C21 in IPF
Research type
Research Study
Full 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
IRAS ID
282448
Contact name
Joanna Porter
Contact email
Sponsor organisation
Vicore Pharma AB
Eudract number
2020-000822-24
Duration of Study in the UK
2 years, 4 months, 1 days
Research summary
Research Summary
A Phase 2, Multi-Centre, Open-Label, Single-Arm Trial Investigating the Safety, Efficacy and Pharmacokinetics of C21 in Subjects with Idiopathic Pulmonary Fibrosis.
Primary Objective to investigate the safety of C21 200 mg daily dose (100 mg b.i.d.) administered orally to subjects with IPF.
Secondary Objectives to evaluate:
• The efficacy of C21 200 mg daily dose (100 mg b.i.d.) administered orally to subjects with IPF for 24 weeks
• The efficacy of C21 200 mg daily dose (100 mg b.i.d.) administered orally to subjects with IPF for 36 weeks
• The pharmacokinetic (PK) profile of C21 200 mg daily dose (100 mg b.i.d.) after multiple dosingExploratory Objectives: To investigate a range of laboratory parameters as potential biomarkers of inflammation, proliferation and fibrosis following oral administration of C21 200 mg daily dose (100 mg b.i.d.).
This is an multi-centre, open-label, single-arm trial investigating the safety and efficacy of C21 in which subjects with IPF will be treated for a maximum of 36 weeks. In total, approximately 60 subjects will be recruited at trial sites in Europe. To ensure careful and ongoing evaluation of the individual risk/benefit profiles, each subject will undergo a medical evaluation by the investigator at the end of every 12-week treatment period, where the investigator will evaluate if continuation into the next 12-week treatment period is considered safe for the individual subject.
Eligibility criteria: Diagnosis of IPF within 3 years prior to visit 1, age ≥40 years, FVC ≥80% predicted at visit 1, FEV1/FVC ratio ≥0.7 prebonchodilator at visit 1,oxygen saturation (Sp02) >85% by pulse oximetry while breathing ambient air at rest at visit 1, diffuse capacity for carbon monoxide >30%, High resolution computed tomography within 36 months prior to visit 1.Summary of Results
Subject Disposition and Demography
A total of 138 people were screened for the trial, out of which 52 received the study treatment. Among these 52 participants, 27 (51.9%) completed the 36-week study. However, 25 participants (48.1%) withdrew early. The reasons for withdrawal included 15 people who withdrew their consent, 7 who discontinued due to adverse events (2 were fatal), and 3 who experienced a decline in lung function.
Demographics
The majority of the participants were male, accounting for 78% of the total. The average age of the participants was 67.5 years. Their average height was 161.73 cm, and their average weight was 65.02 kg. The average Body Mass Index (BMI) was 24.70. Most participants were from India, making up 72% of the group, and the majority were of Asian race (72%), followed by White race (28%).
Baseline Disease Characteristics
On average, participants had been diagnosed with IPF (Idiopathic Pulmonary Fibrosis) for 1.04 years. The average Forced Vital Capacity (FVC), which measures lung capacity, was 2.3865 liters, and the percentage of predicted FVC (FVCpp) was 75.22%. The average Forced Expiratory Volume in 1 second (FEV1) was 1.9153 liters, which is 77.45% of the predicted normal value. The average oxygen saturation at screening was 95.2%. According to HRCT (High-Resolution Computed Tomography) scans, 38% of subjects had a typical UIP (usual interstitial pneumonia) pattern, while 62% had a probable UIP pattern.
Conclusions
Efficacy
The study observed stabilization or improvement in lung function over the 36 weeks of C21 treatment. The mean change in FVC from baseline to week 36 was 9.4 mL with imputed data and 216 mL with non-imputed data. Subgroup analysis indicated larger increases in FVC in patients with probable UIP compared to those with typical UIP, and in patients from India compared to those from other regions.
Pharmacokinetics (PK)
The drug C21, administered at 100 mg twice daily, showed that the peak concentration (Cmax) and the area under the curve (AUClast) were highest on the first day of dosing and decreased over the following weeks. There was no accumulation of the drug over the 36 weeks of dosing.
Safety
C21 was well tolerated at a dose of 100 mg twice daily for 36 weeks in subjects with IPF. Out of 148 reported adverse events, 17 were related to the drug and were observed in 10 subjects (19.2%). Most adverse events were mild or moderate in severity. No serious adverse events were considered related to the treatment. There were two fatal adverse events (COVID-19 and complications from other conditions), but these were not related to the trial treatment. The most frequently reported side effect was hair loss (alopecia), which was mild to moderate and reversible.
REC name
East Midlands - Leicester South Research Ethics Committee
REC reference
20/EM/0138
Date of REC Opinion
6 Jul 2020
REC opinion
Further Information Favourable Opinion