A Study of the Dosing, Efficacy, and Safety of Oral Cysteamine in Adult Patients With Cystic Fibrosis Exacerbations

NCT03000348 | Completed Phase 2 Results DMC

• 1 other identifier: NBTCS02
• Study Type: interventional
• Target: 91
• Locations: 3 countries
• Sites: 17

Brief Summary

This study investigates the use of cysteamine in the treatment of adults with Cystic Fibrosis who are experiencing an exacerbation of CF-associated lung disease. There are six different potential dosing regimens, including one that is placebo.

Conditions

Cystic Fibrosis

Keywords

Exacerbation; CF; Lung disease; Lung infection; Gram negative; Bacterial Infection; pneumonia; bronchitis

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in Sputum Bacterial Load

  Change from baseline through to Day 21 in log10 cfu/ml transformed total gram negative sputum bacterial load

  Baseline through Day 21/End of Study

• Safety and Tolerability Assessed by the Number of Subjects With Adverse Events

  Assessed by variables such as adverse events (AEs), laboratory assessments, physical examinations, and vital signs.

  Baseline through Day 21/End of Study

Secondary Outcomes (12)

• Change From Baseline in Neutrophil Elastase Levels

  Baseline through Day 21/End of Study

• Change From Baseline in Sputum IL8

  Baseline through Day 21/End of Study

• Change From Baseline in FEV1

  Baseline through Day 21/End of Study

• Change From Baseline in BMI

  Baseline through Day 21/End of Study

• Change From Baseline in C-Reactive Protein

  Baseline through Day 21

Study Arms (6)

High Dose, Once per day

ACTIVE COMPARATOR

Patient takes one oral dose of Cysteamine (high dose) per day, in the morning. The patient takes two oral placebo doses, one at mid-day and one in the evening.

Drug: Cysteamine; Drug: Placebo Oral Capsule

High Dose, Twice per day

ACTIVE COMPARATOR

Patient takes two oral doses of Cysteamine (high dose) per day, one in the morning and one in the evening. The patient takes one oral placebo dose, at mid-day.

Drug: Cysteamine; Drug: Placebo Oral Capsule

High Dose, Three times per day

ACTIVE COMPARATOR

Patient takes three oral doses of Cysteamine (high dose) per day, one in the morning, one at mid-day and one in the evening.

Drug: Cysteamine

Placebo

PLACEBO COMPARATOR

Patient takes three oral doses of placebo, one in the morning, one at mid-day and one in the evening.

Drug: Placebo Oral Capsule

Low Dose, Three times per day

ACTIVE COMPARATOR

Patient takes three oral doses of Cysteamine (low dose) per day, one in the morning, one at mid-day and one in the evening.

Drug: Cysteamine; Drug: Placebo Oral Capsule

Mid-Range Dose, Three times per day

ACTIVE COMPARATOR

Patient takes three oral doses of Cysteamine (mid-range dose) per day, one in the morning, one at mid-day and one in the evening.

Drug: Cysteamine; Drug: Placebo Oral Capsule

Interventions

Cysteamine DRUG

Oral Cysteamine Capsule

Also known as: Lynovex, NM001, Lynovex Oral

High Dose, Once per day; High Dose, Three times per day; High Dose, Twice per day; Low Dose, Three times per day; Mid-Range Dose, Three times per day

Placebo Oral Capsule DRUG

Placebo Oral Capsule

High Dose, Once per day; High Dose, Twice per day; Low Dose, Three times per day; Mid-Range Dose, Three times per day; Placebo

Eligibility Criteria

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

You may qualify if:

• CF-associated lung disease with documented history of chronic infection with Gram-negative organism(s)
• Established patient of the Principal Investigator's CF Multi Disciplinary Team (MDT)
• Age ≥18 years
• Weight \>40 kg
• FEV1 \>30% of predicted within the 6 months prior to study exacerbation
• At the baseline visit: experiencing a new exacerbation of CF-associated lung disease (based on Investigator assessment of ≥4 symptoms present on the Fuchs' criteria) requiring treatment that includes an aminoglycoside antibiotic
• Females of childbearing potential will be included if they are either sexually inactive (sexually abstinent for 14 days prior to the first study drug dose continuing through 28 days after the last study drug dose, or using one of the following highly effective contraceptive (i.e. results in \<1% failure rate when used consistently and correctly) methods in this trial:
• intrauterine device (IUD);
• surgical sterilization of the partner (vasectomy for 6 months minimum);
• combined (estrogen or progestogen containing) hormonal contraception associated with the inhibition of ovulation (either oral, intravaginal, or transdermal);
• progestogen only hormonal contraception associated with the inhibition of ovulation (either oral, injectable, or implantable);
• intrauterine hormone releasing system (IUS);
• bilateral tubal occlusion.
• Females of childbearing potential agree to remain sexually inactive or to keep the same birth control method for at least 28 days following the last dose.
• A female of non-childbearing potential must have undergone one of the following sterilization procedures at least 6 months prior to the first study drug dose:

