HUMAN IGG1 LAMBDA FAB FRAGMENT AGAINST THYMIC STROMAL LYMPHOPOIETIN for Asthma

Inclusion criteria

• {"criterion_text":"- Patient must be 18 to 80 years of age inclusive, at the time of signing the ICF"}
• {"criterion_text":"- Pre-BD FEV1 ≥ 40% at both Visit 1 and Visit 2."}
• {"criterion_text":"- A pre-BD/pre-study intervention dose FEV1 at Visit 2 that has not increased by ≥ 400 ml from the pre-BD FEV1 recorded at Visit 1."}
• {"criterion_text":"- Patient has documented evidence of any of the following: (a) A history of 1 severe exacerbation within the last 12 months and either: (i) FeNO ≥ 25 ppb at the screening and randomisation visits (Visits 1 and 2) (ii) Eosinophil count ≥ 150 cells/µL, recorded at any point in the 12 months up to and including the Screening Visit (local testing can be carried out to confirm eligibility if eosinophil count not available in medical records within the last 12 months). (b) A history of ≥ 2 severe exacerbations within 12 months of Visit 1. A severe exacerbation is defined as an episode of symptoms of asthma worsening that results in at least one of the following: OCS use for 3 consecutive days, inpatient (≥ 24 hours) hospitalisation for asthma or emergency room or equivalent visit for asthma that results in systemic CS use."}
• {"criterion_text":"- At least 80% compliance with usual asthma background medication during the run-in period based on the daily asthma ePROs."}
• {"criterion_text":"- Minimum 80% compliance with daily assessments. Compliance is defined as completing the daily ePROs and PEF measurements (morning and evening) at least 80% of the time during the 14-day period prior to the randomisation visit (minimum of 11 days) preceding Vi"}
• {"criterion_text":"- Any patient at GINA step 5 (i.e. on high dose ICS plus LABA) for which an injectable biologic therapy for asthma is indicated (according to local prescribing guidance) must meet the following to be included Be unable or unwilling to receive an injectable biologic, or for whom such treatment is considered contraindicated or inappropriate in the opinion of the investigator. Documentation must be provided in the source records"}
• {"criterion_text":"- BMI within the range 18-37 kg/m2 (inclusive) at the time of signing the informed consent at Visit 1 and at Visit 2."}
• {"criterion_text":"- Female patients: (a) All FOCBP must have a negative serum pregnancy test result at the Screening Visit (Visit 1) and a negative urine pregnancy test on the day of randomisation (prior to randomisation; Visit 2) and must not be lactating. (b) Females of non-childbearing potential who are < 55 years old must fulfil one of the following criteria at the Screening Visit: (i) Post-menopausal, defined as amenorrhoea for ≥ 12 months following cessation of all exogenous hormonal treatments and FSH levels in the post-menopausal range (historical data for FSH will be accepted). (ii) Permanent sterilisation includes hysterectomy, bilateral oophorectomy, and bilateral salpingectomy at least 6 weeks before screening and is confirmed by the medical records or follow-up hormone level assessment. Bilateral tubal ligation is not acceptable. (c) For females aged ≥ 55 years, post-menopausal is defined as having a history of ≥ 12 months amenorrhea, without an alternative cause, following cessation of all exogenous hormonal treatments. (d) FOCBP must be willing to use highly effective contraception measures with low user dependency from signing the ICF until 20 days after last dose of study intervention. FOCBP should be stable on their chosen method of birth control for at least 3 months before first dosing."}
• {"criterion_text":"- Male patients: (a) Male patients and their FOCBP partner must be willing to use a highly effective contraception measure and should refrain from donating sperm or fathering a child from the first day of dosing until at least 20 days after last dose of study intervention."}
• {"criterion_text":"- Capable of giving signed informed consent."}
• {"criterion_text":"- Provision of signed and dated written Optional Genomics Initiative Research Information and Consent Form prior to collection of samples for optional genomics initiative research that supports the Genomic Initiative."}
• {"criterion_text":"- Documented physician diagnosis of asthma for at least 12 months, as evidenced by any of the following: (a) Post-BD reversibility of FEV1 ≥ 12% and ≥ 200 mL within 5 years prior to Visit 1, or (b) PEF average daily variability > 10% over a 2-week period within 5 years prior to Visit 1, or (c) Variability of FEV1 > 12% and 200 mL between any 2 clinical visits within 5 years prior to Visit 1, or (d) Positive bronchial challenge test within 5 years prior to Visit 1. A positive test is defined as a fall in FEV1 from pre-challenge of ≥ 20% with standard doses of methacholine or ≥ 15% with standardised hyperventilation, hypertonic saline, or mannitol challenge, or (e) Positive exercise challenge test within 5 years prior to Visit 1. A positive test is defined as a fall in FEV1 of > 10% and > 200 mL from pre-challenge, or (f) Significant increase in lung function after 4 weeks of anti-inflammatory treatment with ICS-containing treatment (GINA 2023) within 5 years prior to Visit 1, defined as an increase in FEV1 > 12% and 200 mL (or PEF by >20%)"}
• {"criterion_text":"- Treated with medium- or high-dose ICS (as per GINA 2023) in combination with LABA (GINA Step 4 or 5 therapy); the dose of ICS must be stable for at least 30 days prior to Visit 1. The ICS can be contained within an ICS-LABA fixed-dose combination product. Note: Treatment with additional asthma controller therapies (eg, LAMA) at a stable dose ≥ 30 days prior to Visit 1 is allowed."}
• {"criterion_text":"- Demonstration of uncontrolled asthma through ACQ-6 score ≥ 1.5 at both Visit 1 and Visit 2."}

