Phase 2 Randomized, Double-Blind, Placebo-Controlled Study on the Efficacy and Safety of MBS2320 in Idiopathic Pulmonary Fibrosis Patients

Trial ID: 2023-504418-30-00
Protocol: IST-07
Sponsor: Modern Biosciences Limited

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Diseases & Conditions

Idiopathic pulmonary fibrosis

Objectives

The primary objective of this study is to evaluate the effect of daily oral dosing of **MBS2320** over 12 weeks compared with placebo in participants with **Idiopathic Pulmonary Fibrosis (IPF)** on the absolute change in forced vital capacity (FVC) measured in milliliters. This is clinically relevant as FVC is a critical parameter in assessing lung function and disease progression in IPF patients.

Secondary objectives include:

Evaluating the effect on % predicted FVC (%FVC) and % predicted diffusing capacity of lung for carbon monoxide (%DLCO).
Understanding any differential treatment effect between two strata based on the concomitant use of an approved anti-fibrotic drug at randomization.
Assessing the impact on variables such as acute exacerbations, carbon monoxide transfer coefficient (KCO), alveolar volume (AV), and respiratory adverse events (AEs).
Evaluating changes in forced expiratory volume in 1 second (FEV1), FEV1/FVC ratio, cough, dyspnea, and quality of life measures including the 36-Item Short Form Health Survey (SF-36), King’s Brief Interstitial Lung Disease (KBILD), and Living with Pulmonary Fibrosis questionnaire (L-PF).
Assessing the decline or increase in %FVC and absolute FVC, as well as performance in the 6-minute walking test (6MWT).
Evaluating the effect on disease progression.

Participants

The clinical trial involves a total of **150 participants** diagnosed with **Idiopathic Pulmonary Fibrosis** (IPF). The study population includes both male and female subjects aged 40 years and older. Participants were selected based on specific criteria, including a confirmed diagnosis of IPF according to established guidelines, a forced vital capacity (FVC) of at least 45% of the predicted value, and a diffusing capacity of the lungs for carbon monoxide (DLCO) corrected for hemoglobin between 25% and 80% of the predicted value. Additionally, participants must have a minimum distance of 150 meters on the 6-minute walk test (6MWT) and a FEV1/FVC ratio greater than 0.70. Those on anti-fibrotic treatments such as nintedanib or pirfenidone must be on a stable dose for at least 8 weeks prior to the study. The trial includes individuals who are capable of providing informed consent and are expected to comply with the study protocol. Participants' lifestyle considerations, such as the use of contraception, are in accordance with local regulations. The trial does not include any specific dietary or physical activity requirements beyond those related to the management of IPF.

Plans and Procedures

The clinical trial is designed as a **randomized, double-blind, placebo-controlled, Phase 2 study** to evaluate the efficacy and safety of MBS2320 in patients diagnosed with **Idiopathic Pulmonary Fibrosis (IPF)**. The primary objective is to assess the effect of daily oral dosing of MBS2320 over a 12-week period compared to placebo, focusing on the absolute change in forced vital capacity (FVC) in milliliters. The trial is expected to commence recruitment on October 2, 2023, and conclude by November 1, 2024.

Participants will be involved in the study for a total duration of 12 weeks, with the possibility of early termination if specific conditions arise, such as significant adverse events or non-compliance with the study protocol. The study includes several key visits: an initial screening visit to confirm eligibility based on criteria such as age, diagnosis, and lung function parameters; regular follow-up visits at weeks 4, 8, and 12 to monitor changes in FVC, DLCO, and other secondary endpoints; and an end-of-study visit to assess overall outcomes and safety.

Inclusion criteria require participants to be 40 years or older, have a confirmed diagnosis of IPF, and meet specific lung function thresholds. Exclusion criteria are not explicitly detailed in the provided data. The study will utilize a placebo that matches MBS2320 capsules, with both the active drug and placebo administered orally. The trial's primary endpoint is the change from baseline in FVC up to week 12, while secondary endpoints include changes in %FVC, %DLCO, and other respiratory parameters, as well as the time to first acute exacerbation.

Treatment

The clinical trial involves the administration of **MBS2320**, an investigational medication, to evaluate its efficacy and safety in patients with **Idiopathic Pulmonary Fibrosis (IPF)**. **MBS2320** is provided in the form of a capsule, with each capsule containing 40 mg of the active substance. The medication is of chemical origin and is manufactured by Modern Biosciences PLC. Participants in the trial will receive a daily oral dose of 40 mg of **MBS2320** for a maximum treatment period of 12 weeks. The administration route is oral, and the dosing schedule is designed to ensure consistent daily intake. Compliance with the dosing regimen will be monitored throughout the study to ensure adherence to the protocol.

In addition to the experimental treatment, a **placebo** is used as a comparator in this double-blind, placebo-controlled study. The placebo is designed to match the **MBS2320** capsules in appearance and is also administered orally at a dosage of 40 mg daily. The placebo serves as a control to assess the true efficacy of **MBS2320** by comparing outcomes between the treatment and placebo groups. The use of a placebo is critical in maintaining the study's blinding and ensuring unbiased results. Participants' adherence to the placebo regimen will be monitored similarly to those receiving the active treatment.

