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

NCT ID: NCT02649751

Last Updated: 2018-12-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-22
• Study Completion Date: 2018-07-26

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.

Conditions

Cystic Fibrosis

Keywords

Cystic Fibrosis; Roscovitine; Seliciclib; CYC202

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Group 1

200 mg roscovitine (8) or placebo (4) once daily for 4 cycles of 7 days (4 days "on" and 3 days "off")

Group Type: EXPERIMENTAL

Roscovitine

Intervention Type: DRUG

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.

Placebo

Intervention Type: DRUG

The placebo treatment is lactose capsule.

Group 2

400 mg roscovitine (8) or placebo (4) once daily for 4 cycles of 7 days (4 days "on" and 3 days "off")

Group Type: EXPERIMENTAL

Roscovitine

Intervention Type: DRUG

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.

Placebo

Intervention Type: DRUG

The placebo treatment is lactose capsule.

Group 3

400 mg roscovitine (8) or (4) placebo twice daily for cycles of 7 days (4 days "on" and 3 days "off")

Group Type: EXPERIMENTAL

Roscovitine

Intervention Type: DRUG

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.

Placebo

Intervention Type: DRUG

The placebo treatment is lactose capsule.

Interventions

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.

Intervention Type: DRUG

Placebo

The placebo treatment is lactose capsule.

Intervention Type: DRUG

Other Intervention Names

Seliciclib; CYC202

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;
• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ManRos Therapeutics

UNKNOWN

Sponsor Role: collaborator

Cyclacel Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: collaborator

University Hospital, Brest

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilles RAULT, MD

Role: PRINCIPAL_INVESTIGATOR

Centre de Pérharidy - Roscoff

Locations

CHR - Hôpital Calmette

Lille, , France

CH Lyon Sud

Lyon, , France

Hôpital Arnaud de Villeneuve

Montpellier, , France

CHU Nantes

Nantes, , France

CHU de Nice - Hôpital Pasteur

Nice, , France

Hôpital Cochin

Paris, , France

CHU de Bordeaux - Hôpital Haut-Lévêque

Pessac, , France

Centre de Ressources et de Compétences de la mucoviscidose

Reims, , France

Centre de Perharidy

Roscoff, , France

Hôpital Larrey

Toulouse, , France

Centre Hospitalier Bretagne Atlantique

Vannes, , France

Countries

France

Other Identifiers

RB 15.098 (ROSCO CF)

Identifier Type: -

Identifier Source: org_study_id