You may not qualify if:

• Hypersensitive to cysteamine or to any of the excipients
• Hypersensitive to penicillamine
• Transplant recipient
• If female, pregnancy, planned pregnancy, or breast-feeding
• Any other significant disease/disorder which, in the Investigator's opinion, either puts the patient at risk due to study participation, or may influence the results of the study or the patient's ability to participate in the study

Sponsors & Collaborators

• NovaBiotics Ltd.: lead
• Agility Clinical, Inc.: collaborator
• PSR Group B.V.: collaborator

Study Sites (17)

Banner University of Arizona Medical Center

Tucson, Arizona, 85724, United States

Location

San Francisco Critical Care Medical Group California Pacific Medical Center

San Francisco, California, 94115, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Central Florida Pulmonary

Orlando, Florida, 32803, United States

Location

Albany Medical College

Albany, New York, 12208, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

West Virginia University

Morgantown, West Virginia, 26506, United States

Location

The Medical College of Wisconsin/Froedtert Hospital

Milwaukee, Wisconsin, 53226, United States

Location

Ospedale Padiatrico Bambino Gesu Centro Fibrosi Cistica

Roma, 00165, Italy

Location

Azienda Ospedaliera Universitaria Integrato di Verona Borgo Trento Centro Fibrosi Cistica

Verona, 37126, Italy

Location

Aberdeen Royal Infirmary

Aberdeen, Scotland, AB25 2ZN, United Kingdom

Location

Ninewells Hospital Scottish Adult Cystic Fibrosis Service

Dundee, DD1 9SY, United Kingdom

Location

Western General Hospital Edinburgh, CF Adults / CF Unit

Edinburgh, EH4 3HE, United Kingdom

Location

NHS GGC

Glasgow, G51 4TF, United Kingdom

Location

Raigmore Hospital

Inverness, IV2 3UJ, United Kingdom

Location

St. James University Hospital

Leeds, LS9 7TF, United Kingdom

Location

Royal Victoria Infirmary Adult CF Centre

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

Related Publications (1)

• Devereux G, Wrolstad D, Bourke SJ, Daines CL, Doe S, Dougherty R, Franco R, Innes A, Kopp BT, Lascano J, Layish D, MacGregor G, Murray L, Peckham D, Lucidi V, Lovie E, Robertson J, Fraser-Pitt DJ, O'Neil DA. Oral cysteamine as an adjunct treatment in cystic fibrosis pulmonary exacerbations: An exploratory randomized clinical trial. PLoS One. 2020 Dec 28;15(12):e0242945. doi: 10.1371/journal.pone.0242945. eCollection 2020.

  PMID: 33370348 DERIVED

Related Links

• NovaBiotics Website

MeSH Terms

Conditions

Cystic Fibrosis; Lung Diseases; Bacterial Infections; Pneumonia; Bronchitis

Interventions

Cysteamine

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Bronchial Diseases; Lung Diseases, Obstructive

Intervention Hierarchy (Ancestors)

Mercaptoethylamines; Ethylamines; Amines; Organic Chemicals; Sulfhydryl Compounds; Sulfur Compounds

Results Point of Contact

• Title: Dr Deborah O'Neil, CEO
• Organization: NovaBiotics Ltd

deborah@novabiotics.co.uk

01224 711 377

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2016
• First Posted: December 22, 2016
• Study Start: December 1, 2016
• Primary Completion: April 1, 2018
• Study Completion: April 1, 2018
• Last Updated: April 14, 2021
• Results First Posted: April 14, 2021

Record last verified: 2021-04

Locations

US (8); IT (2); GB (7)