A Study to Investigate MBS2320 Patients with IPF

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Modern Biosciences Limited, Modern Biosciences Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01], Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

24 Oct 2023 → 14 Mar 2024

Decision date (initial)

2023-09-26

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Modern Biosciences Ltd.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the effect of daily oral dosing of MBS2320 over 12 weeks compared with placebo in participants with IPF on absolute change in forced vital capacity (FVC) (mL)

Secondary objectives 6

1. To evaluate the effect of daily oral dosing of MBS2320 over 12 weeks compared with placebo in participants with IPF on % predicted FVC (%FVC)
2. To evaluate the effect of daily oral dosing of MBS2320 over 12 weeks compared with placebo in participants with IPF on % predicted diffusing capacity of lung for carbon monoxide (%DLCO)
3. To understand any differential treatment effect of daily oral dosing of MBS2320 over 12 weeks compared with placebo in participants with IPF between the two strata (concomitant use of an approved anti-fibrotic drug [nintedanib or pirfenidone] at randomization versus no concomitant use of an approved anti-fibrotic drug at randomization) on the primary and secondary endpoints.
4. To evaluate the effect of daily oral dosing of MBS2320 over 12 weeks compared with placebo in participants with IPF on the following variables: Acute exacerbations, Carbon monoxide transfer coefficient (KCO), Alveolar volume (AV), Respiratory AEs
5. To evaluate the effect of daily oral dosing of MBS2320 over 12 weeks compared with placebo in participants with IPF on the following variables: Forced expiratory volume in 1 second (FEV1), FEV1/FVC ratio, Cough, Dyspnea, 36-Item Short Form Health Survey (SF-36), King’s Brief Interstitial Lung Disease (KBILD), Living with pulmonary fibrosis questionnaire (L-PF), Decline or increase in %FVC, Decline or increase in absolute FVC, 6-minute walking test (6MWT)
6. To evaluate the effect of daily oral dosing of MBS2320 over 12 weeks compared with placebo in participants with IPF on disease progression.

Conditions and MedDRA coding

Idiopathic Pulmonary Fibrosis

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. 1. Participant must be 40 years or older at the time of signing the informed consent.
2. 2. 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
3. 3. Has an FVC ≥45% of predicted.
4. 4. Has a DLCO corrected for hemoglobin ≥25% and ≤80% of predicted.
5. 5. Minimum distance on 6MWT of 150 meters.
6. 6. Has a FEV1/FVC ratio >0.70.
7. 7. 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.
8. 8. Male and female participants using contraception in line with local regulations regarding the methods of contraception for those participating in clinical studies (Appendix 4).
9. 9. 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.
10. 10. Has a life expectancy of at least 12 months (in the opinion of the investigator).
11. 11. According to the investigator’s best judgment, can comply with the requirements of the protocol

Exclusion criteria 35

1. 1. 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.
2. 10. 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.
3. 11. 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.
4. 12. 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).
5. 13. Have experienced clinically significant metabolic acidosis in the past.
6. 14. Is receiving systemic corticosteroids equivalent to prednisone >10 mg/day or equivalent within 2 weeks of baseline.
7. 15. Received azathioprine, cyclophosphamide, or cyclosporine A within 4 weeks of baseline.
8. 16. Baseline resting oxygen saturation is <89% on room air or supplemental oxygen up to a maximum of 4 L/min.
9. 17. 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.
10. 18. Has a known post bronchodilator (short acting beta agonist [SABA] – albuterol or salbutamol) increase in FEV1 of >10% and in FVC of >7.5%
11. 19. 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.
12. 2. 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.
13. 20. 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.
14. 21. 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.
15. 22. 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
16. 23. 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.
17. 24. Previously received MBS2320.
18. 25. Current use of tobacco products and/or vaping.
19. 26. Donated blood in the 90 days prior to screening.
20. 27. Prior GI surgeries or any GI procedures/conditions that may cause concerns with absorption of the study drug.
21. 28. History of major surgery (requiring regional block or general anesthesia) within 3 months prior to screening or planned major surgery during the study.
22. 29. 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.
23. 3. 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).
24. 30. 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.
25. 31. 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.
26. 32. Participants who are breastfeeding or lactating.
27. 33. Risk factors for severe COVID-19, which in the opinion of the Investigator would put the participant at risk by participating in the study
28. 4. Significant history of drug allergy, including to MBS2320 or excipients, as determined by the Investigator.
29. 5. Allergic reaction, anaphylaxis, or other reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis or leukopenia) to sulfonamide drugs.
30. 6. A significant history of alcoholism or drug/chemical abuse within 1 year prior to screening, as determined by the investigator.
31. 7. History of opportunistic, chronic, or recurrent infections including untreated latent tuberculosis.
32. 8. 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.
33. 9. 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.
34. 34. Participants who are committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.
35. 35. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in FVC versus placebo up to Week 12 or up to the point of discontinuation

Secondary endpoints 6

1. Change from baseline in %FVC up to Week 12
2. Change from baseline in %DLCO up to Week 12
3. Change from baseline up to Week 12 in primary and secondary endpoints
4. Time to first acute exacerbation up to week 12. Change from baseline in KCO and AV up to week 12
5. Change from baseline in FEV and FEV/FVC ration at week 4,8 and 12. Change from baseline in SF-36, KBKILD and L-PF at weeks 4,8 and 12
6. Proportion of participants with evidence of disease progression, defined as a decline in %FVC ≥10%, decline in %DLCO ≥15%, lung transplantation, or death.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Modern Biosciences Limited

Sponsor organisation

Modern Biosciences Limited

Address

2nd Floor, 3 Pancras Square 3 Pancras Square

City

London

Postcode

N1C 4AG

Country

United Kingdom

Scientific contact point

Organisation

Modern Biosciences Limited

Contact name

Lead Clinical Trial Manager

Public contact point

Organisation

Modern Biosciences Limited

Contact name

Lead Clinical Trial Manager

Third parties 8

Modern Biosciences Limited

Sponsor organisation

Modern Biosciences Limited

Address

2nd Floor, 3 Pancras Square 3 Pancras Square

City

London

Postcode

N1C 4AG

Country

United Kingdom

Scientific contact point

Organisation

Modern Biosciences Limited

Contact name

Lead Clinical Trial Manager

Public contact point

Organisation

Modern Biosciences Limited

Contact name

Lead Clinical Trial Manager

Third parties 8

Locations

6 EU/EEA countries · 31 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 5 · Art. 38 CTR

Application history

3 submissions — initial application plus substantial / non-substantial modifications