A Study to Investigate the Efficacy and Safety of Verekitug (UPB-101) in Participants with Chronic Rhinosinusitis with Nasal Polyps on a Background of Nasal Corticosteroids (VIBRANT)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Upstream Bio Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

24 Jul 2024 → 23 Jul 2025

Decision date (initial)

2024-09-19

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-508231-31-00

ClinicalTrials.gov

NCT06164704

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To assess the effect of verekitug (UPB-101) on endoscopic NPS compared to placebo

Secondary objectives 6

1. To assess the effect of verekitug (UPB-101) on NCS compared to placebo
2. To assess the effect of verekitug (UPB-101) on CT scan opacification of the sinuses compared to placebo
3. To assess the effect of verekitug (UPB-101) on loss of smell compared to placebo
4. To assess the effect of verekitug (UPB-101) on the need for treatment with systemic corticosteroids or NP surgery compared to placebo
5. To assess the effect of verekitug (UPB-101) on total symptoms of CRSwNP compared to placebo
6. To assess safety and tolerability of verekitug (UPB-101) compared to placebo

Conditions and MedDRA coding

Chronic Rhinosinusitis with Nasal Polyps

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Participant has signed, dated and received a copy of the Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved written informed consent form (ICF) as described in Appendix 1 (Section 10.1.3), which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
2. Participant is aged 18 to 75 years of age (inclusive) at the time of signing the ICF.
3. Participant has physician diagnosed CRSwNP for at least 6 months prior to Visit 1 that fulfils all mentioned in the Protocol, Section 5.1.
4. Participant has at least one of the following: o In the 24 months prior to Visit 1, had a documented exacerbation of nasal polyposis requiring treatment with systemic corticosteroid, and/or; o A medical contraindication/intolerance to systemic corticosteroid, and/or; o Had prior surgery for NP (cannot be within 6 months prior to Visit 1 – see Section 5.2).
5. Stable standard of care treatment for CRSwNP for at least 30 days prior to Visit 1.
6. At Visit 2, at least 21 days of background mometasone furoate nasal spray (MFNS) (or equivalent) background therapy.
7. ≥70% diary compliance for MFNS (or equivalent) in the 14 days prior to Visit 2.
8. Contraceptive use by the participant must be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Exclusion criteria 34

