A Phase II, Dose Ranging, Multicenter, Double-blind, Placebo Controlled Study to Evaluate Safety and Effects of (R)-Roscovitine in Adults Subjects With Cystic Fibrosis, Carrying 2 Cystic Fibrosis Causing Mutations With at Least One F508del-CFTR Mutation and Chronically Infected With Pseudomonas Aeruginosa, a Study Involving 36 CF Patients (24 Treated, 12 Controls). ROSCO-CF.
Overview
- Phase
- Phase 2
- Intervention
- Roscovitine
- Conditions
- Cystic Fibrosis
- Sponsor
- University Hospital, Brest
- Enrollment
- 49
- Locations
- 11
- Primary Endpoint
- Safety of increasing doses of Roscovitine
- Status
- Terminated
- Last Updated
- 4 months ago
Overview
Brief Summary
This is a phase II, dose ranging, multicenter, randomized, double-blind, placebo-controlled study.
The aim of this study is to assess the safety of increasing doses of roscovitine administered orally for 4 cycles of 4 consecutive days (treatment "on") separated by a 3 days treatment free period (treatment "off") in adult CF subjects with Cystic Fibrosis carrying 2 Cystic Fibrosis causing mutations with at least one F508del-CFTR mutation and chronically infected with Pseudomonas aeruginosa.
This study involved 36 Cystic Fibrosis patients: 24 treated and 12 controls.
Detailed Description
ROSCO-CF is a phase II, dose ranging, multicenter, double-blind, placebo controlled study to evaluate safety and effects of (R)-roscovitine in subjects with Cystic Fibrosis carrying 2 Cystic Fibrosis causing mutations with at least one F508del-CFTR mutation and chronically infected with Pseudomonas aeruginosa. The aim of this study is to assess the safety of increasing doses of roscovitine administered orally for 4 cycles of 4 consecutive days (treatment "on") separated by a 3 days treatment free period (treatment "off") in 36 adult cystic fibrosis subjects. These 36 patients will be allocated to 3 groups of 12 subjects who will be randomized in a 2:1 ratio (active drug to matching placebo). In each group, 8 patients will receive roscovitine (200 mg, 400 mg, 2 X 400 mg in group 1, 2 and 3, respectively) and 4 will receive a matching placebo. Treatment will be provided by oral administration of capsules. Each patient will receive the same treatment throughout the 28 day study. This phase II trial will give some preliminary information about safety and hints of effects of a new experimental treatment. If the data suggest that a short term treatment with roscovitine provides a safe, effective and convenient approach for CF patients chronically infected with Pseudomonas aeruginosa, patients participating in this proof of concept trial will be offered to participate in further longer term studies.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female aged over 18 years of age on the date of informed consent;
- •Diagnosed CF patients. Confirmed diagnosis of CF (Rosenstein and Cutting, 1998);
- •Patients carrying 2 Cystic Fibrosis causing mutations with at least one F508del-CFTR mutation, genotype to be confirmed at screening;
- •Forced expiratory volume at 1 second (FEV1) 40%
- •Chronic lung Pseudomonas aeruginosa infection according to the definition from the French Consensus Conference;
- •Able to understand and comply with all protocol requirements, restrictions and instructions and likely to complete the study as planned (as judged by the investigator);
- •Provide written informed consent prior to the performance of any study-related procedure;
Exclusion Criteria
- •Acute upper or lower respiratory infection, pulmonary exacerbation or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before V2;
- •Recent patient reported history of:
- •non recovered viral upper respiratory tract infection
- •solid organ or hematological transplantation
- •Burkholderia cepacia complex or Non Tuberculous Mycobacteria (NTM) respiratory tract infection;
- •Undergone major surgery within 1 month prior to screening;
- •Currently treated allergic broncho-pulmonary aspergillosis (ABPA);
- •Diabetic patients whose blood glucose is poorly controlled as evidenced by HbA1C \>8%;
- •Hemoptysis more than 60 mL at any time within 4 weeks prior to first study drug administration (V2);
- •History of any other comorbidity that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject;
Arms & Interventions
Group 2
400 mg roscovitine (8) or placebo (4) once daily for 4 cycles of 7 days (4 days "on" and 3 days "off")
Intervention: Roscovitine
Group 1
200 mg roscovitine (8) or placebo (4) once daily for 4 cycles of 7 days (4 days "on" and 3 days "off")
Intervention: Roscovitine
Group 1
200 mg roscovitine (8) or placebo (4) once daily for 4 cycles of 7 days (4 days "on" and 3 days "off")
Intervention: Placebo
Group 2
400 mg roscovitine (8) or placebo (4) once daily for 4 cycles of 7 days (4 days "on" and 3 days "off")
Intervention: Placebo
Group 3
400 mg roscovitine (8) or (4) placebo twice daily for cycles of 7 days (4 days "on" and 3 days "off")
Intervention: Roscovitine
Group 3
400 mg roscovitine (8) or (4) placebo twice daily for cycles of 7 days (4 days "on" and 3 days "off")
Intervention: Placebo
Outcomes
Primary Outcomes
Safety of increasing doses of Roscovitine
Time Frame: 3 months
The primary objective of this study is to assess the safety of increasing doses of roscovitine administered orally for 4 cycles of 4 consecutive days (treatment "on") separated by a 3 days treatment free period (treatment "off") in adult CF subjects who carrying 2 Cystic Fibrosis causing mutations with at least F508del mutation
Secondary Outcomes
- C-reactive protein(3 months)
- Forced expiratory volume in 1 second(3 months)
- Change in the concentration of Pseudomonas Aeruginosa(3 months)
- Cystic Fibrosis Questionnaire-Revised(3 months)
- Sweat Chloride Concentration(3 months)
- Nasal Potential Difference(3 months)
- Pain questionnaire(3 months)
- Pro- and anti-inflammatory cytokines(3 months)
- Body Mass Index(3 months)
- PK parameters(3 months)