## Protocol Section
### Identification Module
**NCT ID:** NCT06196879

**Brief Title:** A Study to Investigate the Efficacy and Safety of Verekitug (UPB-101) in Adult Participants With Severe Asthma (VALIANT)

**Official Title:** A Phase 2, Randomized, Double-blind, Placebo-controlled, Multi-center, Dose-ranging Study to Evaluate the Efficacy and Safety of Verekitug (UPB-101) in Adult Participants With Severe Asthma (VALIANT)

#### Organization Study ID Info
**ID:** UPB-CP-04
#### Organization
**Class:** INDUSTRY
**Full Name:** Upstream Bio Inc.
#### Secondary ID Infos
**Domain:** EUCT
**ID:** 2023-507410-27-00
**Type:** OTHER
### Status Module
#### Completion Date
**Date:** 2026-06-11

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-04-23

**Type:** ACTUAL

**Last Update Submit Date:** 2024-04-22

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2026-02-19

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-02-27

**Type:** ACTUAL

**Status Verified Date:** 2024-04

#### Study First Post Date
**Date:** 2024-01-09
**Type:** ACTUAL
**Study First Submit Date:** 2023-12-24
**Study First Submit QC Date:** 2023-12-24
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Upstream Bio Inc.

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** The purpose of this study is to evaluate the efficacy and safety of verekitug (UPB-101) in participants with severe asthma. The study will evaluate the incidence of asthma exacerbations, other pharmacodynamic (PD) parameters such as lung function and asthma control, and the safety and tolerability of verekitug (UPB-101) compared to placebo.

**Detailed Description:** This is a multicenter, randomized, placebo-controlled, parallel group study to assess the efficacy and safety of verekitug (UPB-101) administered subcutaneously (SC). A total of approximately 436 adult participants with severe asthma are planned for enrolment and will be randomized in a 1:1:1:1 ratio to receive verekitug (UPB-101) at doses of 100 mg every 12 weeks (Q12W), 400 mg every 24 weeks (Q24W), and 100 mg every 24 weeks (Q24W), or placebo administered SC. In order to maintain the blinding of different doses, all participants will receive 2 SC injections at each dosing visit. This study consists of a Screening/Run-In Period (approximately 4 weeks), Treatment Period (up to 60 weeks with a minimum of 24 weeks) and Follow-up Period (ending approximately 16 weeks after the last administration of study intervention).

### Conditions Module

**Conditions:**

- Severe Asthma

**Keywords:**

- VALIANT

- Respiratory Tract Diseases

- Bronchial Diseases

- Asthma

- Lung Diseases

- Uncontrolled Asthma

- Severe Asthma

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** QUADRUPLE

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 436

**Type:** ESTIMATED

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Participants will receive 0.5 milliliter (mL) of verekitug (UPB-101) formulated solution (containing 100 milligrams \[mg\] of verekitug \[UPB-101\]) and 2.0 mL of placebo subcutaneously in two separate injections every 12 weeks up to Week 48.

**Intervention Names:**

- Drug: Verekitug (UPB-101)

- Drug: Placebo

**Label:** Verekitug (UPB-101): 100 mg Q12W / Placebo

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Participants will receive 2.0 mL of verekitug (UPB-101) formulated solution (containing 400 mg of verekitug \[UPB-101\]) and 0.5 mL of placebo subcutaneously in two separate injections every 24 weeks up to Week 48. Participants will also receive 2 mL and 0.5 mL of placebo subcutaneously in two separate injections at Weeks 12 and 36 visits.

**Intervention Names:**

- Drug: Verekitug (UPB-101)

- Drug: Placebo

**Label:** Verekitug (UPB-101): 400 mg Q24W / Placebo

**Type:** EXPERIMENTAL

#### Arm Group 3

**Description:** Participants will receive 0.5 mL of verekitug (UPB-101) formulated solution (containing 100 mg of verekitug \[UPB-101\]) and 2.0 mL of placebo subcutaneously in two separate injections every 24 weeks up to Week 48. Participants will also receive 2 mL and 0.5 mL of placebo subcutaneously in two separate injections at Weeks 12 and 36 visits.