Efficacy

The efficacy of MBS2320 in patients with **Idiopathic Pulmonary Fibrosis (IPF)** will be assessed through a randomized, double-blind, placebo-controlled, Phase 2 clinical trial. The primary endpoint for evaluating efficacy is the change from baseline in forced vital capacity (FVC) compared to placebo, measured up to Week 12 or until the point of discontinuation. Secondary endpoints include changes from baseline in percentage predicted FVC (%FVC) and percentage predicted diffusing capacity of the lungs for carbon monoxide (%DLCO) up to Week 12. Additional secondary endpoints involve the time to first acute exacerbation, changes in FEV and FEV/FVC ratio at Weeks 4, 8, and 12, and changes in patient-reported outcomes such as SF-36, KBKILD, and L-PF at the same timepoints. The proportion of participants with evidence of disease progression, defined as a decline in %FVC of 10% or more, a decline in %DLCO of 15% or more, lung transplantation, or death, will also be evaluated.

Measurements will be collected at specified intervals throughout the 12-week treatment period. The trial will utilize validated scales and laboratory tests to ensure accurate and reliable data collection. The analysis will focus on comparing the changes in these parameters between the MBS2320 and placebo groups to determine the efficacy of the treatment. The study aims to provide comprehensive data on the impact of MBS2320 on lung function and overall health status in patients with IPF.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Participant must be 40 years or older at the time of signing the informed consent.
Diagnosis of IPF based on: a. ATS/ERS/JRS/ALAT guidelines (Raghu, 2022) as confirmed by the investigator based on chest high-resolution computed tomography (hrCT) scan taken within
Has an FVC ≥45% of predicted.
Has a DLCO corrected for hemoglobin ≥25% and ≤80% of predicted.
Minimum distance on 6MWT of 150 meters.
Has a FEV1/FVC ratio >0.70.
If on anti-fibrotics, only the approved treatments of nintedanib or pirfenidone are allowed. Participants must be on a stable dose for at least 8 weeks prior to Visit 1 and during Screening and are predicted to remain stable during the course of the study. A combination of both pirfenidone plus nintedanib is not allowed. Where approved, patients not currently receiving treatment with pirfenidone or nintedanib therapy should have a valid reason: this includes contraindication to therapy (including concerns around DDI), previous treatment discontinued due to lack of response or tolerability, not meeting national or regional eligibility criteria for anti-fibrotic treatment, or patient choice.
Male and female participants using contraception in line with local regulations regarding the methods of contraception for those participating in clinical studies (Appendix 4).
Capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Has a life expectancy of at least 12 months (in the opinion of the investigator).
According to the investigator’s best judgment, can comply with the requirements of the protocol

