Trial to Evaluate Efficacy and Safety of Lenabasum in Cystic Fibrosis

Cystic Fibrosis Clinical Trial

Official title:

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial to Evaluate Efficacy and Safety of Lenabasum in Cystic Fibrosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03451045
• Other study ID #: JBT101-CF-002
• Status: Completed
• Phase: Phase 2
• Start date: December 22, 2017
• Est. completion date: June 17, 2020

Study information

• Verified date: December 2022
• Source: Corbus Pharmaceuticals Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 2 multicenter, double-blind, randomized, placebo-controlled study assessing the efficacy and safety of lenabasum for the treatment of cystic fibrosis in patients 12 years of age or older. Approximately 415 subjects will be enrolled in this study at about 100 sites in North America, and Europe. The planned duration of treatment with study drug is 28 weeks.

Study drug will be lenabasum 20 mg BID, lenabasum 5 mg BID, and placebo in a 2:1:2 ratio.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 447
• Est. completion date: June 17, 2020
• Est. primary completion date: June 17, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

1. = 12 years of age at the time Informed Consent/ Assent is signed.

2. Weight = 40 kg.

3. FEV1 = 40% predicted and < 100% predicted in the last 12 months.

4. Physician-initiated treatment with an IV antibiotic 2 or 3 times in the last 12 months for a new PEx or physician-initiated treatment with an IV antibiotic 1 time in the last 12 months plus physician-initiated treatment with oral antibiotic(s) 1 or more times in the past 12 months for a new PEX.

Exclusion Criteria:

1. Severe or unstable CF at screening or Visit 1.

2. Any of the following values for laboratory tests at screening:

1. A positive pregnancy test.

2. Hemoglobin < 10 g/dL in males and < 9 g/dL in females.

3. Neutrophils < 1.0 x 10^9 /L.

4. Platelets < 75 x 10^9/L.

5. Creatinine clearance < 50 mL/min according to Modification of Diet in Renal Disease (MDRD) Study equation.

6. Serum transaminases > 2.5 x upper limit of normal.

3. Any medical condition or concurrent medical therapies at screening or Visit 1 that may put the subject at greater safety risk, influence response to study drug or interfere with study assessments.

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• Lenabasum 20 mg
Subjects will receive lenabasum 20 mg twice daily.
• Lenabasum 5 mg
Subjects will receive lenabasum 5 mg twice daily.

Other:
• Placebo
Subjects will receive placebo twice daily.

