Efficacy, Safety and Tolerability of NP-120 on Idiopathic Pulmonary Fibrosis and Its Associated Cough

• ClinicalTrials.gov Identifier: NCT04318704
• Recruitment Status: Recruiting
• First Posted: March 24, 2020
• Last Update Posted: December 10, 2020
• Sponsor: Algernon Pharmaceuticals
• Information provided by (Responsible Party): Algernon Pharmaceuticals

Study Description

Brief Summary:

NP-120 (Ifenprodil) has been shown to mediate anti-inflammatory responses and reduce pulmonary fibrosis in a murine model of Idiopathic Pulmonary Fibrosis (IPF). In addition, NP-120 significantly reduced both cough frequency and onset in a guinea pig tussive model. The purpose of this proof-of-concept trial is to determine the efficacy of NP-120 in the treatment of IPF and its associated cough.

Condition or disease	Intervention/treatment	Phase
Idiopathic Pulmonary Fibrosis	Drug: Ifenprodil	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label Study of the Efficacy, Safety and Tolerability of NP-120 on Idiopathic Pulmonary Fibrosis and Its Associated Cough
• Actual Study Start Date: July 29, 2020
• Estimated Primary Completion Date: March 2021
• Estimated Study Completion Date: June 2021

Arms and Interventions

Arm	Intervention/treatment
Single Arm Active; Ifenprodil	Drug: Ifenprodil; Ifenprodil 20 mg TID

Outcome Measures

Primary Outcome Measures :

1. A ≥50% reduction in the average number of coughs per hour over 24 hours comparing baseline to treatment period using an ambulatory cough monitor [ Time Frame: Baseline and week 12 (≥11 weeks of treatment) ]
2. No worsening of force vital capacity (FVC) in either mL or % predicted [ Time Frame: Baseline and week 12 (≥11 weeks of treatment) ]

Eligibility Criteria

• Ages Eligible for Study: up to 85 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Male and female subjects with a diagnosis of IPF established during the previous seven years according to ATS/ERS/Fleischner criteria.
2. Score ≥ 40 mm on the Cough Severity VAS at Screening

3. Lung function parameters as follows:

   1. Forced Vital Capacity (FVC) ≥ 45% of the predicted value at screening.
   2. Diffusion lung capacity for carbon monoxide (DLCO) (corrected for Hb) of 30% to 79% of the predicted value at screening.
4. Any existing Standard of Care (SoC) treatment (e.g. pirfenidone or nintedanib) must be deemed as stable (minimum three months) before enrollment.
5. Subjects must sign and date a written, informed consent form and any required authorization prior to initiation of any study procedures.

Exclusion Criteria:

1. Currently has significant airways obstruction: Forced Expiratory Volume in 1 s (FEV1)/Forced Vital Capacity (FVC) ratio of < 0.7 at screening.
2. Has clinical evidence of active infection, including, but not limited to, bronchitis, pneumonia, sinusitis, urinary tract infection, and cellulitis.
3. Has a history of malignancy within the last 2 years with the exception of basal cell carcinoma, chronic lymphocytic leukaemia (under observation) and prostate cancer requiring anti-androgens, localised treatment (minor surgery, radiotherapy) and/or managed by observation, and squamous cell carcinoma if diagnosed and successfully treated more than 6 months prior to the study. SCC diagnosed with the past 6 months will be exclusionary.
4. Patients experiencing cerebral hemorrhage or cerebral infarction at screening/baseline.
5. Has any condition other than IPF that, in the opinion of the investigator, is likely to result in the death of the subject within the next 2 years.
6. Presence of other disease that may interfere with testing procedures or in the judgement of the Investigator may interfere with trial participation or may put the patient at risk when participating in this trial.
7. Is likely to receive lung transplantation within the next 12 months.
8. Currently receiving high dose corticosteroid, cytotoxic (e.g., chlorambucil, azathioprine, cyclophosphamide, methotrexate), vasodilator therapy for pulmonary hypertension (e.g., bosentan), and or investigational therapy for idiopathic pulmonary fibrosis (IPF) or administration of such therapeutics within 4 weeks of initial screening (or 5 half-lives, whichever is longer). A current dose of less than or equal to 15 mg/day of prednisone or its equivalent is acceptable if the dose is anticipated to remain stable during the study.

9. Has a history of unstable or deteriorating cardiac or pulmonary disease (other than IPF) within the previous six months, including, but not limited to, the following:

   1. Unstable angina pectoris or myocardial infarction, or percutaneous coronary intervention within the last 6 months,
   2. Congestive heart failure requiring hospitalization,
   3. Uncontrolled clinically significant arrhythmias.
10. If female, the subject is pregnant or lactating or intending to become pregnant before participating in this study during the study and within (5 half- lives plus 30 days) after last dose of the study drug; or intending to donate ova during such time period.
11. Women considered to be of childbearing potential who do not use highly effective birth control methods during the study.
12. Known or suspected allergy to the trial drug or the relevant drugs given in the trial.
13. Involvement in a clinical research study within 4 weeks prior to screening and/or prior enrollment in the study. Participation in registry studies is permitted.

Contacts and Locations

Contacts

Contact: Nancy Stewart, Ph.D.; 204-928-7905; nstewart@gvicds.com

Locations

Australia, New South Wales

Vale Medical Practice; Recruiting

Brookvale, New South Wales, Australia

Contact: Naomi DeFazio 61298556000 NDeFazio@sonicclinicaltrials.com

Concord Repatriation General Hospital; Recruiting

Concord, New South Wales, Australia

Contact: Elizabeth Vietch 61297675000 elizabeth.veich@health.nsw.gov.au

Contact: Kerrie Wade 61297676334 kerrie.wade@health.nsw.gov.au

Australia, Queensland

Cairns Hospital; Recruiting

Cairns, Queensland, Australia

Contact: Clinical Research Unit 61742268085 CairnsCRU@health.qld.gov.au

New Zealand

The University of Otago; Recruiting

Christchurch, Canterbury, New Zealand

Contact: Lutz Beckert 0064033640640 Lutz.Beckert@cdhb.health.nz

Contact: Liz Cousins 03364640 liz.cousins@otago.ac.nz

Waikato Hospital; Recruiting

Hamilton, Waikato, New Zealand

Contact: Catherina Chang (64) 078398899 cat.chang@waikatodhb.health.nz

Contact: Christine Tuffery 964) 21759531 christine.tuffery@waikatodhb.health.nz

Sponsors and Collaborators

Algernon Pharmaceuticals

More Information

• Responsible Party: Algernon Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04318704
• Other Study ID Numbers: AGN120-1
• First Posted: March 24, 2020
• Last Update Posted: December 10, 2020
• Last Verified: December 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Algernon Pharmaceuticals:

Cough

Additional relevant MeSH terms:

Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Fibrosis; Lung Diseases; Idiopathic Interstitial Pneumonias; Lung Diseases, Interstitial; Pathologic Processes; Respiratory Tract Diseases; Ifenprodil; Adrenergic alpha-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Vasodilator Agents; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents