Efficacy and Safety Evaluation of Verekitug (UPB-101) in Chronic Rhinosinusitis with Nasal Polyps on Nasal Corticosteroids: A Randomized, Double-Blind, Placebo-Controlled Study
- Trial ID
- 2023-508231-31-00
- Protocol
- UPB-CP-03
- Sponsor
- Upstream Bio Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the effect of **verekitug (UPB-101)** on endoscopic Nasal Polyp Score (NPS) compared to placebo in participants with **Chronic Rhinosinusitis with Nasal Polyps**. This is clinically relevant as it aims to determine the efficacy of verekitug in reducing nasal polyp size, which is a significant concern in managing this condition.
Secondary objectives include:
- Assessing the effect of verekitug on Nasal Congestion Score (NCS) compared to placebo.
- Evaluating the impact on CT scan opacification of the sinuses compared to placebo.
- Determining the effect on loss of smell compared to placebo.
- Assessing the need for treatment with systemic corticosteroids or nasal polyp surgery compared to placebo.
- Evaluating the effect on total symptoms of Chronic Rhinosinusitis with Nasal Polyps compared to placebo.
- Assessing the safety and tolerability of verekitug compared to placebo.
Participants
The clinical trial involves a total of **64 participants** diagnosed with **Chronic Rhinosinusitis with Nasal Polyps** (CRSwNP). The study population includes both male and female subjects, aged between 18 to 75 years. Participants were selected based on specific criteria, including a physician diagnosis of CRSwNP for at least six months prior to the initial visit. The trial does not include a vulnerable population. Participants are required to have a stable standard of care treatment for CRSwNP for at least 30 days before the first visit and must demonstrate at least 70% compliance with mometasone furoate nasal spray or an equivalent therapy in the 14 days preceding the second visit. The trial population is not restricted by any specific lifestyle considerations such as diet or physical activity. Contraceptive use must align with local regulations for clinical study participants.
Plans and Procedures
The clinical trial is a **Phase 2**, randomized, double-blind, placebo-controlled, multi-center study designed to evaluate the efficacy and safety of **Verekitug (UPB-101)** in participants with **Chronic Rhinosinusitis with Nasal Polyps** (CRSwNP) who are on a background of nasal corticosteroids. The trial aims to assess the effect of Verekitug on endoscopic nasal polyp score (NPS) compared to placebo. The study is expected to commence recruitment on July 15, 2024, and conclude by May 21, 2025, with a total duration of approximately 24 weeks for each participant.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (18 to 75 years), a physician diagnosis of CRSwNP for at least six months, and stable standard of care treatment for at least 30 days prior to the first visit. Following the screening, participants will be randomized to receive either the investigational product or placebo, administered as a subcutaneous injection. The primary endpoint is the change from baseline in NPS at Week 24, with secondary endpoints including changes in nasal congestion score (NCS), sinus opacification, and the proportion of participants requiring systemic corticosteroids or nasal polyp surgery.
Study visits will include baseline assessments, regular follow-up visits to monitor safety and efficacy, and an end-of-study visit. Participants will be required to maintain at least 70% compliance with background mometasone furoate nasal spray therapy. The expected length of participant involvement is 24 weeks, with conditions for early termination including non-compliance with study procedures, withdrawal of consent, or adverse events that necessitate discontinuation. Safety assessments will include adverse events (AEs), serious adverse events (SAEs), physical examinations, clinical laboratory assessments, vital signs, and electrocardiograms (ECGs) conducted throughout the study duration, including the follow-up period.
Treatment
The clinical trial involves the administration of **Verekitug (UPB-101)**, a **solution for injection** containing a **human IgG1 kappa monoclonal antibody against CRLF2**. This experimental medication is provided in a pharmaceutical form suitable for **subcutaneous use**. The dosing regimen specifies a maximum daily dose of 100 mg, with a total maximum dose of 100 mg over a treatment period of up to 24 weeks. The administration of the drug is conducted under controlled conditions to ensure participant compliance and accurate monitoring of therapeutic outcomes. The investigational product is developed by UPSTREAM BIO, INC., and is not formulated for pediatric use.
In addition to the experimental treatment, the study employs a **placebo** control, referred to as **Veritikug (upb-101) matching solution for subcutaneous injection with no active treatment**. This placebo is designed to match the experimental medication in appearance and administration route, ensuring the integrity of the double-blind study design. The placebo is administered with the same frequency and under similar conditions as the active treatment to maintain consistency across the study arms. Compliance with the placebo regimen is monitored in parallel with the active treatment to ensure the reliability of the trial results.
Efficacy
Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint is the change from baseline at Week 24 in the **Nasal Polyp Score (NPS)**. Secondary endpoints include changes from baseline at Week 24 in the Nasal Congestion Score (NCS) evaluated by the Nasal Polyp Symptom Diary (NPSD), opacification of sinuses measured by the Lund-Mackay (LMK) score, and the Daily Symptom Score (DSS) evaluated by the NPSD. Additionally, the proportion of participants requiring systemic corticosteroids or nasal polyposis surgery, time to nasal polyposis surgery and/or time to systemic corticosteroids for nasal polyposis up to Week 24, and changes from baseline at Week 24 in the NPSD Total Symptom Score (TSS) will be evaluated. Safety assessments will include adverse events (AEs), serious adverse events (SAEs), physical examinations, clinical laboratory assessments, vital signs, and electrocardiograms (ECGs) from baseline over the study duration, including the follow-up period.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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.
- Participant is aged 18 to 75 years of age (inclusive) at the time of signing the ICF.
- Participant has physician diagnosed CRSwNP for at least 6 months prior to Visit 1 that fulfils all mentioned in the Protocol, Section 5.1.
- 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).
- Stable standard of care treatment for CRSwNP for at least 30 days prior to Visit 1.
- At Visit 2, at least 21 days of background mometasone furoate nasal spray (MFNS) (or equivalent) background therapy.
- ≥70% diary compliance for MFNS (or equivalent) in the 14 days prior to Visit 2.
- Contraceptive use by the participant must be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
Exclusion Criteria
- 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.
- Expected need, in the opinion of the investigator, for NP surgery within 12 weeks of Visit 2.
- Comorbid asthma having forced expiratory volume in 1 second (FEV1) 50% or less of predicted normal at Visit 1.
- 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.
- 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.
- Previous exposure to verekitug (UPB-101) or known allergy/sensitivity to any of its excipients.
- 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.
- Any experimental mAb within 5 half-lives or within 6 months before Visit 1 if the half-life- was unknown.
- Leukotriene antagonists/modifiers at Visit 1 unless used as a continuous treatment at same dose for at least 30 days prior to Visit 1.
- Allergen immunotherapy within 12 weeks (unless maintenance dose) prior to Visit 1 or plans to begin therapy or change dosing during the study.
- Administration of the T2 cytokine inhibitor suplatast tosilate within 15 days prior to Visit 1.
- Oral, IV, or intramuscular steroid within 8 weeks prior to Visit 1. Intrathecal or intra-articular steroids are permitted.
- Treatment with a live (attenuated) vaccine within 12 weeks before Visit 2.
- Any vaccination within the Screening Period.
- 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.
- 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.
- 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.
- 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.
- 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).
- 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).
- History compatible with, or diagnosis of, a parasitic infection and has not been treated or has not responded to the standard of care therapy.
- Type I or II diabetes under poor glucose control, as assessed by the Investigator.
- 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.
- History of malignancy of any type, other than in situ cervical cancer or surgically excised non-melanomatous skin cancers, within 5 years before Visit
- 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.
- Immunodeficiency disorder or positive for human immunodeficiency virus (HIV) antibodies.
- Positive hepatitis B surface antigen (HBsAg), or hepatitis C antibodies.
- Known active tuberculosis at Visit 1. A tuberculosis test may be performed if required based on local guidelines.
- History of chronic alcohol or substance use disorder within 12 months prior to Visit 1.
- 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.
- Positive coronavirus disease 2019 (COVID-19) test within 28 days before Visit 1.
- 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.
- 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.
- 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.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Czechia | Not Recruiting | 15 Jul 2024 | 4 |
 Germany | Not Recruiting | 15 Jul 2024 | 6 |
 Poland | Not Recruiting | 15 Jul 2024 | 20 |
 Spain | Not Recruiting | 15 Jul 2024 | 15 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Veritikug (upb-101) matching solution for subcutaneous injection with no active treatment | Placebo | N/A | — | — | — | N/A |
VerekitugUPB-101 | Test | SOLUTION FOR INJECTION | SUBCUTANEOUS USE | 100 | 24 | PRD10995765 |