Lancovutide (Moli1901) Inhalation Solution Study in Adolescents and Adults With Cystic Fibrosis

A Randomized, Double-Blind, Placebo-Controlled, Dose-finding Study to Evaluate the Efficacy and Safety of Aerosolized Moli1901 in Adolescents (12 Years of Age or Older) and Adults With Cystic Fibrosis

This is a dose-finding study for the investigational product Lancovutide (Moli1901) in the exploratory phase IIb to establish minimum effective dose, optimal dose, and maximum safe dose. Additionally, the tolerability of Moli1901 shall be investigated.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: Moli1901; Drug: Moli1901 placebo

Detailed Description

Study Moli1901-010B is a multi center, parallel group, placebo controlled, double-blind efficacy and safety evaluation of three different dosage schedules of aerosolized Moli1901 in adolescents (12 years of age or older), and adults. Study will start with a screening period (visit 1) followed by an 8 weeks double blind comparative treatment period (visit 2-7). Thereafter, subjects will be observed for additional 4 weeks without treatment (follow-up period and visit 8). Spirometry, pulse oximetry and other safety measurements will be performed up to 120 min after study medication inhalation. The study will be conducted in 30 sites in 9 European countries.

• Study Type: Interventional
• Enrollment (Anticipated): 160
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8086
    • Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Body mass index
• Confirmed diagnosis of cystic fibrosis
• FEV1 between 50% and 85% of predicted
• Oxygen saturation level measured by pulse oximetry (SpO2) >90 % on room air

Exclusion Criteria:

• Bronchial hyperresponsiveness
• Unstable lung function
• Pulmonary disease such as pneumonia, tuberculosis, or lung cancer
• Acute upper respiratory tract infection within the last 2 weeks
• Acute lower respiratory tract infection (requiring antibiotics or hospitalization) within the last 4 weeks
• Pulmonary exacerbation within the last 4 weeks
• Changes from routine maintenance therapy within the last 4 weeks
• Scheduled changes to inhaled antibiotics regimen during the course of the study
• Receive or are planned to receive any treatment via "on-off" regimen (e.g. Tobramycin - TOBI®); last dose of any "on-off" treatment within the last 6 weeks
• Any clinically significant liver, renal, cardiac, neurological, or hematological disease
• ABPA or colonization with Burkholderia cepacia
• Poorly controlled diabetes mellitus

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; daily inhalation	Drug: Moli1901; 2,5 ml inhalation solution, 8 weeks treatment period; Other Names: Lancovutide, 2622U90, duramycin
Experimental: 2; inhalation every other day	Drug: Moli1901; 2,5 ml inhalation solution, 8 weeks treatment period; Other Names: Lancovutide, 2622U90, duramycin
Experimental: 3; inhalation twice a week	Drug: Moli1901; 2,5 ml inhalation solution, 8 weeks treatment period; Other Names: Lancovutide, 2622U90, duramycin
Placebo Comparator: 4; daily inhalation	Drug: Moli1901 placebo; 2,5 ml placebo solution, 8 weeks treatment period

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The change in the percentage of the predicted FEV1 (forced expiratory volume in first second) value	at every study visit

Secondary Outcome Measures

Outcome Measure	Time Frame
The ensemble of two subject reported clinical scores, which are physical dimensions of the self-report, disease-specific quality of life test, the cystic fibrosis questionnaire in the revised version	every 2 weeks

Collaborators and Investigators

• Sponsor: AOP Orphan Pharmaceuticals AG
• Investigators: Principal Investigator: Ernst Eber, Prof Dr, Medical University of Graz

Publications and helpful links

General Publications

• Grasemann H, Stehling F, Brunar H, Widmann R, Laliberte TW, Molina L, Doring G, Ratjen F. Inhalation of Moli1901 in patients with cystic fibrosis. Chest. 2007 May;131(5):1461-6. doi: 10.1378/chest.06-2085.
• Zeitlin PL, Boyle MP, Guggino WB, Molina L. A phase I trial of intranasal Moli1901 for cystic fibrosis. Chest. 2004 Jan;125(1):143-9. doi: 10.1378/chest.125.1.143.
• Rickert DE, Dingley K, Ubick E, Dix KJ, Molina L. Determination of the tissue distribution and excretion by accelerator mass spectrometry of the nonadecapeptide 14C-Moli1901 in beagle dogs after intratracheal instillation. Chem Biol Interact. 2005 Jun 30;155(1-2):55-61. doi: 10.1016/j.cbi.2005.04.002.
• McNulty MJ, Hutabarat RH, Findlay JW, Devereux K, Knick VC, Harvey RJ, Molina L. Pharmacokinetics and tissue distribution of the nonadecapeptide Moli1901 in rats and mice. Xenobiotica. 2003 Feb;33(2):197-210. doi: 10.1080/0049825021000022320.
• Zebedin E, Koenig X, Radenkovic M, Pankevych H, Todt H, Freissmuth M, Hilber K. Effects of duramycin on cardiac voltage-gated ion channels. Naunyn Schmiedebergs Arch Pharmacol. 2008 Mar;377(1):87-100. doi: 10.1007/s00210-007-0248-5. Epub 2008 Jan 5.
• Eber E, Trawinska-Bartnicka M, Sands D, Bellon G, Mellies U, Bolbas K, Quattrucci S, Mazurek H, Widmann R, Schoergenhofer C, Jilma B, Ratjen F. Aerosolized lancovutide in adolescents (>/=12 years) and adults with cystic fibrosis - a randomized trial. J Cyst Fibros. 2021 Jan;20(1):61-67. doi: 10.1016/j.jcf.2020.08.014. Epub 2020 Sep 1.

Helpful Links

• Sponsor
• North American Cystic Fibrosis Conference

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): July 1, 2009
• Study Completion (Actual): July 1, 2009

Study Registration Dates

• First Submitted: April 30, 2008
• First Submitted That Met QC Criteria: May 2, 2008
• First Posted (Estimate): May 5, 2008

Study Record Updates

• Last Update Posted (Estimate): August 27, 2009
• Last Update Submitted That Met QC Criteria: August 26, 2009
• Last Verified: August 1, 2009

More Information

Terms related to this study

• Keywords: lung; cystic fibrosis; Moli1901; Lancovutide; 2622U90; duramycin
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: Moli1901-010B; EudraCT No 2006-006693-24