Efficacy and Safety Study of MYOBLOC in the Treatment of Sialorrhea in Pediatric Subjects

NCT05097079 | Withdrawn Phase 3 DMC FDA Drug

• 1 other identifier: SN-SIAL-302
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will evaluate the efficacy and safety of MYOBLOC for the treatment of chronic sialorrhea in pediatric subjects.

Conditions

Sialorrhea

Outcome Measures

Primary Outcomes (2)

• The change from baseline in the Unstimulated Saliva Flow Rate (USFR) at Week 4 post-injection.

  At each study visit, the subject's saliva is collected for at least 3 minutes and weighed (grams). The Unstimulated Saliva Flow Rate (USFR; grams/minute) for each visit is calculated for by dividing the 'total grams of saliva collected during the collection period' by the 'total minutes of the collection period. The USFR at Week 4 post-injection visit subtracted from the USFR at Baseline visit (prior to injection) yields the change from baseline USFR. A change from baseline USFR \<0 grams/minutes represents a better outcome.

  Baseline and Week 4

• The Clinical Global Impression of Change (CGI-C) score at Week 4 post-injection.

  The Clinical Global Impression of Change (CGI-C) scale is a single item clinician assessment of how much the subject's condition (sialorrhea) has improved, worsened or has not changed relative to subject's state at baseline prior to treatment (injection). The CGI-C is rated on a 7-point scale from 1 to 7, where 1 = "Very much improved", 2 = "Much improved", 3 = "Minimally improved", 4 = "No change", 5 = "Minimally worse", 6 = "Much worse", and 7 = "Very much worse". A CGI-C score \<4 represents a better outcome.

  Week 4

Secondary Outcomes (6)

• The Parent/Guardian Global Impression of Change (PGI-C) score at Week 4 post-injection.

  Week 4

• The change from baseline in the Unstimulated Saliva Flow Rate (USFR) at Weeks 2, 8 and 13 post-injection.

  Baseline and Weeks 2, 8 and 13

• The Clinical Global Impression of Change (CGI-C) score at Weeks 2, 8, and 13 post-injection.

  Weeks 2, 8 and 13

• The Parent/Guardian Global Impression of Change (PGI-C) score at Week 2, 8, and 13 post-injection.

  Weeks 2, 8, and 13

• The change from baseline in the Modified Teacher's Drooling Scale (mTDS) score at Week4 post injection.

  Baseline and Week 4

Study Arms (3)

MYOBLOC Low Dose

EXPERIMENTAL

MYOBLOC Low Dose will be administered as a single treatment via intraglandular injection (60 Units/kg)

Drug: MYOBLOC Low Dose

MYOBLOC High Dose

EXPERIMENTAL

MYOBLOC High Dose will be administered as a single treatment via intraglandular injection (100 units/kg)

Drug: MYOBLOC High Dose

Placebo

PLACEBO COMPARATOR

Volume-matched placebo will be administered as a single treatment via intraglandular injection

Drug: Placebo

Interventions

MYOBLOC Low Dose DRUG

Subjects assigned to the MYOBLOC Low Dose treatment group will be administered MYOBLOC (60 units/kg; maximum 1800 units) as a single treatment via intraglandular injection (5.0 units/kit per submandibular gland \[maximum 150 units\] and 25.0 units/kg per parotid gland \[maximum 750 units\])

Also known as: rimabotulinumtoxinB

MYOBLOC Low Dose

MYOBLOC High Dose DRUG

Subjects assigned to the MYOBLOC High Dose treatment group will be administered MYOBLOC (100 units/kg; maximum 3000 units) as a single treatment via intraglandular injection (25.0 units/kit per submandibular gland \[maximum 300 units\] and 40.0 units/kg per parotid gland \[maximum 1200 units\])

Also known as: rimabotulinumtoxinB

MYOBLOC High Dose

Placebo DRUG

Subjects assigned to the Placebo treatment group will be administered volume-matched placebo (1:1)

