A Study to Evaluate Safety and Efficacy of BOTOX in Adults With Moderate COPD

• ClinicalTrials.gov Identifier: NCT06003049
• Recruitment Status: Active, not recruiting
• First Posted: August 21, 2023
• Last Update Posted: May 10, 2024
• Sponsor: RMW Testing
• Information provided by (Responsible Party): RMW Testing

Study Description

Brief Summary:

The aim of this clinical trial to determine the safety and effectiveness of treating the COPD symptoms with subcutaneous BOTOX injections in participants with moderate COPD.

Condition or disease	Intervention/treatment	Phase
COPD	Drug: OnabotulinumtoxinA; Other: Placebo	Phase 2

Detailed Description:

This is a prospective, double-blind, randomized, placebo-controlled, investigator-initiated clinical trial to assess the safety, tolerability, and efficacy using an approved drug, BOTOX, in moderate COPD participants.

Forty participants with moderate COPD, defined as mMRC Dyspnea Scale scores of grades 2 or 3 and CAT scores of 12 to 20, will be included. If eligibility criteria are met, subjects will be randomized to either the treatment arm (BOTOX) or placebo, treated on day one and observed for 90 days for safety and efficacy.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment

Intervention Model Description

This is an Investigator-initiated a clinical trial to determine the safety and preliminary efficacy of subcutaneous injections of BOTOX in participants with moderate COPD.

Participants will be treated with either one series of subcutaneous injections of BOTOX or of normal saline solution in the back in the T-1 to T-5 dermatome regions as indicated in Appendix A.

Participants' COPD status will be measured using the COPD Assessment Test (CAT), Pulmonary Function Test (Spirometry), and 6 Minute Walk Test (6MWT).

• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Masking Description: Double-blind study
• Primary Purpose: Treatment
• Official Title: An Investigator-Initiated, Single Center, Prospective, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate Safety and Efficacy of OnabotulinumtoxinA (BOTOX®) in Adults With Moderate Chronic Obstructive Pulmonary Disease (COPD)
• Actual Study Start Date: October 1, 2023
• Estimated Primary Completion Date: July 12, 2024
• Estimated Study Completion Date: July 12, 2024

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Treatment Arm; OnabotulinumtoxinA	Drug: OnabotulinumtoxinA; BOTOX injection series; Other Name: BOTOX
Placebo Comparator: Placebo Arm; Normal saline	Other: Placebo; Placebo injection series

Outcome Measures

Primary Outcome Measures :

1. CAT (Average) [ Time Frame: 28 days ]
   The COPD Assessment Test (CAT) is assessed to capture the health status. The total score ranges from 0 to 40 points. Average change in CAT score over 28 days between treatment arms with a higher scores indicating a more significant change in health status.

Secondary Outcome Measures :

1. CAT (Change in Units) [ Time Frame: 28 days ]
   The COPD Assessment Test (CAT) is assessed to capture the health status. The total score ranges from 0 to 40 points. Portion of participants with a change in score of 2 or greater are indicating a change health status between baseline and day 28 follow-up assessment.
2. FEV1 [ Time Frame: 28 days ]
   Percentage of predicted (% pred) of the forced expiratory volume in 1 second (FEV1). FEV1 values that are ratios that are higher than at baseline suggest an improving health status. Assessment at Baseline and day 28 follow-up assessment
3. FEV1/FVC [ Time Frame: 28 days ]
   Ratio of percentage of predicted (% pred) of the forced expiratory volume in 1 second to (FEV1ercentage of predicted (% pred) of the forced vital capacity (FVC). FEV1/FVC ratios that are higher than at baseline suggest an improving health status. Assessment at baseline and day 28 follow-up assessment.
4. 6MWT [ Time Frame: 28 days ]
   The six-minute walk test (6MWT) is performed to capture the longest 6MWT for further analyses. The longer distance covered indicates an improving health status. Assessment at baseline and day 28 follow-up assessment.
5. COPD Exacerbations [ Time Frame: 90 days ]
   Exacerbations of chronic obstructive pulmonary disease (COPD) are episodes of worsening of symptoms, leading to substantial morbidity and mortality. Total number of exacerbations will be analyzed and measured at baseline, all follow-up and end of trial assessments. More exacerbations experienced over time indicate a worse health status.
6. Adverse Reactions [ Time Frame: 90 days ]
   The number of reported adverse reactions and serious adverse events per participant. The more adverse reactions, the worse the health status of the participant measured at baseline, all follow-up and end of trial assessments.

