Phase II Clinical Trial of Clenbuterol in Adult Patients With Pompe Disease

Phase II Clinical Trial of Clenbuterol in Adult Patients With Pompe Disease Stably Treated With Enzyme Replacement Therapy

The goals of this study are to determine safety and efficacy with regard to motor function of oral clenbuterol in combination with ERT in subjects with LOPD

Study Overview

• Status: Withdrawn
• Conditions: Pompe Disease (Late-onset)
• Intervention / Treatment: Drug: Clenbuterol; Drug: Placebos

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Diagnosis of Pompe disease by blood Acid alpha-glucosidase (GAA) assay and GAA gene sequencing,
2. Age: 18+ years at enrollment,
3. Receiving enzyme replacement therapy (ERT) at a stable dose for >104 weeks,
4. FVC >15% of expected (supine).
5. Subjects are capable of giving written consent.
6. Able to walk at least 100 meters on the 6 minute walk test (6MWT) (with assistive devices permitted).

Exclusion Criteria:

1. Continuous invasive ventilation (via tracheostomy or endotracheal tube)
2. 6MWT distance >90% of expected performance (% expected)
3. FVC >90% of expected (upright).
4. Clinically relevant illness within two weeks of enrollment including fever > 38.2o C, vomiting more than once in 24 hours, seizure, or other symptom deemed contraindicative to new therapy.
5. Chronic heart disease (Myocardial infarction, arrythmia, cardiomyopathy)
6. Tachycardia
7. History of seizure disorder
8. Hyperthyroidism
9. Pheochromocytoma
10. Pregnancy
11. History of diabetes
12. History of hypersensitivity to β2-agonist drugs such as albuterol, levalbuterol (Xopenex), bitolterol (Tornalate), pirbuterol (Maxair), terbutaline, salmeterol (Serevent),
13. Patients on a non-standard schedule for ERT; for example, weekly infusions as opposed to infusions every two weeks.
14. Treatment for asthma in the previous 12 months.
15. Renal insufficiency (elevated serum creatinine).
16. Having started respiratory muscle strength training in the last 6 months prior to study day 1 or having discontinued respiratory muscle strength training in the 6-month period preceding study day 1, or having started respiratory strength training greater than 6 months prior to study day 1 and unwilling to continue for the first year of study participation.
17. Received an investigational drug or participated in another interventional study within 90 days of Study Day 1.
18. Anti-rhGAA IgG with sustained titer >1:25.600 for >6 months at time of enrollment.

19. The use of the following concommitant meds is prohibited during the study:

    • diuretics (water pill);
    • digoxin (digitalis, Lanoxin);
    • beta-blockers such as atenolol (Tenormin), metoprolol (Lopressor), and propranolol (Inderal);
    • tricyclic antidepressants such as amitriptyline (Elavil, Etrafon), doxepin (Sinequan), imipramine (Janimine, Tofranil), and nortriptyline (Pamelor);
    • Monoamine oxidase (MAO) inhibitors such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate); or
    • other bronchodilators such as albuterol, levalbuterol (Xopenex), bitolterol (Tornalate), pirbuterol (Maxair), terbutaline (Brethine, Bricanyl), salmeterol (Serevent), isoetherine (Bronkometer), metaproterenol (Alupent, Metaprel), or isoproterenol (Isuprel Mistometer).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: clenbuterol; The initial dose of clenbuterol will be 40 mcg per oral each morning for one week, followed by 40 mcg twice per day (BID) for the next 5 weeks until Week 6. If the 40 mcg BID per oral is well tolerated, the dose will be increased to 80 mcg each morning/40 mcg each evening for one week, followed by 80 mcg BID for the next 5 weeks until the Week 12 visit. If 80 mcg BID is tolerated at Week 12, the subject will continue on that dose until Week 52.	Drug: Clenbuterol; 20 mcg spiropent tablets will be overencapsulated (two 20 mcg tablets per capsule); Other Names: Spiropent
Placebo Comparator: placebo; Initially, one capsule each morning for one week, followed by one capsule BID for the next 5 weeks until Week 6. If tolerated, the dose will be increased to two capsules each morning and 1 capsule each evening for one week, followed by two capsules BID for the next 5 weeks until the Week 12 visit. If two capsules BID is tolerated at Week 12, the subject will continue on that dose until Week 52.	Drug: Placebos; dextrose-filled capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Changes in 6 minute walk test (MWT) distance	Baseline (week 0) through 52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in pulmonary function tests: forced expiratory volume in 1 second (FEV1)		Baseline (week 0) through 52 weeks
Changes in pulmonary function tests: forced vital capacity (FVC)		Baseline (week 0) through 52 weeks
Changes in pulmonary function tests: maximum expiratory pressure (MEP)		Baseline (week 0) through 52 weeks
Changes in pulmonary function tests: Maximum inspiratory pressure (MIP)		Baseline (week 0) through 52 weeks
Changes in graded functional test: Gait, Stairs, Gower, Chair (GSCS)		Baseline (week 0) through 52 weeks
Changes in graded functional test: Quick Motor Function Test (QMFT)		Baseline (week 0) through 52 weeks
Changes in the concentration of alanine transaminase (ALT) in serum	Avoidance of liver toxicity as defined by a a persistent (sustained >2 weeks) >3x increase in aspartate aminotransferase (AST) or alanine aminotransferase (ALT) from the respective baseline values and/or an increase in direct, indirect or total bilirubin of >3x the upper limit of normal (no liver toxicity has been reported in association with clenbuterol administration and therefore repeat testing should be acceptable)	Baseline (week 0) through 52 weeks
Changes in the concentration of creatine kinase (CK) in serum	Avoidance of Worsening muscle involvement (i.e. muscle weakness, cramping, or fatigue) accompanied by a persistent (sustained >2 weeks) >3x increase in CK from baseline that is >2x the upper limit of normal (elevated CK is associated with LOPD and minor elevations of CK have been reported in association with clenbuterol administration, therefore repeat testing should be acceptable).	Baseline (week 0) through 52 weeks
Changes in the concentration of urinary glucose tetramer (Glc4)		Baseline (week 0) through 52 weeks

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Dwight Koeberl, MD, PhD, Duke University

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2023
• Primary Completion (Anticipated): June 30, 2025
• Study Completion (Anticipated): December 30, 2025

Study Registration Dates

• First Submitted: September 17, 2019
• First Submitted That Met QC Criteria: September 17, 2019
• First Posted (Actual): September 19, 2019

Study Record Updates

• Last Update Posted (Actual): August 17, 2022
• Last Update Submitted That Met QC Criteria: August 15, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: LOPD; Pompe disease; Late-onset Pompe Disease
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Lysosomal Storage Diseases, Nervous System; Glycogen Storage Disease; Glycogen Storage Disease Type II; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-Agonists; Sympathomimetics; Clenbuterol
• Other Study ID Numbers: Pro00102462

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
• product manufactured in and exported from the U.S.: No