Study Results and Completed Trials

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial To Evaluate Efficacy And Safety Of Lenabasum In Cystic Fibrosis
Lenabasum (JBT-101) is a novel oral drug designed to reduce inflammation and prevent permanent tissue damage in the lungs. The results from a small Phase 2 clinical trial suggested that Lenabasum treatment showed markers of reduced inflammation. Following this study, a multinational double-blind, randomized, placebo-controlled study was employed to evaluate the safety and efficacy of Lenbasum. However, this large Phase 2b trial did not find a statistically significant reduction in the rate of pulmonary exacerbations in CF patients at high risk for recurrent pulmonary exacerbations between those who took lenabausm and those who took placebo. While, the study failed to meet its primary endpoint, the results from the trial suggest that Lenabasum’s use was safe and well-tolerated.
Clinical Trial Details | Press Release

A Phase 3 Study Of VX-445 Combination Therapy In Cystic Fibrosis (CF) Subjects Heterozygous For F508del And A Gating Or Residual Function Mutation (F/G And F/RF Genotypes)
This study enrolled patients who have DF508 and a mutation that is responsive to either ivacaftor or tezacaftor/ivacaftor to see if there is additional benefit with the elezacaftor/tezacaftor/ivacaftor combination ontop of standard of care. The results of this study will be posted here when they are published.
Clinical Trial Details

Pilot Study Of The In Vivo Efficacy Of Tobramycin Inhalation Powder (TIP) In Cystic Fibrosis Patients Infected With Burkholderia Cepacia Complex
Burkholderia cepacia complex is resistant to many antibiotics and thus is difficult to treat. Currently, there is no effective suppressive therapy for those chronically infected with B. cepacia complex. The purpose of this open-label pilot study was to see if an approved antibiotic called tobramycin was effective against a chronic B. cepacia complex infection in patients with CF when administered as an inhalation powder via Podhaler. After 28 days of tobramycin inhalation powder (TIP) treatment, the study saw a significant reduction in sputum B. cepacia complex density and pulmonary inflammatory markers which suggest TIP may be effective. However, there was no statistically significant increase in lung function seen at the end of the study period.
Clinical Trial Details | Published Results

A Phase 3 Study Of VX-659 Combination Therapy In Subjects With Cystic Fibrosis Heterozygous For The F508del Mutation And A Minimal Function Mutation (F/MF): A Study Evaluating The Long Term Safety And Efficacy Of VX-659 Combination Therapy
This phase 3 study enrolled patients who had one F508del with a minimal function mutation. At the time of the study there were no approved CFTR modulator treatments for patients who had one copy of the F508del CFTR mutation and a minimal-function CFTR mutation. VX-659 was one of two “2nd generation” CFTR correctors in development by Vertex Pharmaceuticals. Although, the phase 3 trial with VX-659 in combination with tezacaftor and ivacaftor study showed improvement across all study endpoints, ultimately this compound was not selected for further development. You can read more about this decision in a press release issued by Vertex. There will be no additional publications made regarding the results of the phase 3 trial.
Clinical Trial Details | Press Release

Trial To Evaluate Efficacy And Safety Of Lenabasum In Cystic Fibrosis
This trial was a phase 2 trial evaluating whether or not an oral, anti-inflammatory drug called lenabausm was effective in reducing pulmonary exacerbations in patients with CF. Results will be shared when available.
Clinical Trial Details

An Efficacy And Safety Study Of SPX-101 Inhalation Solution In Subjects With Cystic Fibrosis (HOPE-1)
The purpose of this phase two study was to test the safety and effectiveness of SPX-101, an ENaC inhibitor or a compound that blocks the function of the sodium channels. By blocking these sodium channels, SPX-101 was predicted to help maintain fluid within the airways to improve mucus clearance. However, the results of this clinical trial were not statistically significant. SPX-101 will not be studied any further so no further publications will be available for the trial.
Clinical Trial Details | Summary