Other Outcome Measures:

1. CAT Score [ Time Frame: 90 days ]
   The COPD Assessment Test (CAT) is assessed to capture the health status. The total score ranges from 0 to 40 points. Change in CAT score measured at baseline, all follow-up and end of trial assessments between treatment and placebo arms with a higher scores indicating a more significant change in health status.
2. FEV1 [ Time Frame: 90 days ]
   Percentage of predicted (% pred) of the forced expiratory volume in 1 second (FEV1). Change in FEV1 measured at baseline, all follow-up and end of trial assessments between treatment and placebo arms with a higher scores indicating a more significant change in health status.
3. FEV1/FVC [ Time Frame: 90 days ]
   Ratio of percentage of predicted (% pred) of the forced expiratory volume in 1 second to (FEV1ercentage of predicted (% pred) of the forced vital capacity (FVC). FEV1/FVC measured at baseline, all follow-up and end of trial assessments between treatment and placebo arms with a higher scores indicating a more significant change in health status.
4. Vital Signs: Oxygen saturation [ Time Frame: 90 days ]
   Oxygen saturation (SpO2) measured at baseline, all follow-up and end of trial assessments between treatment and placebo arms with a higher scores indicating a more significant change in health status.
5. 6MWT [ Time Frame: 90 days ]
   The six-minute walk test (6MWT) is performed to capture the longest 6MWD for further analyses. 6MWT measured at baseline, all follow-up and end of trial assessments between treatment and placebo arms with a higher scores indicating a more significant change in health status.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. 18 years of age or older
2. History of moderate COPD as diagnosed by a physician
3. FEV1 /FVC Ratio < 0.7 with Post-Bronchodilator FEV1 ≥50% of predicted value at Screening
4. Modified Medical Research Council (mMRC) Dyspnea Scale score of Grade 2 or 3 (Appendix B) at Screening
5. CAT score of 12-20 (Appendix C) measured at Screening and confirmed at Baseline
6. Ability to consent
7. Ability to receive subcutaneous injections along the spine/back in the T-1 > T-5 region
8. Females of reproductive potential must have a negative pregnancy test at screening and use of highly effective contraception method (refer to section 12.3.9) for 4 weeks after study drug administration. Women are generally considered to be of reproductive potential if a non-menopausal female has not had a hysterectomy, bilateral oophorectomy, or medically documented ovarian failure.
9. Males of reproductive potential must use condoms with spermicide or other methods to ensure effective contraception with partner for 4 weeks after study drug administration. Men are generally considered to be of reproductive potential if they can produce sperm.

Exclusion Criteria:

1. Any medical condition that may put the participant at increased risk with exposure to botulinum toxin type A (BTX-A), including, but not limited to diagnoses of myasthenia gravis (MG), Eaton-Lambert syndrome, amyotrophic lateral sclerosis, multiple sclerosis, or any other significant disease that might interfere with neuromuscular function
2. Treatment of study target treatment area using acupuncture, transcutaneous electrical stimulation (TENS), cranial traction or injection of anesthetics/steroids within 4 weeks prior to the screening visit (oral or inhaled steroids are allowed)
3. Known allergy to BTX-A
4. Known history of pulmonary hypertension
5. Documented COPD exacerbation within 4 weeks of Baseline (Day 1)
6. Post-bronchodilator FEV1 value ≤30% of the predicted value at screening
7. Current smoker (e-cigarettes or cigarettes, cigars, pipe tobacco, vape)
8. Prior or current lung cancer
9. Post COVID symptoms resulting in breathing difficulties beyond pre-COVID COPD symptoms
10. Allergy to local anesthetics
11. History of botulism
12. Has an active pulmonary infection requiring systemic therapy within 14 days prior to the baseline visit
13. Known/documented medical history of clotting disorders
14. Pregnant or breastfeeding
15. Requires immediate admission to the hospital during screening that would render the participant unable to comply with the protocol
16. Any serious medical condition, such as kidney, liver, or cardiac disease, asthma, angioedema, bleeding disorder, malignancy, seizure, neutropenia, AIDS, that in the judgement of the Investigator could confound study assessments
17. Any condition (physical, mental, or social), occupational reason or other responsibility that, in the judgment of the Investigator, would jeopardize the safety or rights of the study participant, or render the participant unable to comply with the protocol, including participant's return for follow-up visits on schedule
18. Any chronic conditions which may cause diffusion of excess of Substance P in the cerebrospinal fluid (CSF), including but not limited to diabetes, chronic kidney failure, cirrhosis, pancreatitis, osteoporosis, ongoing clinical depression, migraines and fibromyalgia, that would compromise the participant's safety as determined by the Investigator.
19. History of keloid formation after injury.
20. Treatment with another investigational drug or other investigational intervention within 2 weeks of study start and throughout study duration
21. Treatment with any botulinum toxin (BoNT) products within 6 months of the baseline visit.
22. Any abnormal laboratory value greater than 3 times upper limit of normal (ULN) for albumin, total protein, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and bilirubin), and 5 times the upper limit of normal (ULN) for all other lab values.

Contacts and Locations

Locations

United States, Texas

Tranquil Clinical Research

Webster, Texas, United States, 77598

Sponsors and Collaborators

RMW Testing

Investigators

• Principal Investigator: Victoria Do; Investigator

More Information

• Responsible Party: RMW Testing
• ClinicalTrials.gov Identifier: NCT06003049
• Other Study ID Numbers: COPD 101
• First Posted: August 21, 2023
• Last Update Posted: May 10, 2024
• Last Verified: January 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Botulinum Toxins, Type A; abobotulinumtoxinA; Neuromuscular Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Acetylcholine Release Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Neurotransmitter Agents