Refractory Chronic Cough and Unexplained Chronic Cough
Conditions
Keywords
RCC, UCC, Refractory Chronic Cough, Unexplained Chronic Cough, SC0032
Brief summary
This is a randomized placebo-controlled, parallel-arm study to determine the safety and efficacy of SC0032 in participants with RCC
Detailed description
There are three parts to this study and an optional fourth part: 1. an optional Usability Sub-Study, 2. Part 1: Two Week Treatment (Run-In) Period, 3. Part 2:Three Week Treatment (Parallel Arm) Period and 4. Part 3: Four Week No Treatment (Follow-Up) Period, Participants completing the three primary parts of the study will attend four study visits. Participation in the optional Usability sub-study does not require any additional visits, see Figure 1. Trial Schema. Participants who do not meet criteria for Part 2, the Parallel Arm Period, at the end of Part 1, the Run-In period, will only be required to attend two study visits and will not receive an active treatment. Participants who discontinue the study prior to completion will be asked to complete an Early Termination Visit.
Interventions
COMBINATION_PRODUCTSC0032
Magnesium Chloride
DEVICEPlacebo
Sodium Chloride
Sponsors
Sensory Cloud, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Combination product SC0032 versus placebo.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Males and females between 18 and 80 years. 2. Capable of giving signed informed consent. 3. Diagnosed with RCC (including unexplained chronic cough) for at least 6 months. 4. At least 8 coughs per hour, 24-hour cough frequency during the 14-day Run-In Period. 5. Score ≥ 40 mm on cough severity VAS at Screening. 6. Normal FEV1/FVC ratio of greater than 70% at Screening 7. A negative test for COVID-19. 8. Women of child-bearing potential and men must agree to use a highly effective contraception method during the study and for at least 14 days after the last dose. 9. Willing to carry study-related equipment as required for the study (e.g. cough monitor, phone).
Exclusion criteria
1. Current smoker/vaper (all forms of smoking and inhaled substances, including cannabis/tobacco smoke and nicotine vapours) or individuals who have given up smoking within the past 6 months, or those with \>20 pack-year smoking history. 2. Diagnosis of Chronic Obstructive Pulmonary Disease (COPD), bronchiectasis, idiopathic pulmonary fibrosis, uncontrolled asthma or other serious pulmonary disease. 3. Respiratory tract infection within 4 weeks before screening. 4. History of malignancy in the last 5 years, unless it is a non-serious skin cancer. 5. History of moderate or severe alcohol or drug use disorder within the last 3 years. 6. Opioid use with in the 7 days prior to screening. 7. History of a positive serologic test for hepatitis B virus surface antigen, or hepatitis C virus. 8. Previous participation in a clinical trial in the last 30 days or 6-half half-lives of test drug activity. 9. Current participation in or completion of speech language therapy intervention therapy for chronic cough within 8 weeks prior to screening. 10. Use of Prohibited medications within 4 weeks prior to screening and at any time during the study: anti-tussive therapy, systemic corticosteroids, ACE inhibitors, opioids. 11. Gabapentin and pregabalin are prohibited unless they are being administered for treatment of a condition other than RCC and have been on a stable dose of that medication for at least 6 weeks prior to screening and plan to remain on that dose for the duration of the study. 12. Tricyclic antidepressants are prohibited unless they are being administered for treatment of a condition other than RCC and have been on a stable dose of that medication for at least 12 weeks prior to screening and plan to remain on that dose for the duration of the study. 13. Beta blockers are prohibited unless they are on a stable dose for at least 6 weeks prior to screening. 14. Use of dietary supplements containing magnesium for the duration of the study. 15. History of myocardial infarction or other cardiac disorders as follows: * History of any of the following within 6 months prior to screening, myocardial infarction, stroke or transient ischemic attack, coronary revascularization (PCI or CABG), or heart failure. * History of clinically significant arrhythmias, poorly controlled hypertension. * Any condition that, in the opinion of the investigator, places the participant at high risk for an acute cardiovascular event including but not limited to: angina symptomatic peripheral arterial disease, severe valvular heart disease, planned cardiovascular intervention or surgery during the study period, baseline QTc interval \>450 ms (men) or \>470 ms (women), or any clinically significant ECG abnormality as determined by the Investigator. 