Exclusion criteria

• {"criterion_text":"- Life-threatening asthma defined as a history of significant asthma episode(s) involving intubation, respiratory arrest, hypoxic seizures, or asthma-related syncopal episode(s)."}
• {"criterion_text":"- Patients with recent myocardial infarction, unstable angina pectoris, stroke, or percutaneous coronary intervention within 3 months of Visit 1 or coronary artery bypass grafting within 6 months of Visit 1."}
• {"criterion_text":"- A helminth parasitic infection diagnosed within 24 weeks of Visit 1 that has not been treated, or has not responded to SoC therapy."}
• {"criterion_text":"- Current smokers, former smokers with > 10 pack-years history, or former smokers who stopped smoking < 6 months before Visit 1 (including all forms of tobacco, e-cigarettes [vaping], and other recreational drugs including marijuana)."}
• {"criterion_text":"- Known history of drug or alcohol abuse within the 12 months prior to Visit 1, that in the Investigator’s opinion would preclude participation in the study. The use of oral cannabis is permitted."}
• {"criterion_text":"- Current diagnosis of cancer or unresectable cancer that has not been in complete remission for at least 5 years prior to Visit 1. Note: Squamous cell and basal cell carcinomas of the skin and cervical carcinoma-in-situ that have been treated and considered cured at the time of enrolment are not exclusionary."}
• {"criterion_text":"- Any other clinically relevant abnormal findings on vital signs, physical examination, or clinical laboratory testing including haematology, coagulation, clinical chemistry, or ECG between Visit 1 and Visit 2, that in the opinion of the Investigator or medical monitor might compromise the safety of the patient in the study or interfere with evaluation of the study intervention. Abnormal findings include, but are not limited to: (a) ALT or AST > 2 × ULN (b) TBL > 1.5 × ULN (unless due to Gilbert’s disease) Treatment with any of the following therapeutic interventions within the specified time before Visit 1"}
• {"criterion_text":"- Treatment with marketed or investigational biologics for asthma or immunological disease within 4 months or a minimum of 5 half-lives, prior to Visit 1, whichever is longer."}
• {"criterion_text":"- Systemic steroids within 4 weeks prior to Visit 1."}
• {"criterion_text":"- Chronic oral or systemic CS use for asthma or for any other indication (with the exception of stable replacement therapy in adrenal insufficiency)."}
• {"criterion_text":"- Completed treatment for respiratory infection and/or asthma exacerbation with systemic corticosteroids and/or antibiotics for > 3 days in the 4 weeks prior to Visit 1."}
• {"criterion_text":"- Clinically important pulmonary disease other than asthma; including but not limited to those with co-existent chronic obstructive pulmonary disease."}
• {"criterion_text":"- Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric, or major physical impairment that is not stable in the opinion of the Investigator and could: (a) Affect the safety of the patient throughout the study (b) Influence the findings of the study or their interpretation (c) Impede the patient’s ability to complete the entire duration of study"}
• {"criterion_text":"- Patients who, in the opinion of the Investigator, have evidence of active TB or are currently on treatment for active or latent TB. Investigation for active or latent TB, with interferon gamma release assay (IGRA) and/or chest X-ray, should only be considered if deemed clinically indicated by the Principal Investigator."}
• {"criterion_text":"- Medical history of or treatment for hepatitis B or hepatitis C, except for cured hepatitis C, as defined by: (a) Positive test for HBsAg (b) Positive test for anti-HBc: Patients who test positive for anti-HBc antibody but negative for HBsAg may be enrolled if their hepatitis B virus DNA test result is negative (c) Positive test for anti-hepatitis C antibody: Patients who test positive for antihepatitis C antibody may be enrolled if their hepatitis C viral RNA test result is negative in the absence of liver cirrhosis"}
• {"criterion_text":"- Patients with history of HIV infection or who test positive for HIV."}
• {"criterion_text":"- Congenital long QT syndrome or prolonged QTcF > 470 ms or history of QT prolongation associated with other medications that required discontinuation of that medication."}
• {"criterion_text":"- Current untreated or uncontrolled arrhythmia (eg, multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia). Note: Patients with clinically significant sinus nodal disease/bradycardia or type 2 second- or third-degree atrioventricular block can be included if treated with a pacemaker"}

