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

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)

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.

Study Overview

• Status: Completed
• Conditions: COPD
• Intervention / Treatment: Drug: OnabotulinumtoxinA; Other: Placebo

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 Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Webster, Texas, United States, 77598
      • Tranquil Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Treatment Arm; OnabotulinumtoxinA	Drug: OnabotulinumtoxinA; BOTOX injection series; Other Names: BOTOX
Placebo Comparator: Placebo Arm; Normal saline	Other: Placebo; Placebo injection series

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CAT (Average)	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.	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CAT (Change in Units)	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.	28 days
FEV1	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	28 days
FEV1/FVC	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.	28 days
6MWT	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.	28 days
COPD Exacerbations	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.	90 days
Adverse Reactions	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.	90 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
CAT Score	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.	90 days
FEV1	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.	90 days
FEV1/FVC	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.	90 days
Vital Signs: Oxygen saturation	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.	90 days
6MWT	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.	90 days

Collaborators and Investigators

• Sponsor: RMW Testing
• Investigators: Principal Investigator: Victoria Do, Investigator

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2023
• Primary Completion (Actual): April 24, 2024
• Study Completion (Actual): July 10, 2024

Study Registration Dates

• First Submitted: August 4, 2023
• First Submitted That Met QC Criteria: August 17, 2023
• First Posted (Actual): August 21, 2023

Study Record Updates

• Last Update Posted (Actual): July 17, 2024
• Last Update Submitted That Met QC Criteria: July 15, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Botulinum Toxins, Type A; abobotulinumtoxinA
• Other Study ID Numbers: COPD 101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No