16. History of any clinically significant or psychiatric condition that, in the eyes of the Investigator or designee, would not be suitable for this study. Or if, in the eyes of the Investigator or designee may prove non-compliant to study procedures. 17. Spouses or other family members with a chronic cough in the household. 18. Living and working in an excessively loud workplace (e.g. building site).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in mean % change from baseline in 24-hour cough frequency using the mean of Days -8 to -2 for last 7 days of baseline vs the mean of Days 13-19 last 7 days of the treatment period, using the HYFE continuous cough monitor). | Day -8 to Day 19. | Linear mixed model with log-transformed daily cough frequency as response variable, fixed effect for treatment, and random effects for participants; fitted model yields point estimate and 95% CI estimate of placebo-adjusted treatment effect |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to onset of response based on median time (in days) from start of treatment to first day when mean treatment effect ≥30%, based on cumulative daily averages using the HYFE continuous cough monitor) from Day 1 to Day 20. | From Day 1 to Day 20 | Kaplan-Meier survival analysis to estimate median time to response (with 95% confidence intervals); log-rank test to compare response times of the treatment groups Cox proportional hazards model with adjustment for mean baseline cough frequency will yield a hazard ratio and 95% CIs. |
| Determine duration of response (≥30% reduction relative to baseline) from baseline (mean of Days -8 to -2) vs the Follow up period (mean of Days 22-28, 29-35, 36-42 and 43-49). | Day -8 to Day 49 | Linear mixed model with log-transformed daily cough frequency as response variable, fixed effect for treatment, and random effects for participants; fitted model yields point estimate and 95% CI estimate of placebo-adjusted treatment effect over the follow up period. The differences in the proportion of responders during each week of the follow up period will be evaluated using a Fisher's exact test. |
| Change in number of cough bouts per 24-hour period, defined using inter-cough gap thresholds of 2.0s, from Day -14 to -2 and Day 1 to Day 21. | From Day -14 to Day 21 | Linear mixed model with log-transformed daily bout frequency as response variable, fixed effect for treatment, and random effects for participants; fitted model yields point estimate and 95% CI estimate of placebo-adjusted treatment effect. |
| Change in Leicester Cough questionnaire (LCQ) score on Day 0 vs Day 21. A 19-item, patient-completed health-related quality of life (HRQoL) for chronic cough. Each item is rated on a 7-point Likert scale (1-7), with higher score indicates better QoL. | Day 0 to Day 21 | The change from baseline will be analysed using an Analysis of Covariance (ANCOVA) model. The model will include baseline measurement (Visit 2 - Day 0) as a covariate and Treatment as the main factor; and a Baseline\*Treatment interaction term will be investigated. Type III sums of squares will be used. The model will yield adjusted least-squares means for Placebo and SC0032, along with the placebo-SC0032 treatment difference with corresponding 95% confidence intervals. A p value will also be presented for the difference. |
| Change in Cough Severity Visual Analogue Scale (CS-VAS) score (0-100mm line anchored with "no cough" at 0 mm and "worst cough imaginable" at 100 mm) from Day 0 and Day 21. | Day 0 to Day 21 | The change from baseline will be analysed using an Analysis of Covariance (ANCOVA) model. The model will include baseline measurement (Visit 2) as a covariate and Treatment as the main factor; and a Baseline\*Treatment interaction term will be investigated. Type III sums of squares will be used. The model will yield adjusted least-squares means for Placebo and SC0032, along with the placebo-SC0032 treatment difference with corresponding 95% confidence intervals. A p value will also be presented for the difference. |
| Change in Patient Global Impression of Severity 5-point score (PGI-S) score from Day 0 and Day 21. Response options typically range from "None" to "Severe", with higher scores indicating greater symptom severity. | Day 0 to Day 21 | The distribution of PGI-S at Visit 3 (Day 21) between Placebo and SC0032 will be compared using a Cochran-Mantel-Haenszel test. An ordered (proportional odds) logistic regression model will be used to quantify treatment effects and estimate odds ratios (at Visit 3, adjusted for PGIS score at Visit 2 (Day 0) ) with 95% confidence intervals. |
