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

S

Solstice Neurosciences, LLC, a subsidiary of MDD US Operations, LLC

Status and phase

Withdrawn
Phase 3

Conditions

Sialorrhea

Treatments

Drug: Placebo
Drug: MYOBLOC High Dose
Drug: MYOBLOC Low Dose

Study type

Interventional

Funder types

Industry

Identifiers

NCT05097079
SN-SIAL-302

Details and patient eligibility

About

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

Full description

This is a multicenter, randomized, double-blind, placebo-controlled, single treatment study designed to assess the efficacy, safety, and tolerability of 2 dose levels of MYOBLOC vs placebo for the treatment of chronic sialorrhea in pediatric subjects ages 3 to < 17 years. Eligible subjects will be randomized 1:1:1 to receive single treatment of the low dose of MYOBLOC (60 Units/kg), the high dose of MYOBLOC (100 Units/kg), or volume-matched placebo via intraglandular injection.

Sex

All

Ages

3 to 17 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  1. 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.

  2. Written minor assent obtained from the subject, as applicable and in accordance with local laws and IRB/IEC requirements.

  3. Male or female ages 3 to < 17 years at the time of signing informed consent (and assent, if applicable) at Screening.

  4. Minimum weight of 10 kg at Screening and Baseline (prior to randomization).

  5. 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.

  6. A mTDS score ≥ 5 at Screening and Baseline (prior to randomization).

  7. A minimum USFR of 0.2 g/min at Screening and Baseline (prior to randomization).

  8. 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:

    1. simultaneous use of male condom and intra-uterine contraceptive device placed during screening period prior to baseline (randomization, injection)
    2. 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;
    3. established use of oral, injected or implanted hormonal methods of contraception;
    4. 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).
  9. 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.

Exclusion criteria

  1. 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.

  2. History of drug or alcohol abuse within 6 months before Screening.

  3. Treatment with an investigational drug, device, or biological agent within 30 days before Screening or while participating in this study.

  4. 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).

  5. Aspiration pneumonia within 6 months before Screening.

  6. 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).

  7. Requires general anesthesia for study drug administration.

  8. Prior botulinum toxin type A (BoNT/A) or BoNT/B treatment for sialorrhea or cervical dystonia within 20 weeks before screening. Prior BoNT/A or BoNT/B treatment in other anatomical locations is not exclusionary, but must have occurred at least 12 weeks prior to screening. Prior toxin exposure must have been well tolerated and without any significant long-term side effects in cases of repeated prior exposure.

  9. 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.

  10. History of lack of response to MYOBLOC.

  11. 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.

  12. Oxygen saturation < 95% on room air at Screening and Baseline (prior to randomization).

  13. 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.

  14. 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.

  15. 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).

  16. Current treatment or treatment at any time during the study with Coumadin® (warfarin) or similar anti-coagulant medications. Anti-platelet medications are not specifically exclusionary.

  17. 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.

  18. Extremely poor dental and/or oral condition, including infection at injection site(s) that might preclude safe study participation according to the judgment of the Investigator.

  19. Has one or more screening clinical laboratory test values outside the reference range that, in the opinion of the Investigator, are clinical significant, or any of the following:

    1. Serum creatinine >1.5 times the upper limit of normal (ULN);
    2. Serum total bilirubin >1.5 times ULN;
    3. Serum alanine aminotransferase or aspartate aminotransferase >2 times ULN.
  20. Has any of the following cardiac findings at Screening:

    1. Abnormal ECG that is, in the Investigator's opinion/evaluation, clinically significant;
    2. PR interval > 150 msec (2-5 years old); > 170 msec (6-11 years old); or > 180 msec (12-17 years old)
    3. QRS interval > 80 msec (2-5 years old); or > 90 msec (6-17 years old)
    4. QTcF interval >450 msec (for males), or >470 msec (for females) (QT corrected using Fridericia's method);
    5. Second-or third-degree atrioventricular block;
    6. Any rhythm, other than sinus rhythm, that is interpreted or assessed by the Investigator to be clinically significant.
  21. Has received COVID-19 vaccine (single or 2nd dose) in the last 30 days prior to Screening.

  22. Chronic or current use of inhaled corticosteroids, short acting beta-agonists or any other medication to manage asthma or other lung conditions such as emphysema.

  23. Any other medical illness, condition, or clinical finding, including clinically significant abnormal laboratory values that in the opinion of the Investigator and/or the Sponsor, would put the subject at undue risk.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Quadruple Blind

0 participants in 3 patient groups, including a placebo group

MYOBLOC Low Dose
Experimental group
Description:
MYOBLOC Low Dose will be administered as a single treatment via intraglandular injection (60 Units/kg)
Treatment:
Drug: MYOBLOC Low Dose
MYOBLOC High Dose
Experimental group
Description:
MYOBLOC High Dose will be administered as a single treatment via intraglandular injection (100 units/kg)
Treatment:
Drug: MYOBLOC High Dose
Placebo
Placebo Comparator group
Description:
Volume-matched placebo will be administered as a single treatment via intraglandular injection
Treatment:
Drug: Placebo

Trial contacts and locations

0

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Central trial contact

Lubna Jamal, MD, MBA; Joseph T Hull, PhD

Data sourced from clinicaltrials.gov

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