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

NCT02649751 | Terminated Phase 2 DMC

• 1 other identifier: RB 15.098 (ROSCO CF)
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 11

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.

Conditions

Cystic Fibrosis

Keywords

Cystic Fibrosis; Roscovitine; Seliciclib; CYC202

Outcome Measures

Primary Outcomes (1)

• Safety of increasing doses of Roscovitine

  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

  3 months

Secondary Outcomes (10)

• Change in the concentration of Pseudomonas Aeruginosa

  3 months

• PK parameters

  3 months

• Pro- and anti-inflammatory cytokines

  3 months

• C-reactive protein

  3 months

• Cystic Fibrosis Questionnaire-Revised

  3 months

Study Arms (3)

Group 1

EXPERIMENTAL

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

Drug: Roscovitine; Drug: Placebo

Group 2

EXPERIMENTAL

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

Drug: Roscovitine; Drug: Placebo

Group 3

EXPERIMENTAL

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

Drug: Roscovitine; Drug: Placebo

Interventions

Roscovitine 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.

Also known as: Seliciclib, CYC202

Group 1; Group 2; Group 3

Placebo DRUG

The placebo treatment is lactose capsule.

Group 1; Group 2; Group 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Brest: lead
• ManRos Therapeutics: collaborator
• Cyclacel Pharmaceuticals, Inc.: collaborator

Study Sites (11)

CHU de Nice - Hôpital Pasteur

Nice, France, 06001, France

Location

CHU de Bordeaux - Hôpital Haut-Lévêque

Pessac, France, 33604, France

Location

Centre de Ressources et de Compétences de la mucoviscidose

Reims, France, 51100, France

Location

Centre Hospitalier Bretagne Atlantique

Vannes, France, 56017, France

Location

CHR - Hôpital Calmette

Lille, 59037, France

Location

CH Lyon Sud

Lyon, 69495, France

Location

Hôpital Arnaud de Villeneuve

Montpellier, 34295, France

Location

CHU Nantes

Nantes, 44093, France

Location

Hôpital Cochin

Paris, 75014, France

Location

Centre de Perharidy

Roscoff, 29684, France

Location

Hôpital Larrey

Toulouse, 30030, France

Location

Related Publications (1)

• Meijer L, Hery-Arnaud G, Leven C, Nowak E, Hillion S, Renaudineau Y, Durieu I, Chiron R, Prevotat A, Fajac I, Hubert D, Murris-Espin M, Huge S, Danner-Boucher I, Ravoninjatovo B, Leroy S, Macey J, Urban T, Rault G, Mottier D, Berre RL. Safety and pharmacokinetics of Roscovitine (Seliciclib) in cystic fibrosis patients chronically infected with Pseudomonas aeruginosa, a randomized, placebo-controlled study. J Cyst Fibros. 2022 May;21(3):529-536. doi: 10.1016/j.jcf.2021.10.013. Epub 2021 Dec 24.

  PMID: 34961705 RESULT

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

Roscovitine

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Intervention Hierarchy (Ancestors)

Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Gilles RAULT, MD

  Centre de Pérharidy - Roscoff

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2016
• First Posted: January 7, 2016
• Study Start: February 22, 2016
• Primary Completion: July 26, 2018
• Study Completion: July 26, 2018
• Last Updated: December 12, 2025

Record last verified: 2018-07

Locations

FR (11)