Safety, Efficacy and Pharmacokinetics of C21 in Subjects With IPF

A Phase 2, Multi-Centre, Open-Label, Single-Arm Trial Investigating the Safety, Efficacy and Pharmacokinetics of C21 in Subjects With Idiopathic Pulmonary Fibrosis

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.

Study Overview

• Status: Completed
• Conditions: Idiopathic Pulmonary Fibrosis
• Intervention / Treatment: Drug: C21

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 2

Contacts and Locations

Study Locations

• India
  • Kanpur, India, 208001
    • Apollo Spectra Hospitals (Apollo Speciality Hospital Pvt. Ltd.)
  • Gujarat
    • Ahmedabad, Gujarat, India, 380008
      • AMCMET Medical College and Sheth LG General Hospital
    • Surat, Gujarat, India, 395010
      • Unity Hospital
  • Maharashtra
    • Mumbai, Maharashtra, India, 400007
      • The Bhatia Hospital
    • Mumbai, Maharashtra, India, 400008
      • Grant Government Medical Collage and Sir J.J. Group of Hospitals
    • Nagpur, Maharashtra, India, 440019
      • N. K. P. Salve Institute of Medical Sciences & Research Centre and Lata Mangeshkar Hospital
    • Pune, Maharashtra, India, 411004
      • ACE Hospital & Research Center
    • Pune, Maharashtra, India, 411005
      • Oyster & Pearl Hospitals
  • Tamilnadu
    • Coimbatore, Tamilnadu, India, 641028
      • Hindusthan Hospital
  • Uttar Pradesh
    • Alīgarh, Uttar Pradesh, India, 202002
      • Jawaharlal Nehru Medical College - Aligarh Muslim University
    • Lucknow, Uttar Pradesh, India
      • Midland Healthcare and Research Centre
• Russian Federation
  • Yaroslavl, Russian Federation
    • Clinical Hospital for Emergency Medical Care n.a. N.V. Solovyev
• Ukraine
  • Kharkiv, Ukraine, 61124
    • MNCE City Clinical Hospital
  • Lviv, Ukraine, 79010
    • Lviv National Medical University
  • Odessa, Ukraine, 65025
    • Odessa Regional Hospital
  • Vinnytsia, Ukraine, 21001
    • Private Small Scale Enterprise Medical Center 'PULSE'
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • University Hospital Birmingham
  • London, United Kingdom, SW3 6NP
    • Royal Brompton Hospital
  • London, United Kingdom
    • University College Hospital
  • London, United Kingdom
    • University College London Hospitals
  • Manchester, United Kingdom, M23 9QZ
    • Medicines Evaluation Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: C21; C21 100 mg BID (twice daily)	Drug: C21; C21 100 mg BID (twice daily); Other Names: Buloxibutid, Compound 21

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events Occurring Over the Trial Period	Number of participants with adverse events occurring over the trial period incl. number of participants with any TEAE, serious TEAEs, TEAEs leading to withdrawal from trial, TEAEs leading to discontinuation of treatment, treatment-related TEAEs leading to discontinuation of treatment, TEAEs leading to death, and serious treatment-related TEAEs. Adverse events were recorded from signing of informed consent until end of trial. Nature and frequency of adverse events are presented in details in the adverse events section.	Trial period of 36 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Forced Vital Capacity (Non-imputed Data)	Mean changes in forced vital capacity (FVC) (mL) from baseline to week 12, week 24, and week 36 were calculated	12, 24, and 36 weeks
Change From Baseline in Forced Vital Capacity (Imputed Data)	Mean changes in forced vital capacity (FVC) (mL) from baseline to week 12, week 24, and week 36 were calculated	12, 24, and 36 weeks
Rate of Forced Vital Capacity Decline Over Time, FAS	Model-based mean (90% CI) FVC changes over 12, 24, and 36 weeks were normalized to change over 24 weeks. A piece-wise linear regression model with knots at weeks 6 and 24 and unstructured covariance matrix was fitted to change from baseline data. Knot selection was performed by visual inspection. The model based change over 12, 24, and 36 weeks was normalized to represent a change over 24 weeks. Rate of decline was computed as y(t) - y(0) = t*Beta1 + max(0, t-6)*Beta2 + max(0,t-24)*Beta3, adjusted to show the decline per 24 weeks, where y is the value at the respective week and Beta is the model coefficient. No imputation of data was conducted.	12, 24, and 36 weeks
Plasma Concentration of C21 Evaluated in a Sub-set of Subjects, Day 1	The plasma concentration of C21 (ng/mL) was calculated in a subset of subjects at specified timepoints post-dose.	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
Plasma Concentration of C21 Evaluated in a Sub-set of Subjects, Week 12	The plasma concentration of C21 (ng/mL) was calculated at specified timepoints post-dose after 12 weeks of dosing.	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
Plasma Concentration of C21 Evaluated in a Sub-set of Subjects, Week 24	The plasma concentration of C21 (ng/mL) was calculated at specified timepoints post-dose after 24 weeks of dosing.	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
Plasma Concentration of C21 Evaluated in a Sub-set of Subjects, Week 36	The plasma concentration of C21 (ng/mL) was calculated at specified timepoints post-dose after 36 weeks of dosing.	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
Cmax in a Sub-set of Subjects	The maximal plasma concentration (Cmax (ng/ml)) was calculated in a subset of subjects after 0, 12, 24, and 36 weeks of dosing	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
Tmax in a Sub-set of Subjects	The time for the maximal plasma concentration (Tmax (h)) was calculated in a subset of subjects after 0, 12, 24, and 36 weeks of dosing	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
AUClast in a Sub-set of Subjects	Area under the plasma concentration time curve to the last quantified concentration (AUClast) (h*ng/mL) was calculated in a subset of subjects after 0, 12, 24, and 36 weeks of dosing	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
Accumulation Ratio AUC in a Sub-set of Subjects	Accumulation ratio AUC was calculated in a subset of subjects after 0, 12, 24, and 36 weeks of dosing	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

Collaborators and Investigators

• Sponsor: Vicore Pharma AB
• Collaborators: Orphan Reach Ltd.
• Investigators: Principal Investigator: Joanna Porter, MD, Respiratory Medicine, University College Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2020
• Primary Completion (Actual): March 30, 2024
• Study Completion (Actual): March 30, 2024

Study Registration Dates

• First Submitted: August 26, 2020
• First Submitted That Met QC Criteria: August 26, 2020
• First Posted (Actual): August 31, 2020

Study Record Updates

• Last Update Posted (Actual): May 23, 2025
• Last Update Submitted That Met QC Criteria: May 8, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Idiopathic Pulmonary Fibrosis
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Interstitial; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Fibrosis; Anti-Inflammatory Agents; Compound 21
• Other Study ID Numbers: VP-C21-005; 2020-000822-24 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No