1. Participants are excluded from the study if any of the following criteria apply: Has undergone any intranasal and/or sinus surgery (including polypectomy) within 6 months prior to Visit 1.
2. Expected need, in the opinion of the investigator, for NP surgery within 12 weeks of Visit 2.
3. Comorbid asthma having forced expiratory volume in 1 second (FEV1) 50% or less of predicted normal at Visit 1.
4. Conditions making participants non-evaluable at Visit 1 for the primary endpoint such as sino-nasal or sinus surgery changing the lateral wall structure of the nose, antrochoanal polyps, nasal septal deviation occluding at least one nostril, acute sinusitis, upper respiratory infection, ongoing rhinitis medicamentosa, fungal rhinosinusitis, nasal cavity benign or malignant tumors.
5. Concurrent participation in a clinical study or has been treated with an investigational drug within 28 days or 5 half-lives, whichever is longer, prior to Visit 1.
6. Previous exposure to verekitug (UPB-101) or known allergy/sensitivity to any of its excipients.
7. Biologic therapy or systemic immunosuppressant to treat inflammatory disease or autoimmune disease within 6 months or 5 half-lives before Visit 1, whichever is longer, with the exception of oral corticosteroids. Treatment with cyclophosphamide and rituximab within 12 months of Visit 1.
8. Any experimental mAb within 5 half-lives or within 6 months before Visit 1 if the half-life- was unknown.
9. Leukotriene antagonists/modifiers at Visit 1 unless used as a continuous treatment at same dose for at least 30 days prior to Visit 1.
10. Allergen immunotherapy within 12 weeks (unless maintenance dose) prior to Visit 1 or plans to begin therapy or change dosing during the study.
11. Administration of the T2 cytokine inhibitor suplatast tosilate within 15 days prior to Visit 1.
12. Oral, IV, or intramuscular steroid within 8 weeks prior to Visit 1. Intrathecal or intra-articular steroids are permitted.
13. Treatment with a live (attenuated) vaccine within 12 weeks before Visit 2.
14. Any vaccination within the Screening Period.
15. For participants with comorbid asthma, inhaled corticosteroid (ICS) total daily dose > 1000 μg fluticasone propionate (or equivalent dose of another ICS [Section 10.5]) or participants not on a stable dose of ICSs for ≥ 30 days prior to Visit 1.
16. Abnormal medical history, physical finding or safety finding that in the opinion of the Investigator may obscure the study data or interfere with the participant’s safety.
17. Any clinical laboratory test result outside of the reference ranges considered by the Investigator as clinically significant and that may obscure the study data or interfere with the participant’s safety.
18. Allergic granulomatous angiitis (Churg-Strauss syndrome), granulomatosis with polyangiitis (Wegener's granulomatosis), Young's syndrome, Kartagener's syndrome or other dyskinetic ciliary syndromes, concomitant cystic fibrosis.
19. Participant with comorbid asthma that also has a history or evidence of a clinically significant pulmonary condition (other than asthma), including significant restrictive findings on pulmonary function testing, chronic bronchitis, emphysema, bronchiectasis, pulmonary fibrosis, or any other related condition that may obscure the study data (e.g., gastro-esophageal reflux and vocal cord paralysis/dysfunction).
20. Evidence of active or suspected bacterial, viral, fungal, or parasitic infections within 2 weeks prior to Visit 2 (e.g., sinusitis, common cold, viral syndrome, flu-like symptoms).
21. History compatible with, or diagnosis of, a parasitic infection and has not been treated or has not responded to the standard of care therapy.
22. Type I or II diabetes under poor glucose control, as assessed by the Investigator.
23. Estimated glomerular filtration rate of < 60 mL/min/1.73 m2 using the Chronic Kidney Disease Epidemiology Collaboration equation with correction factor for Black/African American participants.
24. History of malignancy of any type, other than in situ cervical cancer or surgically excised non-melanomatous skin cancers, within 5 years before Visit
25. Participant underwent surgery requiring general anesthesia within 8 weeks of Visit 1, or surgery without full recovery within 4 weeks of Visit 1, or donated blood or blood products, experienced loss of blood ≥500 mL or received blood products within 8 weeks of Visit 1.
26. Immunodeficiency disorder or positive for human immunodeficiency virus (HIV) antibodies.
27. Positive hepatitis B surface antigen (HBsAg), or hepatitis C antibodies.
28. Known active tuberculosis at Visit 1. A tuberculosis test may be performed if required based on local guidelines.
29. History of chronic alcohol or substance use disorder within 12 months prior to Visit 1.
30. Current tobacco smokers, nicotine vapers (including electronic cigarettes), snuff users or participants who have smoked and/or vaped and/or used snuff within the last 6 months prior to Visit 1.
31. Positive coronavirus disease 2019 (COVID-19) test within 28 days before Visit 1.
32. Pregnant or breastfeeding or planning to become pregnant or breastfeed during the study or unwilling to use adequate birth control, if of reproductive potential and sexually active.
33. Participant is an employee, consultant, and/or immediate family member (i.e., first degree relative, spouse, adoptee, or legal dependent) of the site or the Sponsor.
34. Participant is unreliable; incapable of adhering to the protocol and visit schedule according to the judgement of the Investigator; or has any disorder that may compromise their ability to give informed consent.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from Baseline at Week 24 in NPS

Secondary endpoints 7

1. Change from Baseline at Week 24 in the NCS evaluated by the NPSD
2. Change from Baseline at Week 24 in opacification of sinuses measured by LMK
3. Change from Baseline at Week 24 in DSS evaluated by the NPSD
4. Proportion of participants requiring systemic corticosteroids or NP surgery
5. Time to nasal polyposis surgery and/or time to systemic corticosteroids for nasal polyposis up to Week 24
6. Change from Baseline at Week 24 in NPSD TSS
7. AEs, SAEs, physical examinations, clinical laboratory assessments, vital signs, and ECGs from Baseline over study duration, including the Follow-Up Period

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Upstream Bio Inc.

Sponsor organisation

Upstream Bio Inc.

Address

890 Winter Street Suite 200

City

Waltham

Postcode

02451-1490

Country

United States

Scientific contact point

Organisation

Upstream Bio Inc.

Contact name

Kiran Patel

Public contact point

Organisation

Upstream Bio Inc.

Contact name

Kiran Patel

Third parties 4

Locations

4 EU/EEA countries · 15 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 56 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

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