Open-Label and Single-Arm Study of MYOBLOC® in the Treatment of Troublesome Sialorrhea in Adults

Study Overview
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Brief Summary
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Multicenter, open-label, outpatient study of the safety and effectiveness of repeated doses of MYOBLOC over a 1-year duration in adult subjects with troublesome sialorrhea.

Detailed Description
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Multicenter, open-label, outpatient study of the safety and effectiveness of repeated doses of MYOBLOC over a 1-year duration in adult subjects with troublesome sialorrhea. The primary goal is to determine the long-term safety and tolerability of MYOBLOC (administered intraglandularly as single total dose of 3,500 Units) treatments every 13 weeks over a maximum possible duration of 1 year in adult subjects with troublesome sialorrhea. The secondary goal is to assess the magnitude of therapeutic response of MYOBLOC (administered intraglandularly as a single total dose of 3,500 Units) using effectiveness assessments performed at intervals after treatments every 13 weeks over a maximum possible duration of 1 year.

Official Title
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A Phase 3, Long-Term, Open-Label and Single-Arm Study of MYOBLOC® in the Treatment of Troublesome Sialorrhea in Adult Subjects

Conditions
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Sialorrhea

Intervention / Treatment
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* Drug: MYOBLOC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Seeking treatment for troublesome sialorrhea for at least 3 months that is occurring secondary to any disorder or related to any cause, including, but not limited to, Parkinson's Disease (PD), adult cerebral palsy, amyotrophic lateral sclerosis (ALS), stroke, traumatic brain injury, oral cancer, and side effects of other medications. Able to read and provide written informed consent before enrollment into the study, or the subject's caregiver (Legally Authorized Representative) can provide written informed consent. Male or female, 18 to 85 years of age (inclusive). Minimum unstimulated salivary flow rate of 0.2 g/min at screening Minimum Investigator's Drooling Frequency and Severity Scale (DFSS) score of 4 at screening. Ability and availability to participate in the study for up to 1 year (ALS subjects: ability and availability to participate in the study for at least 6 months), based on overall health of the subject and disease prognosis Exclusion Criteria: A moderate to high risk of aspiration will exclude participation in this study. Subjects whose risk of aspiration are judged by the Investigator to be satisfactorily controlled by placement of PEG tube or G-tube for nutritional support are eligible to participate. Respiratory forced vital capacity (FVC) of <20% of predicted Prior botulinum toxin type A or B treatment in the salivary gland(s) identified for treatment in this study within 24 weeks before screening. Prior botulinum toxin type A or B treatment into other anatomical regions not selected for treatment in this study is not exclusionary, but must have occurred at least 12 weeks before screening Subjects should be excluded if, in the Investigator's opinion, the subject failed to respond to previous treatment with botulinum toxin. Subjects should not receive nor have any plans for receiving any botulinum toxin treatment, other than the study drug (MYOBLOC), during the entire course of the study (from the point the informed consent is signed until subject's participation is complete). Concomitant use, or exposure within 5 half-lives of screening, of aminoglycoside antibiotics, curare-like agents, or other agents that interfere with neuromuscular function Prior salivary gland surgery 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 Evidence of any clinically significant neurologic disease Pregnancy or lactation Anticipated or scheduled surgery during the study period. A PEG tube/G tube may be placed for nutritional support at any time during the study and will not exclude the subject from continued study participation. Major surgery (requiring general anesthesia, except PEG tube/G tube placement ) within the previous 6 months before screening. Current infection at the sialorrhea treatment injection site(s) History of drug or alcohol abuse currently or within the previous 6 months Participation in another clinical drug, device, or biological agent study within 30 days of screening or while participating in this study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MYOBLOC Injection<br>After a screening period (up to 21 days), subjects who satisfy all eligibility criteria may receive single dose injections over the course of 1 year. | Drug: MYOBLOC<br>* After a screening period (up to 21 days), subjects who satisfy all eligibility criteria may receive single dose injections of 3,500 Units of MYOBLOC every 13 weeks (±2 weeks) for a total of 4 treatments via injections into the submandibular and parotid glands. Subjects will undergo safety and effectiveness assessments at Weeks 4, 8, 13, 17, 26, 30, 39, 43, and 52, and telephone follow up will occur at Weeks 21, 34, and 47<br>* Other names: botulinum toxin type B;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence, Seriousness, Severity, and Causality Assessment of Treatment Emergent Adverse Events (TEAE) | TEAEs Related to Study Medication include TEAEs classified as Possibly, Probably and Definitely Related. Treatment Session (TS) | Visits at Weeks 4 and 13 combined for each TS; including Visit at Week 8 for TS1 | 
| Occurrence of Adverse Events of Special Interest (AESI) | Treatment Session (TS) AESI includes: Aspiration, Aspirational pneumonia, Choking and Dysphagia. | Visits at Weeks 4 and 13 combined for each TS; including Visit at Week 8 for TS1 | 