EMPIRE CF: A Phase 2 Study To Evaluate The Efficacy, Safety, And Tolerability Of CTX-4430 In Adult CF Patients
Acebilustat (formerly known as CTX-4430) is an oral anti-inflammatory drug thought to prevent permanent tissue damage in the lungs. In doing so, it has the potential to minimize lung function decline and pulmonary exacerbations in patients with CF. The primary purpose of this phase 2, multicenter study was to evaluate acebilustat’s safety and effect on lung function in people with CF. In order to determine acebilustat’s effectiveness, this study used a randomized, double-blind, and placebo-controlled design, meaning some participants received the study drug, and others received a placebo without knowing which drug assignment they were receiving. The results of this study have not been published yet; however this section will be updated when they are available
Clinical Trial Details | Demographic Study

Early Signs Of Efficacy Study With Riociguat In Adult Homozygous Delta F508 Cystic Fibrosis Patients
The study drug, riociguat (BAY63-2521), is a drug that is approved to treat pulmonary hypertension. However, preclinical lab based studies suggested that this drug had the potential to improve the function of the CFTR protein. The purpose of this multicenter phase 2 study was to assess the safety, tolerability and efficacy of oral riociguat in adults with two copies of the F508del mutation. In order to find early signs of the drug’s effectiveness, this randomized, double-blind, placebo-controlled study measured and compared the sweat chloride of participants who received riociguat to participants who received a placebo. However, this study was terminated as it was no longer considered appropriate. The results can be found on clinicaltrials.gov. No further publications will be available for this trial.
Clinical Trial Details | Summary

A Study Evaluating The Safety And Efficacy Of VX-440 Combination Therapy In Subjects With Cystic Fibrosis
VX-440 in combination with tezacaftor and ivacaftor is no longer in development by Vertex Pharmaceuticals.
Clinical Trial Details | Summary  | Press Release

A Phase 1, Single-Center, Open-Label Safety Study Of SPX-101 Inhalation Solution In Subjects With Cystic Fibrosis
The focus of this phase 1 study was to test safety of SPX-101, a new drug that blocks sodium channels to help maintain fluid within the airways which improves mucus clearance. The results of the study demonstrate that SPX-101 inhalation solution was well-tolerated at a variety of doses by healthy adults and adults with CF. So the results from this first human study support further investigation of this CF treatment.
Clinical Trial Details | Published Results

A Phase 3 Study Of VX-661 In Combination With Ivacaftor In Subjects Aged 12 Years And Older With Cystic Fibrosis, Who Have One F508del-CFTR Mutation And A Second Mutation That Has Been Demonstrated To Be Clinically Responsive To Ivacaftor (VX14-661-109)
The aim of this phase 3 trial was to see if tezacaftor in addition to ivacaftor provided any clinical benefit in patients who had a mutation that was known to respond to ivacaftor (for example, the G551D mutation.) The study did not meet its primary endpoint of absolute change in percent predicted forced expiratory volume in one second from baseline through 8 weeks and based on this data no further regulatory approvals for tezacaftor/ivacaftor in this CF population will be applied for by Vertex.
Clinical Trial Details | Press Release

A Phase 3 Study To Evaluate The Efficacy And Safety Of Ivacaftor And VX-661 In Combination With Ivacaftor In Subjects Aged 12 Years And Older With Cystic Fibrosis, Heterozygous For The F508del-CFTR Mutation (VX14-661-108)
This phase 3 study demonstrated the safety and efficacy for Symdeko in people with CF who have one copy of the F508del mutation with a residual function mutation. The results were submitted to health authorities such as Health Canada to market the drug in Canada. The study drug, tezacaftor (VX-661), is a CFTR corrector or CFTR modulator compound that is designed to move the defective CFTR protein to the proper place on the airway cell surface. When tezacaftor and ivacaftor are used in combination with ivacaftor they can improve ion transport by opening the defective CFTR protein.
Clinical Trial Details | Published Results