| Change in categorical Patient Global Impression of Change (PGI-C) score from Day 0 and Day 21 analyzed as the proportion of participants achieving improvement on the 7-point scale. Response options range from "Very much improved" to "Very much worse." | Day 0 to Day 21 | The difference in proportion of participants achieving improvement will be analysed using a Fisher's exact test (or CMH if appropriate). A binary logistic regression model (or ordinal equivalent) will be used to quantify treatment effects and estimate odds ratios with 95% confidence intervals. |
| Change in Newcastle Laryngeal Hypersensitivity Questionnaire (LHQ) score from Day 0 and Day 21. A 14-item tool measuring subjective laryngeal sensory symptoms. Items are rated on a 7-point Likert scale, with lower scores indicating greater severity. | Day 0 to Day 21 | The change from baseline will be analysed using an Analysis of Covariance (ANCOVA) model. The model will include baseline measurement (Visit 2) as a covariate and Treatment as the main factor; and a Baseline\*Treatment interaction term will be investigated. Type III sums of squares will be used. The model will yield adjusted least-squares means for Placebo and SC0032, along with the placebo-SC0032 treatment difference with corresponding 95% confidence intervals. A p value will also be presented for the difference. |
| Change in mean daily cough from Day -8 to -2 vs Day 13-19 in Daily Cough Numeric Rating Scale (CS-NRS), an 11-point PRO rating severity of their cough over the past 24 hours. The scale ranges from 0 ("no cough") to 10 ("worst possible cough"). | Day -8 to Day 19 | Linear mixed model as per Item 1 (primary endpoint). |
| Report incidence of treatment-emergent adverse events (TEAEs). | Day -14 to Day 49 | Descriptive summary of incidence of treatment-emergent adverse events by treatment according to SOC and Preferred Term; n (%) frequency for duration of study. |
| Report the severity of TEAEs. | Day -14 to Day 49 | Descriptive summary of severity (number and % of mild, moderate, or severe) of treatment-emergent adverse events by treatment for duration of study according to SOC and Preferred Term; n (%) frequency. |
| Change from in FEV₁ and FVC from Day -14 to Day 49 by treatment group. | Day -14 to Day 49 | Descriptive change distributions by treatment group. |
| Report number and % of participants with ≥1 serious adverse event (SAE) for duration of study. | Day -14 to Day 49 | Descriptive summary by treatment according to SOC and Preferred Term; n (%) frequency. |
| Difference in mean % change from baseline in 24-hour cough frequency. The mean of Days -8 to -2 (baseline) vs the mean of Days 1-7 and 8-12 (Parallel Arm period). | Day -8 to Day 12 | The same model used in the primary objective (Item 1) will be applied. |
| Determine the duration of response of SC0032 vs placebo by identifying the last week post-treatment when the mean treatment effect remains ≥20% reduction and ≥50% reduction. | Day -8 to Day 49 | Difference in mean % change in cough frequency between Day 22-28, 29-35, 36-42, 43-49 (Follow-up Period) and mean % change in cough frequency for Day -8 to -2 (baseline), SC0032 vs placebo. Descriptive and inferential comparison (as per item 3; for ≥20% reduction and ≥50% reduction thresholds. |
| Define time to onset of effect based on cough bouts analyzed as per Objective 2 ((≥30% reduction), time course of treatment as per Objective 3 (baseline (mean of Days -8 to -2) vs the Follow up period (mean of Days 22-28, 29-35, 36-42 and 43-49). | Day -8 to Day 49 | Time to onset will be analysed as per Objective 2, time course of treatment as per Objective 3 and the cough to bout ratio will be analysed using a linear mixed model (as per the primary). |
| Change in number, duration, and coughs per bout across definitions using linear mixed model with treatment group as a fixed effect, study day as a repeated-measure and random effects for participants between Day -14 to -2 and Day 1 to Day 21. | Day -14 to Day 21 | Compare number, duration, and coughs per bout across definitions using linear mixed model with treatment group as a fixed effect, study day as a repeated-measure and random effects for participants. |
| Change in PRO's (CS-VAS, PGI-S, LCQ, LHQ) from Day -14 to Day 0 and Day 21 to Day 49. | Day -14 to Day 49 | Descriptive summaries and change from Visit 1 (Day -14) to Visit 2 (Day 0) and from Visit 3 (Day 21) to Visit 4 (Day 49). All ANCOVAs as per Item 5. Except PGI-S which will be analyzed as per Item 7, along with descriptive summaries. |
| The proportion of participants with a clinically meaningful change in PGI-C at Visit 4 -Day 49. | Day -14 to Day 49 | Descriptive summaries of actual values at Visit 4 (Day 49) by treatment group, as per Item 8. |
Countries
United Kingdom
Outcome results
None listed