The total score range is 0 to 48, where a higher score indicates endorsement of greater hyperactivity. Rating based on patient's behavior in last 4 weeks.
Proportion of participants with a CGI-I (Clinical Global Impression-Improvement) score of 2 or better at Week 4 [Baseline to Week 4]
CGI-I specific to hyperactivity, inattention and impulsivity behaviors. The CGI-I is a seven-point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. 1 = Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 5 = Minimally worse, 6 = Much worse, 7 = Very much worse.
Proportion of participants with a CGI-I (Clinical Global Impression-Improvement) score of 2 or better at Week 8 [Baseline to Week 8]
CGI-I specific to hyperactivity, inattention and impulsivity behaviors. The CGI-I is a seven-point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. 1 = Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 5 = Minimally worse, 6 = Much worse, 7 = Very much worse.
Safety of GIR (guanfacine immediate release) [Baseline through Week 8]
Number of participants with adverse events (AEs), serious adverse events (SAEs), or events of special interest (ESIs).

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Years to 12 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion:

Parent/Legal Guardian can understand the consent process and is willing to provide informed consent/HIPAA authorization prior to the conduct of any study-related procedures. When applicable, the minor participant is willing to provide assent.
Participant has clinical diagnosis of non-mosaic DS.
Participant is between 6 and 12 years of age (inclusive) at time of consent.
Participant weight is ≥ 25 kg.
Participant has clinically significant symptoms of hyperactivity, inattention and impulsivity manifested as minimum scores of the following rating scales within 30 days of randomization:
A minimum score of 18 on the parent-reported ABC-H subscale, AND
A minimum score of moderate or greater (≥ 4) on the clinician reported Clinical Global Impression Severity (CGI-S) score specific to hyperactivity, inattention and impulsivity behaviors.
Participant has co-morbid medical screening and clearance to proceed with a non-stimulant medication trial with GIR within 30 days of randomization.
Participant is willing and able to comply with study procedures, including adherence to medication dosing schedule.

Exclusion:

Participant has received guanfacine (any formulation) within 30 days of randomization.
Participant has received any of the following concomitant medication classes within 30 days of randomization:
Strong CYP3A4 inhibitors (e.g., boceprevir, clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, and voriconazole)
Strong CYP3A4 inducers (e.g., avasimibe, carbamazepine, phenytoin, rifampin, and St. John's wort)
Participant has a psychiatric comorbidity, such as major depressive disorder, bipolar disorder, obsessive-compulsive disorder, or a psychotic disorder, that requires a pharmacological treatment other than guanfacine
For participants ≥ 8 years old at the time of consent, participant has a history of suicidality or positive screen on Ask Suicide-Screening Questions (asQ) Tool.
Participant is currently in or plans to participate in another interventional study.
Participant has a known hypersensitivity to guanfacine.
Participant has had a previous guanfacine treatment failure, as determined by their primary treating physician.
Participant has had a seizure within the last 6 months.
Participant has had a change in their anti-convulsant dose within the last 4 weeks.
Participant has a cardiac-related condition including:
Significant symptomatic bradycardia;
2nd degree or 3rd degree (complete) heart block;
Baseline heart rate (HR) or systolic blood pressure (BP) > 2 standard deviations (SD) below mean for age as determined by medical examination;
History of aborted sudden cardiac death, unexplained syncope or near syncope, or historical use of a pacemaker as determined by medical history will require clearance by cardiology prior to enrollment;
Known history of congenital heart disease which requires ongoing care for monitoring or management will require clearance by cardiology prior to enrollment.
Participant has a history of untreated severe obstructive sleep apnea defined as obstructive apnea hypopnea index (OAHI) ≥ 10 events per hour or aortic regurgitation (AR). Participants with an OAHI index > 10/hr are eligible if managed with continuous positive airway pressure (CPAP).
Participant has untreated thyroid disease.
Participant has a known hepatic impairment defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2x the upper limit of normal (ULN) for age.
Participant has known impending or renal failure defined as:
Anuria diagnosed within 12 hours prior to enrollment;
Requiring renal replacement therapy.
Participant is pregnant.
Participant has any condition which would make the participant, in the opinion of the investigator, unsuitable for the study.