Locations

Country	Name	City	State
Austria	Cystic Fibrosis Centre Innsbruck Medical University of Innsbruck, Dept. for Child and Adolescent Health, University Clinic for Paediatrics, Cardiology, Pneumology, Allergology, Cystic Fibrosis	Innsbruck
Austria	Medical University of Vienna	Vienna
Belgium	Universitair Ziekenhuis Brussel	Brussels
Bulgaria	Medical Center Prolet EOOD	Ruse
Bulgaria	UMHAT Alexandrovska	Sofia
Bulgaria	MHAT Sveta Marina EAD	Varna
Canada	Centre hospitalier de l'Université de Montréal (CHUM)	Montréal
Canada	St. Michael's Hospital	Toronto
Canada	The Hospital for Sick Children	Toronto
Canada	St. Paul's Hospital	Vancouver
Czechia	Motol University Hospital	Praha
France	Centre de Référence de la Mucoviscidose	Bron
France	Service de Pneumologie, Allergologie, Mucoviscidose; Hôpital Femme-Mère-Enfant	Bron
France	Service de Pediatrie Medico-Chirurgicale et Genetique	Dijon
France	CHRU de Montpellier	Montpellier
France	CRCM Enfant de Nancy	Nancy
France	CHU de Nice	Nice
France	Centre de Recherche en Explorations Fonctionnelles (CREF)	Paris
France	CRCM Hôpital Necker	Paris
France	Foundation ILDYS	Roscoff
France	Nouvel Hopital Civil Strasbourg	Strasbourg
Germany	Charité Universitätsmedzin	Berlin
Germany	Catholic Hospital Bochum - St. Josef-Hospital	Bochum
Germany	University Hospital Essen	Essen
Germany	University Medicine Essen Ruhrlandklinik	Essen
Germany	Goethe University Children´s Hospital	Frankfurt
Germany	Hannover Medical School	Hanover
Germany	University Hospital Jena	Jena
Germany	Klinikum der Ludwig Maximilian Universität München	München
Greece	General Hospital of Thessaloniki Ippokratio	Thessaloníki
Hungary	National Koranyi Institute of Pulmonology, Department of Cystic Fibrosis	Budapest
Hungary	University of Debrecen - Kenezy Gyula University Hospital	Debrecen
Hungary	Bács-Kiskun County Hospital, Teaching Hospital of the University of Szeged	Kecskemét
Hungary	Moritz Kaposi General Hospital, Mosdós, Department of Pediatric Pulmonary Rehabilitation	Mosdós
Hungary	Pediatric Pulmonology, Törökbálint, Hungary	Torokbalint
Italy	Centro Regionale Toscano di Riferimento per la Fibrosi Cistica	Firenze
Italy	U.O.S.D. - Centro fibrosi cistica	Genova
Italy	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico	Milano
Italy	Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico	Milano
Italy	Azienda Ospedaliera Universitaria Verona	Verona
Netherlands	Radbound UMC	Nijmegen
Poland	Instytut Matki I Dziecka, Centrum Leczenia Mukowiscydozy - Oddzial Chorob Pluc	Dziekanow Lesny
Poland	Oddzial Pediatrii z Pododdzialem Leczenia Mukowiscydozy	Gdansk
Poland	Instytut Gruzlicy I Chorob Pluc Oddzial Terenowy im Jana I Ireny Rudnikow	Rabka-Zdrój
Poland	Institute for Mother and Child, Department of CF for Children's and Youth	Rzeszów
Portugal	Hospital de Santa Maria	Lisboa
Romania	Medial Center for Ambulatory Diagnosis and Treatment	Brasov
Russian Federation	Scientfic Research Institute of Pulmonology	Moscow
Russian Federation	Diagnostic Children Hospital, Department of Pediatrics and Adolescent Medicine, Department of Pediatric Pulmonary, Allergology and Endocrinology	Mytishchi
Russian Federation	Children's City Hospital of Saint Olga	Saint Petersburg
Russian Federation	First St. Petersburg State Pavlov Medical University	St. Petersburg
Serbia	Clinical for Pulmonary Diseases, Clinical Center of Serbia	Belgrade
Serbia	Institute for Child and Youth Health Care of Vojvodina	Novi Sad
Serbia	Institute for Pulmonary Disease of Vojvodina	Sremska Kamenica
Slovakia	Children's faculty hospital with polyclinic Banska Bystrica	Banská Bystrica
Slovakia	Children's Faculty Hospital Kosice	Košice
Spain	Unidad de Fibrosis Quistica Adultos	Barcelona
Spain	Unidad de Fibrosis Quistica Pediatria	Barcelona
Spain	Unidad de Fibrosis Quistica y Transplante Pulmonar	Valencia
Sweden	Skane University Hospital	Lund
Sweden	Karolinska University Hospital	Stockholm
United Kingdom	Belfast City Hospital	Belfast	Northern Ireland
United Kingdom	Birmingham Women's and Children's NHS Foundation Trust	Birmingham
United Kingdom	University Hospitals Birmingham NHS Foundation Trust	Birmingham
United Kingdom	Royal Papworth Hospital NHS Foundation Trust	Cambridge
United Kingdom	Liverpool Heart and Chest Hospital	Liverpool	Merseyside
United Kingdom	Cardiff and Vale University Health Board	Llandough
United Kingdom	Barts Health NHS Trust	London
United Kingdom	Royal Brompton & Harefield NHS Foundation Trust	London
United Kingdom	Wolfson Cystic Fibrosis Centre City Hospital Campus	Nottingham
United Kingdom	University Hospital Southampton NHS Foundation Trust	Southampton
United States	Emory Children's Center	Atlanta	Georgia
United States	Johns Hopkins University	Baltimore	Maryland
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	UT Southwestern Medical Center	Dallas	Texas
United States	National Jewish Health	Denver	Colorado
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	The Cystic Fibrosis Institute	Glenview	Illinois
United States	New York Medical College	Hawthorne	New York
United States	Milton S. Hershey Medical Center / Penn State College of Medicine	Hershey	Pennsylvania
United States	Texas Children's Hospital	Houston	Texas
United States	Dartmouth-Hitchcock Medical Center (main location)	Lebanon	New Hampshire
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Miller Children's Hospital	Long Beach	California
United States	University Hospital and UW Health Clinics	Madison	Wisconsin
United States	Dartmouth-Hitchcock Manchester (satellite site)	Manchester	New Hampshire
United States	University of Miami	Miami	Florida
United States	Atlantic Health Children's Hospital	Morristown	New Jersey
United States	Rutgers Robert Wood Johnson Medical School	New Brunswick	New Jersey
United States	North Shore LIJ Health System	New Hyde Park	New York
United States	Mount Sinai Beth Israel	New York	New York
United States	Central Florida Pulmonary Group, PA	Orlando	Florida
United States	Drexel University College of Medicine	Philadelphia	Pennsylvania
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	University of Utah	Salt Lake City	Utah
United States	Sanford Children's Specialty Clinic	Sioux Falls	South Dakota
United States	USF Center for Advance Lung Disease	Tampa	Florida
United States	The University of Texas Health Science Center at Tyler	Tyler	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Corbus Pharmaceuticals Inc.	Cystic Fibrosis Foundation