**Intervention Names:**

- Drug: Verekitug (UPB-101)

- Drug: Placebo

**Label:** Verekitug (UPB-101): 100 mg Q24W / Placebo

**Type:** EXPERIMENTAL

#### Arm Group 4

**Description:** Participants will receive 0.5 mL of matching placebo and 2.0 mL of matching placebo subcutaneously in two separate injections every 12 weeks up to Week 48.

**Intervention Names:**

- Drug: Placebo

**Label:** Placebo

**Type:** PLACEBO_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Verekitug (UPB-101): 100 mg Q12W / Placebo

- Verekitug (UPB-101): 100 mg Q24W / Placebo

- Verekitug (UPB-101): 400 mg Q24W / Placebo

**Description:** Verekitug (UPB-101) formulated solution

**Name:** Verekitug (UPB-101)

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Placebo

- Verekitug (UPB-101): 100 mg Q12W / Placebo

- Verekitug (UPB-101): 100 mg Q24W / Placebo

- Verekitug (UPB-101): 400 mg Q24W / Placebo

**Description:** Verekitug (UPB-101) matching placebo

**Name:** Placebo

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** An asthma exacerbation is defined as a worsening of asthma that required treatment with systemic (oral or intravenous) corticosteroids for at least three consecutive days or a single depo-injectable dose of corticosteroids or an emergency room (ER) or urgent care visit that required systemic corticosteroids or an admission to an inpatient facility and/or evaluation and treatment in a healthcare facility for greater than or equal to 24 hours.

**Measure:** Annual Asthma Exacerbation Rate (AAER)

**Time Frame:** Baseline up to Week 60

#### Secondary Outcomes

**Description:** Spirometry will be performed pre-bronchodilator (BD) to measure lung function. FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration.

**Measure:** Change from Baseline in Forced Expiratory Volume in 1 Second (FEV1) of Pre-bronchodilator (Pre-BD) to Week 60

**Time Frame:** Baseline to Week 60

**Description:** Standardized single breath FeNO test is performed to evaluate airway inflammation.

**Measure:** Change from Baseline in Fractional exhaled nitric oxide (FeNO) to Week 60

**Time Frame:** Baseline to Week 60

**Description:** ACQ-6 is a participant-reported questionnaire to assess asthma control with 6 items assessing night-time waking, symptoms on waking, activity limitation, shortness of breath, wheeze, and rescue short-acting beta agonist use. Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The ACQ-6 score is the mean of the responses.

**Measure:** Change from Baseline in Asthma Control Questionnaire-6 (ACQ-6) to Week 60

**Time Frame:** Baseline to Week 60

**Description:** An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

**Measure:** Number of Participants with Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs

**Time Frame:** Up to Week 64

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Signed, dated, and received a copy of the Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved written informed consent form (ICF).
* Age 18 to 75 years of age (inclusive) at the time of consent.
* Physician-diagnosed asthma for at least 12 months prior to Visit 1.
* Participant has evidence of bronchodilator (BD) reversibility as documented by either historical reversibility (within 12 months prior to study entry) or reversibility during screening.
* Documented treatment with a total daily dose of either medium or high dose inhaled corticosteroids (ICS) for at least 3 months. Participants on medium dose ICS must also have been taking at least one additional maintenance asthma controller medication for at least 3 months.
* Documented history of asthma exacerbation(s) within 12 months of Visit 1.
* Asthma Control Questionnaire-6 (ACQ-6) score greater than or equal to (\>=) 1.5 at screening and randomization.
* Participant must have a pre-BD FEV1 value of \>=30 percent (%) and \<=80% predicted at Screening.
* Minimum compliance with daily diary and background asthma medication(s) as captured in the daily diary during the Run-in Period.
* Agrees to follow the required contraceptive techniques/methods.
* Female or male participant agrees not to donate eggs or sperm, respectively, for a period of 120 days after the last dose of the study drug intervention or at the Final Visit, whichever occurs last.

