Safety, Efficacy and Pharmacokinetics of C21 in Subjects With IPF

Phase 2

Completed

• Conditions: Idiopathic Pulmonary Fibrosis
• Interventions: Drug: C21

• Registration Number: NCT04533022
• Lead Sponsor: Vicore Pharma AB

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-08-26
• Study First Submitted QC: 2020-08-26
• Study First Posted: 2020-08-31
• Study Start: 2020-11-13
• Primary Completion: 2024-03-30
• Study Completion: 2024-03-30
• Results First Submitted: 2025-03-24
• Status Verified: 2025-05
• Results First Submitted QC: 2025-05-08
• Last Update Submitted: 2025-05-08
• Results First Posted: 2025-05-23
• Last Update Posted: 2025-05-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 52

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
C21	C21	C21 100 mg BID (twice daily)

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events Occurring Over the Trial Period	Trial period of 36 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Tmax in a Sub-set of Subjects	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	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
AUClast in a Sub-set of Subjects	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	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
Accumulation Ratio AUC in a Sub-set of Subjects	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 was calculated in a subset of subjects after 0, 12, 24, and 36 weeks of dosing
Change From Baseline in Forced Vital Capacity (Non-imputed Data)	12, 24, and 36 weeks	Mean changes in forced vital capacity (FVC) (mL) from baseline to week 12, week 24, and week 36 were calculated
Change From Baseline in Forced Vital Capacity (Imputed Data)	12, 24, and 36 weeks	Mean changes in forced vital capacity (FVC) (mL) from baseline to week 12, week 24, and week 36 were calculated
Rate of Forced Vital Capacity Decline Over Time, FAS	12, 24, and 36 weeks	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.
Plasma Concentration of C21 Evaluated in a Sub-set of Subjects, Day 1	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	The plasma concentration of C21 (ng/mL) was calculated in a subset of subjects at specified timepoints post-dose.
Plasma Concentration of C21 Evaluated in a Sub-set of Subjects, Week 12	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	The plasma concentration of C21 (ng/mL) was calculated at specified timepoints post-dose after 12 weeks of dosing.
Plasma Concentration of C21 Evaluated in a Sub-set of Subjects, Week 24	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	The plasma concentration of C21 (ng/mL) was calculated at specified timepoints post-dose after 24 weeks of dosing.
Plasma Concentration of C21 Evaluated in a Sub-set of Subjects, Week 36	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	The plasma concentration of C21 (ng/mL) was calculated at specified timepoints post-dose after 36 weeks of dosing.
Cmax in a Sub-set of Subjects	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	The maximal plasma concentration (Cmax (ng/ml)) was calculated in a subset of subjects after 0, 12, 24, and 36 weeks of dosing

Trial Locations

Locations (21)

N. K. P. Salve Institute of Medical Sciences & Research Centre and Lata Mangeshkar Hospital; 🇮🇳 Nagpur, Maharashtra, India

Ace Hospital & Research Center; 🇮🇳 Pune, Maharashtra, India

Hindusthan Hospital; 🇮🇳 Coimbatore, Tamilnadu, India

Oyster & Pearl Hospitals; 🇮🇳 Pune, Maharashtra, India

Midland Healthcare and Research Centre; 🇮🇳 Lucknow, Uttar Pradesh, India

Grant Government Medical Collage and Sir J.J. Group of Hospitals; 🇮🇳 Mumbai, Maharashtra, India

Unity Hospital; 🇮🇳 Surat, Gujarat, India

Apollo Spectra Hospitals (Apollo Speciality Hospital Pvt. Ltd.); 🇮🇳 Kanpur, India

Clinical Hospital for Emergency Medical Care n.a. N.V. Solovyev; 🇷🇺 Yaroslavl, Russian Federation

University College London Hospitals; 🇬🇧 London, United Kingdom

Medicines Evaluation Unit; 🇬🇧 Manchester, United Kingdom

AMCMET Medical College and Sheth LG General Hospital; 🇮🇳 Ahmedabad, Gujarat, India

The Bhatia Hospital; 🇮🇳 Mumbai, Maharashtra, India

Jawaharlal Nehru Medical College - Aligarh Muslim University; 🇮🇳 Alīgarh, Uttar Pradesh, India

Odessa Regional Hospital; 🇺🇦 Odessa, Ukraine

Lviv National Medical University; 🇺🇦 Lviv, Ukraine

MNCE City Clinical Hospital; 🇺🇦 Kharkiv, Ukraine

University Hospital Birmingham; 🇬🇧 Birmingham, United Kingdom

University College Hospital; 🇬🇧 London, United Kingdom

Private Small Scale Enterprise Medical Center 'PULSE'; 🇺🇦 Vinnytsia, Ukraine

Royal Brompton Hospital; 🇬🇧 London, United Kingdom