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Bulgaria,  Canada,  Czechia,  France,  Germany,  Greece,  Hungary,  Italy,  Netherlands,  Poland,  Portugal,  Romania,  Russian Federation,  Serbia,  Slovakia,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pulmonary Exacerbation (PEx) Rate Over 28 Weeks	Rate of PEx using the primary PEx definition with lenabasum 20 mg BID compared to placebo, during the treatment period. An primary PEx is defined on the physician's decision to treat with oral, intraveneous or inhaled antibiotics in the presence 4/12 Fuch's criteria (Change in sputum, new/increased hemoptysis, increased cough, increased dyspnea, malaise, fatigue/lethargy, Temperature greater than 38C, weight loss, sinus pain, change in sinus discharge, change in exam of chest, decrease in FEV1 of more than 10%, radiographic change). This excludes prophylactic antibiotics. A new PEx is a one that occurs at 28 days after the previous PEx.	28 weeks (Baseline Day 0 to Week 28)
Secondary	Pulmonary Exacerbation (PEx) Rate	Event rate of PEx using the secondary PEx definition with lenabasum 20 mg BID compared to placebo. The secondary definition of a PEx is based on the physician's diagnosis of pulmonary exacerbation and commencement of new oral, intravenous, or inhaled antibiotics. A new PEx is defined one that starts 28 or more days after the previous confirmed PEx. The PEx rate is calculated as the number of PEx/28 weeks	28 weeks (Baseline Day 0 to Week 28)
Secondary	Time to First New Pulmonary Exacerbation (PEx)	Time to first new PEx using the primary PEx definition with lenabasum 20 mg BID compared to placebo. An primary PEx is defined on the physician's decision to treat with oral, intraveneous or inhaled antibiotics in the presence 4/12 Fuch's criteria (Change in sputum, new/increased hemoptysis, increased cough, increased dyspnea, malaise, fatigue/lethargy, Temperature greater than 38C, weight loss, sinus pain, change in sinus discharge, change in exam of chest, decrease in FEV1 of more than 10%, radiographic change). This excludes prophylactic antibiotics. A new PEx is a one that occurs at 28 days after the previous PEx. The rate is calculate over a 28 week period from visit 1 to week 28 visit	28 weeks (Baseline Day 0 to Week 28)
Secondary	Pulmonary Exacerbation (PEx)	Time to first PEx using the secondary PEx definition with lenabasum 20 mg BID compared to placebo. The secondary definition of a PEx is based on the physician's diagnosis of pulmonary exacerbation and commencement of new oral, intravenous, or inhaled antibiotics. A new PEx is defined one that starts 28 or more days after the previous confirmed PEx.	28 weeks (Baseline Day 0 to Week 28)
Secondary	CFQ-R Respiratory Symptom Domain	Cystic Fibrosis Questionnaire - Revised measures change from baseline in CFQ-R respiratory symptom domain with lenabasum compared to placebo. Subjects >/= 14 years of age. 5 distinct 4-point Likert scales (e.g., always/often/ sometime/never) Scores for each HRQoL domain; after recoding, each item is summed to generate a domain score and standardized. Scores range from 0 to 100, with higher scores indicating better health.	28 weeks (Change from Baseline Day 0 to Week 28)
Secondary	FEV1 % Predicted	Change from baseline to week 28 in Forced Expiratory Volume in 1 second (FEV1) expressed as a percentage of a normal range. A lower percentage FEV1 is indicative of decrease in lung functionality. The changes observed from baseline to week 28 for lenabasum will be compared with those observed for placebo treated participants.	28 weeks (Change from Baseline Day 0 to Week 28)