Also known as: PBO

Placebo

Eligibility Criteria

• Age: 3 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Written informed consent obtained from the subject's parent or legally authorized representative(s) (LAR)/guardian(s) in accordance with local laws and Institutional Review Board (IRB)/Independent Ethics Committee (IEC) requirements.
• Written minor assent obtained from the subject, as applicable and in accordance with local laws and IRB/IEC requirements.
• Male or female ages 3 to \< 17 years at the time of signing informed consent (and assent, if applicable) at Screening.
• Minimum weight of 10 kg at Screening and Baseline (prior to randomization).
• Chronic sialorrhea due to a neurological disorder (e.g., cerebral palsy (CP), or traumatic brain injury (TBI)) for at least 3 months prior to Screening.
• A mTDS score ≥ 5 at Screening and Baseline (prior to randomization).
• A minimum USFR of 0.2 g/min at Screening and Baseline (prior to randomization).
• Females of childbearing potential (FOCP) must be either sexually inactive (abstinent) or, if sexually active, must agree to use/practice one of the following acceptable methods of contraception beginning during screening period prior to baseline (randomization, injection), for the duration of the study, and 2 months after study completion:
• simultaneous use of male condom and intra-uterine contraceptive device placed during screening period prior to baseline (randomization, injection)
• barrier method: condom with spermicidal foam/gel/film/cream/suppository or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository;
• established use of oral, injected or implanted hormonal methods of contraception;
• surgically sterile male partner (e.g., vasectomized partner is sole partner). With approval by the Investigator, subjects' parents or legal guardians may select abstinence as a form of birth control if deemed more appropriate. For the purposes of this study, all females are considered to be of childbearing potential unless they are confirmed by the Investigator to be premenarchal, biologically sterile, or surgically sterile (e.g., hysterectomy with bilateral oophorectomy, tubal ligation).
• Subject and the subject's parent/LAR are willing and able to comply with scheduled visits, treatment plan, laboratory tests, home monitoring, and other study procedures.

You may not qualify if:

• FOCP subjects who are pregnant, lactating/breastfeeding and/or sexually active and not agreeing to use one of the acceptable birth control methods throughout the study.
• History of drug or alcohol abuse within 6 months before Screening.
• Treatment with an investigational drug, device, or biological agent within 30 days before Screening or while participating in this study.
• Major surgery (requiring general anesthesia) within 3 months before screening, or any anticipated or scheduled surgery during the study period (with or without general anesthesia).
• Aspiration pneumonia within 6 months before Screening.
• History of moderate dysphagia or severe dysphagia (defined as an inability to swallow liquids, solids or both without choking or medical intervention) within 6 months before screening. Subjects who require gastrostomy tube feeding are not excluded provided tube placement was at least 30 days prior to Baseline (Day 1; injection).
• Requires general anesthesia for study drug administration.
• Subjects must not receive nor have any plans to receive any other form of botulinum toxin treatment, other than the study drug (MYOBLOC), from the time that the informed consent is obtained until participation in the study is complete.
• History of lack of response to MYOBLOC.
• Any previous known or suspected hypersensitivity to botulinum toxins type A (BoNT/A) or B (BoNT/B) or to any of the MYOBLOC solution components.
• Oxygen saturation \< 95% on room air at Screening and Baseline (prior to randomization).
• Subjects taking medications with anticholinergic/antihistamine properties who have not been on a stable dose and regimen for at least 2 weeks before Day 1. The same dose and dosing regimen must be maintained through the Week 4 study visit.
• Diagnosed with Obstructive Sleep Apnea which requires nightly Continuous Positive Airway Pressure (CPAP) or Bi-level Positive Airway Pressure (BiPAP) therapy, such that subject has been receiving nightly therapy for at least 30 days.
• Current or recent treatment (exposure within 5 half-lives of screening) or treatment at any time during the study with aminoglycoside antibiotics, curare-like agents, other agents that interfere with neuromuscular function, or dopamine receptor blocking agents (e.g., clozapine).
• Prior surgery or irradiation in the head and neck to control sialorrhea (including salivary gland surgery or salivary gland irradiation) within 1 year before screening or planned during the study.

Sponsors & Collaborators

• Solstice Neurosciences, LLC, a subsidiary of MDD US Operations, LLC: lead

MeSH Terms

Conditions

Sialorrhea

Interventions

rimabotulinumtoxinB

Condition Hierarchy (Ancestors)

Salivary Gland Diseases; Mouth Diseases; Stomatognathic Diseases

Study Officials

• Jonathan Rubin, MD

  Supernus Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A Phase 3, multicenter, randomized, double-blind, placebo-controlled, single treatment study designed to assess the efficacy, safety, and tolerability of 2 dose levels of MYOBLOC compared to placebo for the treatment of chronic sialorrhea in pediatric subjects ages 3 to \< 17 years.

Study Record Dates

• First Submitted: October 18, 2021
• First Posted: October 27, 2021
• Study Start: November 1, 2021
• Primary Completion: May 1, 2023
• Study Completion: May 1, 2023
• Last Updated: September 19, 2024

Record last verified: 2024-09