DeltaF508 Homozygous Cystic Fibrosis MedDRA version: 20.0 Level: PT Classification code 10011762 Term: Cystic fibrosis System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Trade Name: Cystagon
Product Name: Cystagon
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: cysteamine bitartrate
CAS Number: 27761-19-9
Other descriptive name: 2-aminoethanethiol
2,3-dihydroxybutanedioic acid
Sponsors
University of LIverpool
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Adult Inclusion Criteria 1. Patient managed by respiratory team at Leeds General Infirmary 2. Patient has homozygous ?F508 Cystic Fibrosis 3. 18-30 years old at screening visit 4. Written informed consent obtained from patient. This person must understand the contents of the consent, requirements of the study and have had an opportunity to review questions with a medically trained member of the site study team. 5. Patient must have a good understanding of the English language, in which the consent forms are available, and understand the requirements for reporting of any AE to the Investigator. 6. If female, be willing to have a pregnancy test and use one or more of the following methods of highly effective contraception: Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation Oral Intravaginal Transdermal Progestogen-only hormonal contraception associated with inhibition of ovulation Oral Injectable Implantable Intrauterine device (IUD) Intrauterine hormone-releasing system ( IUS) Bilateral tubal occlusion Vasectomised partner Sexual abstinence 7. Patient willing and able to comply with protocol including swallowing capsules and venepuncture/cannulation weekly for 6 weeks Paediatric Inclusion Criteria 8. Patient managed by respiratory team at Alder Hey Children’s NHS Foundation Trust 9. Patient has homozygous ?F508 Cystic Fibrosis 10. 5-17 years at screening visit 11. Written informed consent from parent/legal guardian if patient =65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: Adult Exclusion Criteria 1. Use of EGCG, or drinking green tea within 2 weeks of the first dose of study and during study period 2. Use of Ivacaftor, Lumacaftor or other mutations specific therapy 3. Drinking black tea within 2 weeks of the first dose of study drugs, and during the study period 4. Known hypersensitivity to Cysteamine, EGCG, or penicillamine 5. Known hypersensitivity to the excipients of the study drugs (i.e. microcrystalline cellulose, pregelatinized starch, magnesium stearate/sodium lauryl sulfate, colloidal silicon dioxide, croscarmellose sodium gelatin, titanium dioxide, black ink on hard capsules containing E172). 6. Recent infective exacerbation of CF. Patient must not have had oral antibiotics within 4 weeks of screening or IV antibiotics within 6 weeks of screening 7. Any clinically significant acute illness within 4 weeks of the start of dose administration. 8. Any clinically significant medical condition, other than CF that in the opinion of the Investigator may increase the risk of participating in the study or interfere with the interpretation of safety or efficacy evaluations (e.g., severe reflux, psychiatric condition or behavioural disorder). 9. Patient on regular itraconazole 10. Liver function tests deemed too abnormal by a clinician experienced in the management of cystic fibrosis. 11. Renal function abnormal for age. 12. Significantly low red cell folate level 13. Pregnant or breastfeeding 14. Written consent not obtained. 15. The patient is deemed unsuitable at the discretion of the investigator. 16. Patients unable to swallow tablets/capsule by mouth Paediatric Exclusion Criteria 1. Use of EGCG, or drinking green tea within 2 weeks of the first dose of study and during study period 2. Use of Ivacaftor, Lumacaftor or other mutations specific therapy 3. Drinking black tea within 2 weeks of the first dose of study drugs, and during the study period 4. Known hypersensitivity to cysteamine or EGCG 5. Known hypersensitivity to the excipients of the study drugs (i.e. microcrystalline cellulose, pregelatinized starch, magnesium stearate/sodium lauryl sulfate, colloidal silicon dioxide, croscarmellose sodium gelatin, titanium dioxide, black ink on hard capsules containing E172). 6. Recent infective exacerbation of CF. Patient must not have had oral antibiotics within 4 weeks of screening or IV antibiotics within 6 weeks of screening 7. Any clinically significant acute illness within 4 weeks of the start of dose administration. 8. Any clinically significant medical condition, other than CF that in the opinion of the Investigator may increase the risk of participating in the study or interfere with the interpretation of safety or efficacy evaluations (e.g., severe reflux, psychiatric condition or behavioural disorder). 9. Patient on regular itraconazole 10. Liver function tests deemed too abnormal by a clinician experienced in the management of cystic fibrosis. 11. Renal function abnormal for age. 12. Significantly low red cell folate level 13. Pregnant or breastfeeding 14. Written consent not obtained. 15. Participant who understands the study (judged on case by case basis, from approximately age 7) declines assent. 16. The patient is deemed unsuitable at the discretion of the investigator. 17. Patients unable to swallow tablets/capsule by mouth
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: In two cohorts of patients (adult and paediatric) with a particular genetic cause of cystic fibrosis (deltaF 508, the most common and one of the most severe types), can patients tolerate an existing medicine (cysteamine) while taking a food supplement (EGCG). The primary outcome measure is discontinuation of the cysteamine. There are well known adverse effects for cysteamine. We also want to capture the suspected ADRs from this medication.;Secondary Objective: For a subgroup of patients, we want to measure blood levels of cysteamine, to ensure we are dosing appropriately. In addition, in all the participants, we want to repeat the tests of effectiveness (sweat test), as they have only been done in a small population before, and not in children. ;Primary end point(s): 1. Discontinuation of the study drug 2. Adverse effects of cysteamine in homozygous ?508 cystic fibrosis adult and paediatric patients ;Timepoint(s) of evaluation of this end point: The study will last for 6 weeks. This comprises 4 weeks where the cysteamine dose is increased (as per usual dosing in cystinosis) while a single dose of EGCG is administered. On week 5, the participants remain on the dose of cysteamine, but a single dose increase in EGCG is undertaken. In the final week, no medications are used. Patients will have weekly review to ensure they are able to take the medications, and to assess for adverse effects of the medications. Safety bloods will also be undertaken weekly. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Plasma concentration of cysteamine and EGCG at set time points in ?F508 cystic fibrosis patients. 2. Change in sweat test chloride result with each dose escalation of cysteamine 3. Change in sweat test chloride result with cysteamine used in combination with multiple daily dose EGCG ;Timepoint(s) of evaluation of this end point: A subset of patients (10 per cohort) will have additional blood taken for PK analysis at their weekly reviews. All participants will have a weekly sweat test, as a means to replicate the reduction in sweat chloride seen in adult patients and establish if this occurs in paediatric patients. | — |
Countries
United Kingdom
Contacts
Public ContactDr Dan Hawcutt
University of Liverpool
Outcome results
None listed