Safety and Efficacy of Clenbuterol in Individuals With Late-onset Pompe Disease and Receiving Enzyme Replacement Therapy

NCT01942590 | Completed Phase 1 Results DMC

• 2 other identifiers: Pro00043680R01FD004364
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

Funding Source- FDA OOPD The purpose of this study is to investigate the safety and efficacy of clenbuterol on motor function in individuals with late-onset Pompe disease (LOPD) who are treated with enzyme replacement therapy (ERT).

Conditions

Pompe Disease

Keywords

Pompe disease

Outcome Measures

Primary Outcomes (2)

• Number of Participants With a Change in Creatine Kinase (CK) Reflecting Worsening of Muscle Involvement

  Worsening muscle involvement, as defined by \>3x increase in CK from baseline that is \>2x the upper limit of normal

  Any point up to week 52

• Number of Participants With a Change in Aspartate Aminotransferase (AST), Alanine Transaminase (ALT), and Bilirubin Representing Liver Toxicity

  Liver toxicity, as defined by a \>3x increase in AST or ALT from the respective baseline values and/or an increase in direct, indirect or total bilirubin of \>3x the upper limit of normal

  Any point up to week 52

Secondary Outcomes (11)

• Change in 6 Minute Walk Test

  Baseline, week 18

• Change in 6 Minute Walk Test

  Baseline, week 52

• Change in Forced Vital Capacity (FVC) in Pulmonary Function Testing

  Baseline, Week 18

• Change in Forced Vital Capacity (FVC) in Pulmonary Function Testing

  Baseline, Week 52

• Change in Urinary Glc4 Biomarker

  Baseline, Week 18

Study Arms (2)

Clenbuterol

EXPERIMENTAL

Initially, 40 mcg each morning for one week. Then, increase to 40 mcg BID for the next 5 weeks. If tolerated, will increase to 80 mcg in the morning and 40 mcg in the evening for one week. Then, last dose increase will be 80 mcg BID until week 52.

Drug: Clenbuterol

Placebo Comparator

PLACEBO COMPARATOR

Initially, one capsule each morning for one week. Then, increase to one capsule BID for the next 5 weeks. If tolerated, will increase to two capsules in the morning and one capsule in the evening for one week. Then, last dose increase will be two capsules BID until week 52.

Drug: Placebo

Interventions

Clenbuterol DRUG

Also known as: Spiropent

Clenbuterol

Placebo DRUG

Also known as: Capsule

Placebo Comparator

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of Pompe disease by blood acid alpha-glucosidase assay and acid alpha-glucosidase gene sequencing,
• Age: 18+ years at enrollment,
• Receiving ERT at standard dose (20 mg/kg every 2 weeks) for at least 52 weeks,
• Subjects are capable of giving written consent.

You may not qualify if:

• Continuous invasive ventilation (via tracheostomy or endotracheal tube)
• Clinically relevant illness within two weeks of enrollment including fever \> 38.2 C, vomiting more than once in 24 hours, seizure, or other symptom deemed contraindicative to new therapy.
• Chronic heart disease (Myocardial infarction, arrythmia, cardiomyopathy)
• Tachycardia
• History of seizure disorder
• Hyperthyroidism
• Pheochromocytoma
• Pregnancy
• History of diabetes
• History of hypersensitivity to beta 2-agonist drugs such as albuterol, levalbuterol (Xopenex), bitolterol (Tornalate), pirbuterol (Maxair), terbutaline, salmeterol (Serevent),
• Patients on a non-standard schedule for ERT; for example, weekly infusions as opposed to infusions every two weeks.
• Treatment for asthma in the previous 12 months.
• The use of the following concommitant meds is prohibited during the study:
• diuretics (water pill);
• digoxin (digitalis, Lanoxin);

Sponsors & Collaborators

• Dwight Koeberl, M.D., Ph.D.: lead

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Publications (4)

• Kamalakkannan G, Petrilli CM, George I, LaManca J, McLaughlin BT, Shane E, Mancini DM, Maybaum S. Clenbuterol increases lean muscle mass but not endurance in patients with chronic heart failure. J Heart Lung Transplant. 2008 Apr;27(4):457-61. doi: 10.1016/j.healun.2008.01.013.

  PMID: 18374884 BACKGROUND

• Koeberl DD, Luo X, Sun B, McVie-Wylie A, Dai J, Li S, Banugaria SG, Chen YT, Bali DS. Enhanced efficacy of enzyme replacement therapy in Pompe disease through mannose-6-phosphate receptor expression in skeletal muscle. Mol Genet Metab. 2011 Jun;103(2):107-12. doi: 10.1016/j.ymgme.2011.02.006. Epub 2011 Feb 13.

  PMID: 21397538 BACKGROUND

• Koeberl DD, Li S, Dai J, Thurberg BL, Bali D, Kishnani PS. beta2 Agonists enhance the efficacy of simultaneous enzyme replacement therapy in murine Pompe disease. Mol Genet Metab. 2012 Feb;105(2):221-7. doi: 10.1016/j.ymgme.2011.11.005. Epub 2011 Nov 11.

  PMID: 22154081 BACKGROUND

• Koeberl DD, Case LE, Smith EC, Walters C, Han SO, Li Y, Chen W, Hornik CP, Huffman KM, Kraus WE, Thurberg BL, Corcoran DL, Bali D, Bursac N, Kishnani PS. Correction of Biochemical Abnormalities and Improved Muscle Function in a Phase I/II Clinical Trial of Clenbuterol in Pompe Disease. Mol Ther. 2018 Sep 5;26(9):2304-2314. doi: 10.1016/j.ymthe.2018.06.023. Epub 2018 Jul 5.

  PMID: 30025991 DERIVED

MeSH Terms

Conditions

Glycogen Storage Disease Type II

Interventions

Clenbuterol; Capsules

Condition Hierarchy (Ancestors)

Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Glycogen Storage Disease; Carbohydrate Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Dosage Forms; Pharmaceutical Preparations

Results Point of Contact

• Title: Dwight Koeberl, M.D., Ph.D.
• Organization: Duke University Health System

dwight.koeberl@duke.edu

919-684-2036

Study Officials

• Dwight D Koeberl, MD, PhD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: September 11, 2013
• First Posted: September 16, 2013
• Study Start: September 1, 2013
• Primary Completion: September 2, 2016
• Study Completion: September 2, 2016
• Last Updated: July 2, 2019
• Results First Posted: October 23, 2017

Record last verified: 2019-06

Locations

US (1)