| Columbia Suicide Rating Scale (C-SSRS): Suicidal Ideation, Behavior Scores and Intensity Scores | Participants Analyzed does not match the Participant Flow because one participant discontinued prior to the first post-injection visit. Per protocol participants were only required to complete two treatment sessions with a maximum of 4 treatment sessions allowed. All subjects received 3500 U doses except for 13 subjects who had decreased doses at Treatment Session 2 and/or 3 (2500 U to 3000 U). | Baseline (Day 1) of each TS to the following: TS1 Visits at Weeks 4, 8, 13; TS2-4 Visits at Weeks 4, 13 | 
| Occurrence of Dental Adverse Events | Treatment Session (TS) | Visits at Weeks 4 and 13 combined for each TS; including Visit at Week 8 for TS1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Unstimulated Salivary Flow Rate (USFR): Treatment Sessions 1-4 | For Treatment Sessions 2-4, the change from baseline is calculated using the Week 13 value from the previous Treatment Session as the new baseline. Week 8 was only assessed in Treatment Session 1. Treatment Session (TS) Participants Analyzed does not match the Participant Flow because patient data was not always captured for each endpoint at every visit. | Baseline (Day 1) of each TS to the following: TS1 Visits at Weeks 4, 8, 13; TS2-4 Visits at Weeks 4, 13 | 
| Change From Baseline in Clinical Global Impression of Severity (CGI-S) | CGI-S will be used to record the severity of illness (sialorrhea) on a 7-point scale ranging from a score of 1, normal to a score of 7, among the most extremely ill patients. Treatment Session (TS) Participants Analyzed does not match the Participant Flow because participant discontinued prior to the first post-injection visit. | Baseline (Day 1) of each TS to the following: TS1 Visits at Weeks 4, 8, 13; TS2-4 Visits at Weeks 4, 13 | 
| Clinical Global Impression of Change (CGI-C) | CGI-C will be used to record change or improvement of illness (sialorrhea) on a 7-point scale ranging from a score of 1, very much improved to a score of 7, very much worse. Participants Analyzed does not match the Participant Flow because participant discontinued prior to the first post-injection visit. Treatment Session (TS) | TS1 Visits at Weeks 4, 8, 13; TS2-4 Visits at Weeks 4, 13 | 
| Change From Baseline in Drooling Frequency and Severity Scale Performed by Trained Assessor (DFSS-I) | The DFSS will be used to assess the frequency and severity of drooling on a 5-point scale ranging from a score of 1, dry never drools to a score of 5, profuse clothing hands tray objects become wet. Drooling frequency will be assessed on a 4-point scale ranging from a score of 1, never drools to a score of 4, constantly drools. Treatment Session (TS) Participants Analyzed does not match the Participant Flow because participant discontinued prior to the first post-injection visit. The severity score and frequency score are summed together to create the DFSS total score (range 2-9). A decrease from baseline indicates improvement. | Baseline (Day 1) of each TS to the following: TS1 Visits at Weeks 4, 8, 13; TS2-4 Visits at Weeks 4, 13 | 
| Change From Baseline in Drooling Frequency and Severity Scale Performed by Subject (DFSS-S) | The DFSS will be used to assess the frequency and severity of drooling on a 5-point scale ranging from a score of 1, dry never drools to a score of 5, profuse clothing hands tray objects become wet. Drooling frequency will be assessed on a 4-point scale ranging from a score of 1, never drools to a score of 4, constantly drools. Treatment Session (TS) Participants Analyzed does not match the Participant Flow because patient data was not always captured for each endpoint at every visit. The severity score and frequency score are summed together to create the DFSS total score (range 2 -9). A decrease from baseline indicates improvement. | Baseline (Day 1) of each TS to the following: TS1 Visits at Weeks 4, 8, 13; TS2-4 Visits at Weeks 4, 13 | 
| Change From Baseline in Patient Global Impression of Severity (PGI-S) | The PGI-S scale will be used by the subject to rate the severity of his/her illness (sialorrhea) on an 7-point scale ranging from a score of 1, normal to a score of 7, among the most extremely ill. Treatment Session (TS) Participants Analyzed does not match the Participant Flow because participant discontinued prior to the first post-injection visit. | Baseline (Day 1) of each TS to the following: TS1 Visits at Weeks 4, 8, 13; TS2-4 Visits at Weeks 4, 13 | 
| Patient Global Impression of Change (PGI-C) | The PGI-C scale will be used by the subject to rate the change in symptoms of his/her illness (sialorrhea) on an 7-point scale ranging from a score of 1, very much improved to a score of 7, very much worse. Treatment Session (TS) Participants Analyzed does not match the Participant Flow because participant discontinued prior to the first post-injection visit. | TS1 Visits at Weeks 4, 8, 13; TS2-4 Visits at Weeks 4, 13 | 
| Change From Baseline in Drooling Impact Score (DIS) | The DIS is a 10-item questionnaire with each item rated by the subject to evaluate the impact of sialorrhea on daily activities (e.g., speech, social activities). Treatment Session (TS) Participants Analyzed does not match the Participant Flow because patient data was not always captured for each endpoint at every visit. Subject is requested to compare their current status to their last study visit using a 4-point scale ranging from a score of 1, not at all to a score of 4, very much. The DIS total score ranges from 10 to 40. A negative change from baseline indicates a positive clinical outcome. | Baseline (Day 1) of each TS to the following: TS1 Visits at Weeks 4, 8, 13; TS2-4 Visits at Weeks 4, 13 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cerebral Palsy, ALS, Stroke, Neuroleptics