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study To Evaluate The Efficacy And Safety Of VX-661 In Combination With Ivacaftor (VX14-661-106)
Like the study described above, this phase 3 trial evaluated the long term efficacy and safety of tezacaftor in combination with ivacaftor in people with cystic fibrosis who have two copies of the DF508 mutation. The results of this study found significant improvements in lung function and a lower rate of pulmonary exacerbation. Since the result of the study deemed tezacaftor–ivacaftor safe and effective, tezacaftor-ivacaftor (Symdeko®) was approved for individuals 12 years and older with two copies of F508del in Canada.
Clinical Trial Details | Published Results

Study Of VX-661 Alone And In Combination With Ivacaftor In Subjects Homozygous Or Heterozygous To The F508del-Cystic Fibrosis Transmembrane Conductance Regulator(CFTR) Mutation (VX11- 661-101)
The Vertex 661-101 study was a Phase 2 clinical trial looking at VX-661 (tezacaftor) and VX-770 (ivacaftor) in CF patients. VX-661 was studied to see if alone or in combination with ivacaftor, it can help decrease some of the effects caused by CF. The study was designed to learn more about the safety and efficacy of VX-661 when given alone and in combination with ivacaftor to people with CF. It also looked at how VX-661 and ivacaftor may affect the body and how the body breaks down and eliminates the drugs. Results from Phase 2 trials like this one, inform decisions on the next phase of clinical trials and what dose might be used.
Clinical Trial Details

Orkambi (Lumacaftor/Ivacaftor) Phase 3 Trial (VX 809-103 Study) And Open Label Extension (VX809-105)
The Vertex 809-103 study was a phase 3 clinical trial looking at a new compound developed by Vertex called lumacaftor (VX-809) in combination with Ivacaftor to target the underlying defect that causes CF by modifying protein function and enhancing ion transport. This drug is now approved by Health Canada for people with two copies of the F508del CF mutation.
Clinical Trial Details | Published Results

G551D Observational Study In Patients Taking Ivacaftor
In 2012, ivacaftor was approved by Health Canada for use in people with one copy of the G551D CFTR mutation. Patients at St. Michael’s Hospital and the Hospital for Sick Children were followed for 2 years after starting on ivacaftor to understand more about how the drug works.

Impact Of CFTR Modulation On Intestinal PH, Motility, And Clinical Outcomes In Patients With Cystic Fibrosis And The G551D Mutation)
Due to a defect in CFTR-mediated bicarbonate secretion, cystic fibrosis is associated with gastrointestinal complications. These complications are marked by an increase in pH and can contribute to dehydration and malnutrition. This study aimed to investigate the effectiveness of ivacaftor treatment on gastrointestinal pH, clinical outcomes, and intestinal transit profiles in patients with the G551D mutation. The focus of this study, ivacaftor, is a drug that acts by holding the gate on the CFTR protein open in order to allow more chloride to flow through and reduce the symptoms of CF. After one month of ivacaftor treatment, the results of this observational study show that ivacaftor improves the proximal small intestinal pH profile in patients with the G551D CFTR mutation and may be related to contemporaneous weight gain.

Cholecalciferol Significantly Increases 25-Hydroxyvitamin D Concentration In Adults With Cystic Fibrosis
The purpose of this study was to determine the prevalence (how many people have a certain disease) of patients with cystic fibrosis that are vitamin D deficient (not receiving enough vitamin D). This study measured the levels of vitamin D in 360 patients and determined that 69% were deficient. The lowest levels of vitamin D were found in patients with lower BMI (body mass index) and lower lung function. After administering cholecalciferol, (vitamin D3, an inactive form of vitamin D), Vitamin D levels increased significantly in 92% of patients
Published Results