Exclusion Criteria:

* Inpatient hospitalization due to asthma at any time within 4 weeks prior to Visit 1 or during the Screening/Run-in Period.
* Previous exposure to verekitug (UPB-101) or known allergy/sensitivity to any of its excipients.
* Previous biologics for asthma treatment for which the appropriate washout period is not fulfilled prior to Visit 1. If the half-life is not known, a 24-week washout period prior to Visit 1 should be applied.
* Allergen immunotherapy (unless maintenance dose) within 12 weeks prior to Visit 1 or plans to begin therapy or change dosing during the study.
* For participants taking oral corticosteroids (OCS), the dose has not been stable for at least 2 weeks prior to Visit 1 and/or is \>10 milligram (mg) daily, or \>20 mg every other day.
* Evidence of active or suspected bacterial, viral, fungal, or parasitic infections within 2 weeks prior to Visit 1.
* History compatible with or diagnosis of a parasitic infection and has not been treated or has not responded to standard of care therapy.
* Current tobacco smokers, nicotine vapers (including electronic cigarettes), snuff users or participants with a smoking history \>=10 pack years. (Former nicotine smokers with a smoking history of \<10 pack years, former nicotine vapers and former snuff users must have stopped for at least 6 months prior to Visit 1 to be eligible).
* Positive coronavirus disease 2019 (COVID-19) test with lower respiratory tract symptoms 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.

**Maximum Age:** 75 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** clinicaltrials@upstreambio.com

**Name:** Upstream Bio Clinical Trials Information (Privacy Notice: https://www.upstreambio.com/privacy)

**Phone:** 888-446-3130

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Birmingham

**Country:** United States

**Facility:** AllerVie Clinical Research

**State:** Alabama

**Status:** RECRUITING

**Zip:** 35209

**Location 2:**

**City:** Bakersfield

**Country:** United States

**Facility:** Kern Research, Inc.

**State:** California

**Status:** RECRUITING

**Zip:** 93301

**Location 3:**

**City:** Los Angeles

**Country:** United States

**Facility:** Velocity Clinical Research - Lafayette LA

**State:** California

**Status:** RECRUITING

**Zip:** 70508

**Location 4:**

**City:** Newport Beach

**Country:** United States

**Facility:** Newport Native MD Inc

**State:** California

**Status:** RECRUITING

**Zip:** 92663

**Location 5:**

**City:** Northridge

**Country:** United States

**Facility:** California Medical Research Associates Inc.

**State:** California

**Status:** RECRUITING

**Zip:** 91324

**Location 6:**

**City:** Upland

**Country:** United States

**Facility:** Integrated Research of Inland Inc

**State:** California

**Status:** RECRUITING

**Zip:** 91786

**Location 7:**

**City:** Walnut Creek

**Country:** United States

**Facility:** Allergy & Asthma Clinical Research

**State:** California

**Status:** RECRUITING

**Zip:** 94598

**Location 8:**

**City:** Westminster

**Country:** United States

**Facility:** Allianz Research Institute

**State:** California

**Status:** RECRUITING

**Zip:** 92683

**Location 9:**

**City:** Miami

**Country:** United States

**Facility:** Health and Life Research Institute, LLC

**State:** Florida

**Status:** RECRUITING

**Zip:** 33155

**Location 10:**

**City:** Miami

**Country:** United States

**Facility:** Phoenix Medical Research

**State:** Florida

**Status:** RECRUITING

**Zip:** 33165

**Location 11:**

**City:** Miami

**Country:** United States

**Facility:** Research Institute of South Florida

**State:** Florida

**Status:** RECRUITING

**Zip:** 33173

**Location 12:**

**City:** Miami

**Country:** United States

**Facility:** Clinical Site Partners, LLC dba Flourish Research

**State:** Florida

**Status:** RECRUITING

**Zip:** 33176

**Location 13:**

**City:** Miami

**Country:** United States

**Facility:** Clinical Site Partners

**State:** Florida

**Status:** RECRUITING

**Zip:** 33176

**Location 14:**

**City:** Miami

**Country:** United States

**Facility:** Nouvelle Clinical Research

**State:** Florida

**Status:** RECRUITING

**Zip:** 33189

**Location 15:**

**City:** Orlando

**Country:** United States

**Facility:** Anderson Allergy And Asthma, PA

**State:** Florida

**Status:** RECRUITING

**Zip:** 32806

**Location 16:**

**City:** Plantation

**Country:** United States

**Facility:** Edward Jenner Research Group, LLC

**State:** Florida

**Status:** RECRUITING

**Zip:** 33317

**Location 17:**

**City:** Winter Park

**Country:** United States

**Facility:** Clinical Site Partners dba Flourish research

**State:** Florida

**Status:** RECRUITING

**Zip:** 32789

**Location 18:**

**City:** Boise

**Country:** United States

**Facility:** Treasure Valley Medical Research

**State:** Idaho

**Status:** RECRUITING

**Zip:** 83706

**Location 19:**

**City:** Meridian

**Country:** United States

**Facility:** Velocity Clinical Research - Meridian

**State:** Idaho

**Status:** RECRUITING

**Zip:** 83642

**Location 20:**

**City:** White Marsh

**Country:** United States

**Facility:** Chesapeake Clinical Research Inc

**State:** Maryland

**Status:** RECRUITING

**Zip:** 21162

**Location 21:**

**City:** Farmington Hills

**Country:** United States

**Facility:** Pulmonary Research Institute of Southeast Michigan

**State:** Michigan

**Status:** RECRUITING

**Zip:** 48336

**Location 22:**

**City:** Flint

**Country:** United States

**Facility:** AA Medical Research Center

**State:** Michigan

**Status:** NOT_YET_RECRUITING

**Zip:** 48504

**Location 23:**

**City:** Flint

**Country:** United States

**Facility:** AA MRC

**State:** Michigan

**Status:** RECRUITING

**Zip:** 48504

**Location 24:**

**City:** Las Vegas

**Country:** United States

**Facility:** M3 Wake Research

**State:** Nevada

**Status:** RECRUITING

**Zip:** 89106

**Location 25:**

**City:** Bronx

**Country:** United States

**Facility:** Urban Health Plan INC

**State:** New York

**Status:** RECRUITING

**Zip:** 10459

**Location 26:**

**City:** Huntersville

**Country:** United States

**Facility:** Advanced Respiratory and Sleep Medicine LLC

**State:** North Carolina

**Status:** RECRUITING

**Zip:** 28078

**Location 27:**

**City:** Toledo

**Country:** United States

**Facility:** Toledo Institute of Clinical Research Inc

**State:** Ohio

**Status:** RECRUITING

**Zip:** 43617

**Location 28:**

**City:** Edmond

**Country:** United States

**Facility:** OK Clinical Research, LLC

**State:** Oklahoma

**Status:** RECRUITING

**Zip:** 73034

**Location 29:**

**City:** Medford

**Country:** United States

**Facility:** Velocity Clinical Research - Medford

**State:** Oregon

**Status:** RECRUITING

**Zip:** 97504

**Location 30:**

**City:** Anderson

**Country:** United States

**Facility:** Velocity Clinical Research - Anderson

**State:** South Carolina

**Status:** RECRUITING

**Zip:** 29621

**Location 31:**

**City:** Charleston

**Country:** United States

**Facility:** WR-Notus Clinical Research, LLC

**State:** South Carolina

**Status:** RECRUITING

**Zip:** 29414

**Location 32:**

**City:** Spartanburg

**Country:** United States

**Facility:** Velocity Clinical Research - Spartanburg

**State:** South Carolina

**Status:** RECRUITING

**Zip:** 29303

**Location 33:**

**City:** Chattanooga

**Country:** United States

**Facility:** WR-ClinSearch, LLC

**State:** Tennessee

**Status:** RECRUITING

**Zip:** 37421

**Location 34:**

**City:** Dallas

**Country:** United States

**Facility:** Alina Clinical Trials, LLC

**State:** Texas

**Status:** RECRUITING

**Zip:** 75225

**Location 35:**

**City:** Dallas

**Country:** United States

**Facility:** AARA Research Center

**State:** Texas

**Status:** RECRUITING

**Zip:** 75231

**Location 36:**

**City:** El Paso

**Country:** United States

**Facility:** El Paso Pulmonary Association

**State:** Texas

**Status:** RECRUITING

**Zip:** 79902

**Location 37:**

**City:** Houston

**Country:** United States

**Facility:** Greater Houston Memorial Pulmonary and Sleep

**State:** Texas

**Status:** RECRUITING

**Zip:** 77008

**Location 38:**

**City:** McKinney

**Country:** United States

**Facility:** Metroplex Pulmonary and Sleep Center Drive

**State:** Texas

**Status:** RECRUITING

**Zip:** 75069

**Location 39:**

**City:** Tomball

**Country:** United States

**Facility:** DM Clinical Tomball

**State:** Texas

**Status:** RECRUITING

**Zip:** 77375

**Location 40:**

**City:** West Jordan

**Country:** United States

**Facility:** Velocity Clinical Research

**State:** Utah

**Status:** RECRUITING

**Zip:** 84088

**Location 41:**

**City:** Ajax

**Country:** Canada

**Facility:** Dynamic Drug Advancement

**State:** Ontario

**Status:** RECRUITING

**Zip:** L1S 2J5

**Location 42:**

**City:** Ottawa

**Country:** Canada

**Facility:** Ottawa Allergy Research Corp

**State:** Ontario

**Status:** RECRUITING

**Zip:** K1H 1E4

**Location 43:**

**City:** Toronto

**Country:** Canada

**Facility:** Toronto Allergists

**State:** Ontario

**Status:** RECRUITING

**Zip:** M5G1E2

**Location 44:**

**City:** Winchester

**Country:** Canada

**Facility:** Winchester Hospital

**State:** Ontario

**Status:** RECRUITING

**Zip:** K0C 2K0

#### Overall Officials

**Official 1:**

**Affiliation:** Upstream Bio

**Name:** James C Lee, MD

**Role:** STUDY_DIRECTOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000001982

- Term: Bronchial Diseases

- ID: D000012140

- Term: Respiratory Tract Diseases

- ID: D000008173

- Term: Lung Diseases, Obstructive

- ID: D000008171

- Term: Lung Diseases

- ID: D000012130

- Term: Respiratory Hypersensitivity

- ID: D000006969

- Term: Hypersensitivity, Immediate

- ID: D000006967

- Term: Hypersensitivity

- ID: D000007154

- Term: Immune System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC08

- Name: Respiratory Tract (Lung and Bronchial) Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC20

- Name: Immune System Diseases

### Condition Browse Module - Browse Leaves

- ID: M11168

- Name: Lung Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M4556

- Name: Asthma

- Relevance: HIGH

- As Found: Asthma

- ID: M14977

- Name: Respiratory Tract Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5258

- Name: Bronchial Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M11170

- Name: Lung Diseases, Obstructive

- Relevance: LOW

- As Found: Unknown

- ID: M10018

- Name: Hypersensitivity

- Relevance: LOW

- As Found: Unknown

- ID: M14967

- Name: Respiratory Hypersensitivity

- Relevance: LOW

- As Found: Unknown

- ID: M10020

- Name: Hypersensitivity, Immediate

- Relevance: LOW

- As Found: Unknown

- ID: M10200

- Name: Immune System Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000001249

- Term: Asthma

### Intervention Browse Module - Browse Branches

- Abbrev: PhSol

- Name: Pharmaceutical Solutions

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M21860

- Name: Pharmaceutical Solutions

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-24
