Clinical trial NCT04533022: Safety, Efficacy and Pharmacokinetics of C21 in Subjects With IPF
Official title: A Phase 2, Multi-Centre, Open-Label, Single-Arm Trial Investigating the Safety, Efficacy and Pharmacokinetics of C21 in Subjects With Idiopathic Pulmonary Fibrosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Idiopathic Pulmonary Fibrosis
Keywords: Idiopathic Pulmonary Fibrosis
Lead sponsor: Vicore Pharma AB
Sponsor class: INDUSTRY
Collaborators: name: Orphan Reach Ltd.
First posted: 2020-08-31
Enrollment: 52
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This trial is a multi-centre, open-label, single-arm phase 2 trial investigating the safety, efficacy and pharmacokinetics of C21 in subjects with idiopathic pulmonary fibrosis.


Eligibility criteria: Inclusion Criteria:

1. Written informed consent, consistent with ICH-GCP R2 and local laws, obtained before the initiation of any trial related procedure
2. A diagnosis of IPF within 5 years prior to Visit 1, as per either ATS/ERS/JRS/ATLAT/Fleischner guidelines
3. Age ≥40 years
4. Forced vital capacity (FVC) ≥60% predicted at Visit 1 (specifically for UK: FVC ≥80% predicted at Visit 1)
5. Forced expiratory volume in the first sec (FEV1)/FVC ratio ≥0.7 prebronchodilator at Visit 1
6. Oxygen saturation (SpO2) \>85% by pulse oximetry while breathing ambient air at rest at Visit 1
7. High-resolution computed tomography (HRCT) within 36 months prior to Visit 1 with central reading demonstrating either a or b, and c:

   a. A pattern consistent with usual interstitial pneumonitis (UIP) according to ATS/ERS/JRS/ALAT or Fleischner guidelines i. UIP ii. Probable UIP or b. A pattern indeterminate for UIP according to either ATS/ERS/JRS/ALAT or Fleischner guidelines and a historical biopsy consistent with IPF c. Extent of fibrosis \> extent of emphysema
8. Fully vaccinated against COVID-19 prior to screening (Visit 1). Subjects are considered fully vaccinated for COVID-19 ≥14 days after they have received vaccination dose(s) according to local label

Exclusion Criteria:

1. Previous use of antifibrotic treatment for an interstitial lung disease (e.g. nintedanib or pirfenidone) for \> 6 months
2. Smoking (including e-cigarettes) within 6 months prior to Visit 1
3. Body mass index (BMI) \>35 or \<18
4. IPF exacerbation within 3 months prior to Visit 1:

   * Acute worsening or development of dyspnoea typically \<1 month duration
   * Computed tomography with new bilateral ground-glass opacity and/or consolidation superimposed on a background pattern consistent with usual interstitial pneumonia pattern (if no previous computed tomography is available, the qualifier "new" can be dropped)
   * Deterioration not fully explained by cardiac failure or fluid overload
5. Concurrent serious medical condition with special attention to cardiac or ophthalmic conditions (e.g. contraindications to cataract surgery) which in the opinion of the investigator makes the subject inappropriate for this trial
6. Malignancy within the past 5 years with the exception of in situ removal of basal cell carcinoma and cervical intraepithelial neoplasia grade I
7. Treatment with any of the medications listed below within 4 weeks prior to Visit 1:

   * Cytochrome p450 (CYP) 3A4 inducers (e.g. rifampicin, phenytoin, St. John's Wort)
   * CYP3A4 inhibitors (e.g. clarithromycin, ketoconazole, nefazodone, itraconazole, ritonavir)
   * Medicines that are substrates of CYP1A2, CYP3A4 or CYP2C9 with a narrow therapeutic range
   * Experimental drugs
   * Any systemic immunosuppressive therapies other than:
   * Inhaled corticosteroids which can be used throughout the trial period provided the dose is kept stable
   * Corticosteroids for the treatment of acute exacerbations
   * The continuation of stable doses of ≤15 mg daily doses of prednisolone
8. Treatment with any of the medications listed below within 2 weeks prior to Visit 1:

   * Proton pump inhibitors (PPI's) more than once daily
   * Histamine H2 receptor antagonists (H2RA's)
   * Sulphasalazine and rosuvastatin
   * High dose breast cancer resistance protein sensitive substrates (other than sulphasalazine or rosuvastatin)
9. Any of the following findings at Visit 1:

   * Prolonged QTcF (QT interval with Fridericia's correction) (\>450 ms), cardiac arrhythmias or any clinically significant abnormalities in the resting ECG, as judged by the Investigator
   * Positive results for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCVAb) or human immunodeficiency virus 1+2 antigen/antibody (HIV 1+2 Ag/Ab)
   * Positive serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin)
10. Inability to generate lung function data at Visit 1 meeting the minimum standards of the ATS/ERS 2005 guideline, as determined by central review
11. Clinically significant abnormal laboratory value at Visit 1 indicating a potential risk for the subject if enrolled in the trial as evaluated by the investigator
12. Pregnant or breast-feeding female subjects
13. Female subjects of childbearing potential not willing to use contraceptive methods
14. Male subjects not willing to use contraceptive methods
15. Subjects not willing to adhere to dietary restrictions during the trial period
16. Participation in any other interventional trial during the trial period
17. Subjects known or suspected of not being able to comply with this trial protocol (e.g. due to alcoholism, drug dependency or psychological disorder)
18. Discontinuation or change of previous antifibrotic treatment (e.g. nintedanib or pirfenidone) due to disease progression

