Evaluation of (R)-Roscovitine Safety and Effects in Subjects With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02649751
• Date of registration: 06/01/2016
• Prospective Registration: Yes
• Primary sponsor: University Hospital, Brest
• Public title: Evaluation of (R)-Roscovitine Safety and Effects in Subjects With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation ROSCO-CF
• Scientific title: 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.
• Date of first enrolment: February 22, 2016
• Target sample size: 49
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT02649751
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 2

Countries of recruitment

France

Contacts

• Name: Gilles RAULT, MD
• Affiliation: Centre de Pérharidy - Roscoff

Key inclusion & exclusion 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;

- Any other clinically significant conditions (not associated with the study indication)
at Screening (V1) which might interfere with the assessment of this study;

- Any of the following abnormal laboratory values at screening:

- Hemoglobin <10 g/dL

- Abnormal liver function

- Serum K+ <3,5 mmol/L

- Abnormal renal function

- Any clinically significant laboratory abnormalities;

- Patients who have clinically significant impairment in cardiovascular function;

- Concomitant disease(s) that could prolong the QT interval;

- Patients with a history of alcohol or drug abuse in the past year;

- Patients with a history of noncompliance to medical regimens and patients or
caregivers who are considered potentially unreliable;

- Use of one (or several) prohibited medications and/or food;

- Administration of any investigational drug within 30 days prior to Screening (V1) or 5
half-lives, whichever is longer;

- Use of systemic anti-pseudomonal antibiotics within 28 days prior to first study drug
administration (V2). However use of inhaled anti-pseudomonal antibiotic treatment is
allowed if initiated for more than 28 days;

- Use of loop diuretics within 7 days prior to first study drug administration (V2);

- Pregnant or nursing females.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Cystic Fibrosis

Intervention(s)

Drug: Roscovitine

Drug: Placebo

Primary Outcome(s)

Safety of increasing doses of Roscovitine [Time Frame: 3 months]

Secondary Outcome(s)

Body Mass Index [Time Frame: 3 months]

PK parameters [Time Frame: 3 months]

C-reactive protein [Time Frame: 3 months]

Cystic Fibrosis Questionnaire-Revised [Time Frame: 3 months]

Nasal Potential Difference [Time Frame: 3 months]

Pro- and anti-inflammatory cytokines [Time Frame: 3 months]

Pain questionnaire [Time Frame: 3 months]

Change in the concentration of Pseudomonas Aeruginosa [Time Frame: 3 months]

Forced expiratory volume in 1 second [Time Frame: 3 months]

Sweat Chloride Concentration [Time Frame: 3 months]

Secondary ID(s)

RB 15.098 (ROSCO CF)

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

ManRos Therapeutics

Cyclacel Pharmaceuticals, Inc.