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Exclusion Criteria

Emphysema ≥50% on hrCT or the extent of emphysema is greater than the extent of fibrosis according to the central reviewer’s assessment from the most recent hrCT or if reported by the local reviewer.
Active infection that is clinically significant in the Investigator’s opinion, or any infection requiring hospitalization or treatment with intravenous antimicrobials ≤60 days of screening, or any infection requiring oral antimicrobial therapy ≤2 weeks of the baseline visit.
Screening laboratory values meeting the following criteria: • Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >1.5 ×ULN or total bilirubin >1.5 × ULN; • Estimated glomerular filtration rate by simplified 4-variable Modification of Diet in Renal Disease formula ≤60 mL/min/1.73 m²; • Total white blood cell count <3,000/µL; • Absolute neutrophil count <1,500/µL; • Platelet count <100,000/µL; • Absolute lymphocyte count <800/µL; • Hemoglobin <9 gm/dL. • Serum bicarbonate ≤20 mmol/L or ≥29 mmol/L. Note: One repeat assessment of any screening laboratory test is acceptable as long as, in the Investigator’s opinion, this does not constitute a risk when taking the study medication and would not interfere with the study objectives.
Any clinically significant neurological, GI, renal, hepatic, cardiovascular, psychiatric, respiratory, metabolic, endocrine, hematological, ophthalmic, or other major disorder which, in the opinion of the Investigator, would put the participant at risk by participating in the study (except for IPF or disorders associated with IPF that, in the Investigator’s opinion, do not constitute a risk when taking the study treatments and would not interfere with the study objectives).
Have experienced clinically significant metabolic acidosis in the past.
Is receiving systemic corticosteroids equivalent to prednisone >10 mg/day or equivalent within 2 weeks of baseline.
Received azathioprine, cyclophosphamide, or cyclosporine A within 4 weeks of baseline.
Baseline resting oxygen saturation is <89% on room air or supplemental oxygen up to a maximum of 4 L/min.
Unable to refrain from use of the following: • Short acting bronchodilators (e.g., salbutamol/albuterol, ipratropium) on the day of and within 8 hours of pulmonary function tests (PFTs), DLCO, and 6MWTassessments. • Long-acting bronchodilators with twice daily administration (e.g., salmeterol, formoterol, aclidinium) on the day of and within 12 hours of PFTs, DLCO, and 6MWT assessments. • Ultra-long-acting bronchodilators with once daily administration (e.g., tiotropium, vilanterol) on the day of and within 24 hours of PFTs, DLCO, and 6MWT assessments.
Has a known post bronchodilator (short acting beta agonist [SABA] – albuterol or salbutamol) increase in FEV1 of >10% and in FVC of >7.5%
Use of strong CYP3A4 inhibitors/inducers within 30 days or 5 half-lives, whichever is longer, prior to baseline visit. See Appendix 6 for a full list of strong CYP3A4 inhibitors/inducers that are prohibited for concomitant use.
Any current malignancy or a history of malignancy within the previous 5 years prior to screening, with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ.
Use of uridine 5’-diphospho-glucuronosyltransferase (UGT)2B7 inhibitors within 30 days or 5 half-lives, whichever is longer, prior to baseline visit. See Appendix 6 for a full list of UGT2B7 inhibitors that are prohibited for concomitant use.
Systemically administered CA inhibitors within 30 days or 5 half-lives, whichever is longer, prior to baseline visit. See Appendix 6 for a full list of CA inhibitors that are prohibited for concomitant use.
A live virus vaccination within the 90 days prior to the baseline visit (1 year for Bacillus Calmette-Guerin vaccination) or intent to receive a live virus vaccination during the study or within 28 days after study completion
Participation in another clinical study (including attending follow-up visits) or receipt of any investigational drug within a minimum of 90 days or 5 half-lives of the drug (whichever is longer) prior to the baseline visit.
Previously received MBS2320.
Current use of tobacco products and/or vaping.
Donated blood in the 90 days prior to screening.
Prior GI surgeries or any GI procedures/conditions that may cause concerns with absorption of the study drug.
History of major surgery (requiring regional block or general anesthesia) within 3 months prior to screening or planned major surgery during the study.
Male participants who have not undergone a vasectomy and do not agree to use appropriate contraception (i.e., a condom with spermicidal foam/gel/film/cream/suppository) with their partners of childbearing potential or partners sterilized by tubal ligation, or who do not agree to use an additional highly effective method of contraception with their partners of childbearing potential.
Abnormality in heart rate, blood pressure or 12-lead ECG at screening that in the opinion of the Investigator increases the risk of participating in the study. Specific 12-lead ECG exclusion criteria are participants with QT corrected using Fridericia’s formula (QTcF) of >450 ms (males) or >460 ms (females) and participants with PR interval of >220 ms at screening (1 repeat assessment is allowed).
Male participants who do not agree to refrain from donating sperm from the time of the first dose until 90 days after the final dosing occasion.
Female participants of childbearing potential who do not agree to use a highly effective method of birth control (i.e., contraceptive measure with a failure rate of <1% per year) in conjunction with male contraception (i.e., a condom with spermicidal foam/gel/film/cream/suppository) from the time of the first dose until 90 days after the final dosing occasion.
Participants who are breastfeeding or lactating.
Risk factors for severe COVID-19, which in the opinion of the Investigator would put the participant at risk by participating in the study
Significant history of drug allergy, including to MBS2320 or excipients, as determined by the Investigator.
Allergic reaction, anaphylaxis, or other reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis or leukopenia) to sulfonamide drugs.
A significant history of alcoholism or drug/chemical abuse within 1 year prior to screening, as determined by the investigator.
History of opportunistic, chronic, or recurrent infections including untreated latent tuberculosis.
Participants with chronic obstructive pulmonary disease (COPD) or asthma that: • require >2 maintenance therapies • have experienced an exacerbation requiring hospitalization or systemic corticosteroids within 12 months prior to screening. Patients with COPD that have had an exacerbation treated with antibiotics are also excluded.
Are uncontrolled in the opinion of the investigator.Positive serology results for hepatitis B surface antigen (HbsAg) or hepatitis B core antibody (HbcAb), hepatitis C (HCV) antibody with positive confirmatory test for HCV (e.g., polymerase chain reaction [PCR]), or human immunodeficiency virus (HIV) antibody at the screening visit. Note: Participants with a positive HbcAb and a negative HbsAg can be included in this the study if HbsAb is positive (considered immune after a natural infection). Participants with negative confirmatory test for HCV can be included in this clinical study.
Participants who are committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.
Applicable in France only: a. persons deprived of their liberty by judicial or administrative decision b. persons under psychiatric care without their consent (as per Articles L.3212-1, L.3213-1 and L.1121-8) c. persons admitted to a health or social institution for purposes other than research d. adults subject to a legal protection measure (guardianship, curatorship, etc.) e. persons unable to give their consent f. persons who are not affiliated to a social security scheme or who are beneficiaries of such a scheme.

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
France	Not Recruiting	02 Oct 2023	45
Germany	Not Recruiting	02 Oct 2023	47
Greece	Not Recruiting	02 Oct 2023	24
Hungary	Not Recruiting	02 Oct 2023	17
Italy	Not Recruiting	02 Oct 2023	15
Spain	Not Recruiting	02 Oct 2023	8