Primary outcomes:
measure: Number of Participants With Adverse Events Occurring Over the Trial Period
timeFrame: Trial period of 36 weeks
Secondary outcomes:
measure: Change From Baseline in Forced Vital Capacity (Non-imputed Data)
timeFrame: 12, 24, and 36 weeks
measure: Change From Baseline in Forced Vital Capacity (Imputed Data)
timeFrame: 12, 24, and 36 weeks
measure: Rate of Forced Vital Capacity Decline Over Time, FAS
timeFrame: 12, 24, and 36 weeks
measure: Plasma Concentration of C21 Evaluated in a Sub-set of Subjects, Day 1
timeFrame: Prior to dosing, 30 min post dose, 1 h post dose, 2 h post dose, 3 h post dose, and 4 h post dose on Day 1
measure: Plasma Concentration of C21 Evaluated in a Sub-set of Subjects, Week 12
timeFrame: Prior to dosing, 30 min post dose, 1 h post dose, 2 h post dose, 3 h post dose, and 4 h post dose at Week 12
measure: Plasma Concentration of C21 Evaluated in a Sub-set of Subjects, Week 24
timeFrame: Prior to dosing, 30 min post dose, 1 h post dose, 2 h post dose, 3 h post dose, and 4 h post dose at Week 24
measure: Plasma Concentration of C21 Evaluated in a Sub-set of Subjects, Week 36
timeFrame: Prior to dosing, 30 min post dose, 1 h post dose, 2 h post dose, 3 h post dose, and 4 h post dose at Week 36
measure: Cmax in a Sub-set of Subjects
timeFrame: Prior to dosing, 30 min post dose, 1 h post dose, 2 h post dose, 3 h post dose, and 4 h post dose at Weeks 0, 12, 24, and 36
measure: Tmax in a Sub-set of Subjects
timeFrame: Prior to dosing, 30 min post dose, 1 h post dose, 2 h post dose, 3 h post dose, and 4 h post dose at Weeks 0, 12, 24, and 36
measure: AUClast in a Sub-set of Subjects
timeFrame: Prior to dosing, 30 min post dose, 1 h post dose, 2 h post dose, 3 h post dose, and 4 h post dose at Weeks 0, 12, 24, and 36
measure: Accumulation Ratio AUC in a Sub-set of Subjects
timeFrame: Prior to dosing, 30 min post dose, 1 h post dose, 2 h post dose, 3 h post dose, and 4 h post dose at Weeks 0, 12, 24, and 36
Other outcomes:
Locations:
city: Ahmedabad
country: India
facility: AMCMET Medical College and Sheth LG General Hospital
state: Gujarat
city: Surat
country: India
facility: Unity Hospital
state: Gujarat
city: Mumbai
country: India
facility: The Bhatia Hospital
state: Maharashtra
city: Mumbai
country: India
facility: Grant Government Medical Collage and Sir J.J. Group of Hospitals
state: Maharashtra
city: Nagpur
country: India
facility: N. K. P. Salve Institute of Medical Sciences & Research Centre and Lata Mangeshkar Hospital
state: Maharashtra
city: Pune
country: India
facility: Ace Hospital & Research Center
state: Maharashtra
city: Pune
country: India
facility: Oyster & Pearl Hospitals
state: Maharashtra
city: Coimbatore
country: India
facility: Hindusthan Hospital
state: Tamilnadu
city: Alīgarh
country: India
facility: Jawaharlal Nehru Medical College - Aligarh Muslim University
state: Uttar Pradesh
city: Lucknow
country: India
facility: Midland Healthcare and Research Centre
state: Uttar Pradesh
city: Kanpur
country: India
facility: Apollo Spectra Hospitals (Apollo Speciality Hospital Pvt. Ltd.)
city: Yaroslavl
country: Russian Federation
facility: Clinical Hospital for Emergency Medical Care n.a. N.V. Solovyev
city: Kharkiv
country: Ukraine
facility: MNCE City Clinical Hospital
city: Lviv
country: Ukraine
facility: Lviv National Medical University
city: Odessa
country: Ukraine
facility: Odessa Regional Hospital
city: Vinnytsia
country: Ukraine
facility: Private Small Scale Enterprise Medical Center 'PULSE'
city: Birmingham
country: United Kingdom
facility: University Hospital Birmingham
city: London
country: United Kingdom
facility: Royal Brompton Hospital
city: London
country: United Kingdom
facility: University College Hospital
city: London
country: United Kingdom
facility: University College London Hospitals
city: Manchester
country: United Kingdom
facility: Medicines Evaluation Unit
Study officials:
affiliation: Respiratory Medicine, University College Hospital
name: Joanna Porter, MD
role: PRINCIPAL_INVESTIGATOR
References: