Clinical trial NCT03000348: A Study of the Dosing, Efficacy, and Safety of Oral Cysteamine in Adult Patients With Cystic Fibrosis Exacerbations
Official title: A Randomized, Double-Blind, Parallel Group, Placebo-Controlled Study Investigating the Optimal Dose Regimen, Efficacy, and Safety of Adding Oral Cysteamine in Adult Patients Being Treated for an Exacerbation of CF-associated Lung Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cystic Fibrosis
Keywords: Exacerbation
CF
Lung disease
Lung infection
Gram negative
Bacterial Infection
pneumonia
bronchitis
Lead sponsor: NovaBiotics Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Agility Clinical, Inc.
name: PSR Group B.V.
First posted: 2016-12-22
Enrollment: 91
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: This is a multicenter, double-blind, randomized, placebo-controlled, 6-arm study to investigate the optimal dose regimen, efficacy, and safety of cysteamine in the treatment of adult patients with CF who are experiencing an exacerbation of CF-associated lung disease. Patients will be screened for the study and eligible patients will be randomized to receive either cysteamine or placebo as add-on therapy to their standard of care treatment for CF-associated lung disease.

Eligibility criteria: Inclusion Criteria:

1. CF-associated lung disease with documented history of chronic infection with Gram-negative organism(s)
2. Established patient of the Principal Investigator's CF Multi Disciplinary Team (MDT)
3. Age ≥18 years
4. Weight \>40 kg
5. FEV1 \>30% of predicted within the 6 months prior to study exacerbation
6. 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
7. 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:

   1. intrauterine device (IUD);
   2. surgical sterilization of the partner (vasectomy for 6 months minimum);
   3. combined (estrogen or progestogen containing) hormonal contraception associated with the inhibition of ovulation (either oral, intravaginal, or transdermal);
   4. progestogen only hormonal contraception associated with the inhibition of ovulation (either oral, injectable, or implantable);
   5. intrauterine hormone releasing system (IUS);
   6. bilateral tubal occlusion.
8. 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.
9. 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:

   1. hysteroscopic sterilization;
   2. bilateral tubal ligation or bilateral salpingectomy;
   3. hysterectomy;
   4. bilateral oophorectomy; or be postmenopausal with amenorrhea for at least 1 year prior to the first study drug dose and follicle stimulating hormone (FSH) serum levels consistent with postmenopausal status.
10. A non-vasectomized male subject agrees to use a condom with spermicide or abstain from sexual intercourse during the study until 90 days beyond the last dose of study medication and the female partner agrees to comply with inclusion 7 or 9. For a vasectomized male who has had his vasectomy 6 months or more prior to study start, it is required that they use a condom during sexual intercourse. A male who has been vasectomized less than 6 months prior to study start must follow the same restrictions as a non-vasectomized male.
11. If male, agrees not to donate sperm from the first study drug dose until 90 days after dosing.
12. Willing and able to comply with all protocol requirements and procedures, including induction of sputum, if necessary
13. Willing and able to provide signed and dated informed consent

Exclusion Criteria:

1. Hypersensitive to cysteamine or to any of the excipients
2. Hypersensitive to penicillamine
3. Transplant recipient
4. Participation in any other interventional clinical research study (participation in observational studies is not exclusionary) within 30 days of Baseline (Day 0), and any planned participation in an interventional clinical research study for the duration of this study
5. If female, pregnancy, planned pregnancy, or breast-feeding
6. 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

Primary outcomes:
measure: Change From Baseline in Sputum Bacterial Load
timeFrame: Baseline through Day 21/End of Study
measure: Safety and Tolerability Assessed by the Number of Subjects With Adverse Events
timeFrame: Baseline through Day 21/End of Study
Secondary outcomes:
measure: Change From Baseline in Neutrophil Elastase Levels
timeFrame: Baseline through Day 21/End of Study
measure: Change From Baseline in Sputum IL8
timeFrame: Baseline through Day 21/End of Study
measure: Change From Baseline in FEV1
timeFrame: Baseline through Day 21/End of Study
measure: Change From Baseline in BMI
timeFrame: Baseline through Day 21/End of Study
measure: Change From Baseline in C-Reactive Protein
timeFrame: Baseline through Day 21
measure: Change From Baseline in Blood Leukocyte Count
timeFrame: Baseline through Day 21/End of Study
measure: Assessment of Blood Cysteamine Levels
timeFrame: Day 14
measure: Assessment of Sputum Cysteamine Levels
timeFrame: Day 14
measure: Change From Baseline in CFRSD-CRISS
timeFrame: Baseline through to Day 21
measure: Change From Baseline in CFQ-R
timeFrame: Baseline through Day 21/End of Study
measure: Change From Baseline in Jarad and Sequeiros Symptom Score Questionnaire
timeFrame: changes from baseline at day 7 and day 14
measure: Change From Baseline in Weight
timeFrame: Baseline through Day 21/End of Study
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Banner University of Arizona Medical Center
state: Arizona
city: San Francisco
country: United States
facility: San Francisco Critical Care Medical Group California Pacific Medical Center
state: California
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Orlando
country: United States
facility: Central Florida Pulmonary
state: Florida
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
city: Milwaukee
country: United States
facility: The Medical College of Wisconsin/Froedtert Hospital
state: Wisconsin
city: Roma
country: Italy
facility: Ospedale Padiatrico Bambino Gesu Centro Fibrosi Cistica
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrato di Verona Borgo Trento Centro Fibrosi Cistica
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
state: Scotland
city: Dundee
country: United Kingdom
facility: Ninewells Hospital Scottish Adult Cystic Fibrosis Service
city: Edinburgh
country: United Kingdom
facility: Western General Hospital Edinburgh, CF Adults / CF Unit
city: Glasgow
country: United Kingdom
facility: NHS GGC
city: Inverness
country: United Kingdom
facility: Raigmore Hospital
city: Leeds
country: United Kingdom
facility: St. James University Hospital
city: Newcastle upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary Adult CF Centre
Study officials:
References:
citation: 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.