ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02649751
Recruitment Status : Recruiting
First Posted : January 7, 2016
Last Update Posted : April 4, 2018
Sponsor:
Collaborators:
ManRos Therapeutics
Cyclacel Pharmaceuticals, Inc.
Information provided by (Responsible Party):
University Hospital, Brest

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.


Condition or disease Intervention/treatment Phase
Cystic Fibrosis Drug: Roscovitine Drug: Placebo Phase 2

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official 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.
Actual Study Start Date : February 22, 2016
Estimated Primary Completion Date : August 22, 2018
Estimated Study Completion Date : October 22, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis

Arm Intervention/treatment
Experimental: Group 1
200 mg roscovitine (8) or placebo (4) once daily for 4 cycles of 7 days (4 days "on" and 3 days "off")
Drug: Roscovitine
Roscovitine is an experimental drug candidate in the family of pharmacological cyclin-dependent kinase (CDK) inhibitors that preferentially inhibit multiple enzyme targets including CDK2, CDK7 and CDK9. Seliciclib is a 2,6,9-substituted purine analog.
Other Names:
  • Seliciclib
  • CYC202

Drug: Placebo
The placebo treatment is lactose capsule.

Experimental: Group 2
400 mg roscovitine (8) or placebo (4) once daily for 4 cycles of 7 days (4 days "on" and 3 days "off")
Drug: Roscovitine
Roscovitine is an experimental drug candidate in the family of pharmacological cyclin-dependent kinase (CDK) inhibitors that preferentially inhibit multiple enzyme targets including CDK2, CDK7 and CDK9. Seliciclib is a 2,6,9-substituted purine analog.
Other Names:
  • Seliciclib
  • CYC202

Drug: Placebo
The placebo treatment is lactose capsule.

Experimental: Group 3
400 mg roscovitine (8) or (4) placebo twice daily for cycles of 7 days (4 days "on" and 3 days "off")
Drug: Roscovitine
Roscovitine is an experimental drug candidate in the family of pharmacological cyclin-dependent kinase (CDK) inhibitors that preferentially inhibit multiple enzyme targets including CDK2, CDK7 and CDK9. Seliciclib is a 2,6,9-substituted purine analog.
Other Names:
  • Seliciclib
  • CYC202

Drug: Placebo
The placebo treatment is lactose capsule.




Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. Change in the concentration of Pseudomonas Aeruginosa [ Time Frame: 3 months ]
    Change in the concentration (CFU/mL) of Pseudomonas aeruginosa in the sputum at each visit from V1 (Screening) up to V7 (Completion Visit).

  2. PK parameters [ Time Frame: 3 months ]
    PK parameters: Maximum Concentration (Cmax), Time to reach Cmax (Tmax), Area Under Curve (AUCt and AUCInf), Half-life (t1/2) for roscovitine and its M3 metabolite.

  3. Pro- and anti-inflammatory cytokines [ Time Frame: 3 months ]
    Monitoring the levels of pro- and anti-inflammatory cytokines, in particular: interleukin (IL)-17A, IL-5, IFN-γ, IL-1 receptor antagonist, IL-4, IL-6, IL-10, tumor necrosis factor-alpha, and IL-18 on V2, V3 and V7 (Completion Visit)

  4. C-reactive protein [ Time Frame: 3 months ]
    Change in C-reactive protein (CRP) at each visit from V1 (Screening) up to V7 (Completion)

  5. Cystic Fibrosis Questionnaire-Revised [ Time Frame: 3 months ]
    Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) at each visit from V1 up to V8 (Safety Follow-up)

  6. Body Mass Index [ Time Frame: 3 months ]
    Change in body mass index (BMI) at each visit from V1 (Screening) up to V7 (Completion Visit)

  7. Forced expiratory volume in 1 second [ Time Frame: 3 months ]
    Change in forced expiratory volume in 1 second (FEV1) at each visit from V1 (Screening) up to V7 (Completion Visit)

  8. Sweat Chloride Concentration [ Time Frame: 3 months ]
    Change in Sweat Chloride Concentration at V2, V3, V5 and V7 (Completion)

  9. Nasal Potential Difference [ Time Frame: 3 months ]
    Change in Nasal Potential Difference (NPD) at V1 (Screening) and V6 (for patients included in Paris Cochin CF Center)

  10. Pain questionnaire [ Time Frame: 3 months ]
    Evaluate of the pain and of the impact of the pain in patients with cystic fibrosis



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02649751


Contacts
Contact: Gilles RAULT, MD gilles.rault@perharidy.fr
Contact: Laëtitia GUEGANTON laetitia.gueganton@perharidy.fr

Locations
France
CHR - Hôpital Calmette Recruiting
Lille, France, 59037
Contact: Anne PREVOTAT, Dr    03 20 44 59 62    anne.prevotat@chru-lille.fr   
CH Lyon Sud Recruiting
Lyon, France, 69495
Contact: Isabelle DURIEU, Dr    04 78 86 13 52    isabelle.durieu@chu-lyon.fr   
Hôpital Arnaud de Villeneuve Recruiting
Montpellier, France, 34295
Contact: Raphaël CHIRON, Dr    04 67 33 60 89    r-chiron@chu-montpellier.fr   
CHU Nantes Recruiting
Nantes, France, 44093
Contact: Isabelle DANNER-BOUCHER, Dr    02 40 16 52 67    isabelle.danner@chu-nantes.fr   
CHU de Nice - Hôpital Pasteur Recruiting
Nice, France, 06001
Contact: Sylvie LEROY, MD         
Hôpital Cochin Recruiting
Paris, France, 75014
Contact: Dominique HUBERT, Dr    01 58 41 23 78    dominique.hubert@cch.aphp.fr   
CHU de Bordeaux - Hôpital Haut-Lévêque Recruiting
Pessac, France, 33604
Contact: Julie MACEY, MD         
Centre de Ressources et de Compétences de la mucoviscidose Recruiting
Reims, France, 51100
Contact: Bruno RAVONINJATOVO    03 26 78 38 68      
Centre de Perharidy Recruiting
Roscoff, France, 29684
Contact: Gilles RAULT, Dr    02 98 29 39 15    gilles.rault@perharidy.fr   
Hôpital Foch Active, not recruiting
Suresnes, France, 92150
Hôpital Larrey Recruiting
Toulouse, France, 30030
Contact: Marlène MURRIS-ESPIN, Dr    05 61 32 28 57    murris.m@chu-toulouse.fr   
Centre Hospitalier Bretagne Atlantique Recruiting
Vannes, France, 56017
Contact: Sandrine HUGE, Dr    0297014756 ext +33    sandrine.huge@ch-bretagne-atlantique.fr   
Sponsors and Collaborators
University Hospital, Brest
ManRos Therapeutics
Cyclacel Pharmaceuticals, Inc.
Investigators
Principal Investigator: Gilles RAULT, MD Centre de Pérharidy - Roscoff

Responsible Party: University Hospital, Brest
ClinicalTrials.gov Identifier: NCT02649751     History of Changes
Other Study ID Numbers: RB 15.098 (ROSCO CF)
First Posted: January 7, 2016    Key Record Dates
Last Update Posted: April 4, 2018
Last Verified: April 2018

Keywords provided by University Hospital, Brest:
Cystic Fibrosis
Roscovitine
Seliciclib
CYC202

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Roscovitine
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action