NON-THERAPY RELATED TRIALS

Effect Of Pulmonary Exacerbations On Long-Term Lung Function Decline In Cystic Fibrosis
This was a retrospective cohort study which used registry data to understand how pulmonary exacerbations impact rates of decline in lung function.
Published Results

Infection With Burkholderia Cepacia In Cystic Fibrosis Outcome Following Lung Transplantation
Patients who chronically grow Burkholderia cepacia complex in their sputum samples were studied to determine their outcome after lung transplantation. The article discusses outcomes and implications for future treatment for these patient.
Published Results

Exacerbation Frequency And Clinical Outcomes In Adult Patients With Cystic Fibrosis
This study examined how pulmonary exacerbations affect the rate of decline in lung function as well as the time to various clinical outcomes including lung transplant. Researchers examined 446 adult cystic fibrosis patients from Ontario. It was found that having more than 2 exacerbations per year put one at increased risk of a 5% decline in lung function (FEV1).
Published Results

Randomized Controlled Trial Of Biofilm Antimicrobial Susceptibility Testing In Cystic Fibrosis Patients
This randomized controlled trial aimed to determine whether antibiotics chosen based on biofilm antimicrobial susceptibility testing would result in a better microbiologic and clinical response compared to antibiotic chosen based on conventional, planktonic susceptibility testing in the treatment of pulmonary exacerbations in CF patients with chronic P. aeruginosa infection. The result of the study showed that lung function improvements were similar in both groups. Biofilm antimicrobial susceptibility testing did not lead to improved microbiological or clinical outcomes compared to conventional methods in the treatment of pulmonary exacerbations in CF patients with chronic P. aeruginosa.
Published Results

Stenotrophomonas Maltophilia And Cystic Fibrosis Serologic Response And Effect On Lung Disease
Stenotrophomonas maltophilia (aka S. maltophilia) is one of the more common multidrug-resistant organisms associated with respiratory tract infection in patients with CF; however, the effect of chronic S. maltophilia infection on CF lung disease is unclear. So the purpose of this study was to determine the impact of chronic S. maltophilia infection on lung disease in CF. The results of the study demonstrate that patients with chronic S. maltophilia infection have a specific immune response associated with lower lung function. Chronic S. maltophilia infection is also an independent risk factor for pulmonary exacerbations. These results suggest that S. maltophilia can cause infection and negatively affect pulmonary function instead of just colonize the airways which disputes previous literature.
Published Results

Assessing The Impact Of Polymicrobial Pulmonary Infections In CF And Bronchiectasis Via Metagenomics
The metagenome study has been ongoing since 2010. For this study, patients were asked to provide additional sputum samples at clinic visits so that a research lab can identify genetic variants of bacteria and other microorganisms in CF patients.
Below are the links to the abstracts of findings from this study:

  1. Lung microbiota across age and disease state in cystic fibrosis
  2. Phenotypic diversity within a Pseudomonas aeruginosa population infecting an adult with cystic fibrosis
  3. Global analysis of the fungal microbiome in cystic fibrosis patients reveals loss of function of the transcriptional repressor Nrg1 as a mechanism of pathogen adaptation
  4. Selective sweeps and parallel pathoadaptation drive Pseudomonas aeruginosa evolution in the cystic fibrosis lung

Lung Clearance Index Trial With Sick Kids
As a result of improved clinical care, many patients with Cystic Fibrosis (CF) have normal lung function as measured by standard breathing tests (spirometry). This makes it more difficult to evaluate the effect of a therapy on lung function. The Lung Clearance Index (LCI) has been shown to be better able to detect abnormalities in lung function and it shows changes after treatment for one month. However, it is unclear how useful this technique is in detecting short-term changes following one inhalation. Hypertonic saline (salty sterile water) has been shown to improve mucus clearance, lung function and the LCI in patients with CF. This study assessed whether treatment with hypertonic saline improves ventilation differences within the lungs as measured by the Lung Clearance Index in patients with CF after a single inhalation.
Published Results