Primary endpoints

• {"endpoint_text":"- Time to first CompEx Asthma event","definition_or_measurement_approach":"Primary endpoint as stated: time to first CompEx Asthma event. No further definition or measurement approach is provided in the available fields."}

Secondary endpoints

• {"endpoint_text":"- To evaluate the effect of AZD8630 as compared to placebo on lung function: Change from baseline to: Measured in the clinic: 1 Pre-BD FEV1 2 Post-BD FEV1 3 Pre-BD FEF25-75 4 Pre-BD FVC 5 Post-BD FVC Measured in the home 6. PEF: Weeks 1, 2, 4, 6, 8, 7. maximum pre-BD","definition_or_measurement_approach":"Change from baseline measured in clinic (pre- and post-bronchodilator spirometry measures FEV1, FEF25-75, FVC) and at home PEF at specified weeks and maximum pre-BD values."}
• {"endpoint_text":"- To evaluate the effect of AZD8630 as compared to placebo on asthma symptoms, asthma control and quality of life Change from baseline to: 1 Weekly mean asthma symptom diary score: 2 ACQ-6 3 AQLQ+12 4 SGRQ 5 SNOT-22 (for patients with chronic rhinosinusitis with nasal polyposis)","definition_or_measurement_approach":"Change from baseline assessed by weekly mean asthma symptom diary, ACQ-6, AQLQ+12, SGRQ, and SNOT-22 (for relevant patients)."}
• {"endpoint_text":"- To evaluate the effect of AZD8630 as compared with placebo on asthma-related biomarkers Change from baseline to: 1 FeNO 2 Blood eosinophils 3 Total IgE","definition_or_measurement_approach":"Change from baseline in biomarkers: fractional exhaled nitric oxide (FeNO), blood eosinophil count, and total IgE."}
• {"endpoint_text":"- To evaluate the pharmacokinetics (PK) of AZD8630 and ADA AZD8630 serum concentrations and ADA (incidence and titres).","definition_or_measurement_approach":"Measurement of AZD8630 serum concentrations and assessment of anti-drug antibodies (ADA) incidence and titres."}

Methods

• Posters (language- and country-specific posters are listed in recruitment documents for Belgium and other countries)
• Pamphlets (country/language-specific patient pamphlets listed)
• Social media images (documents listed: 'Social Media Images' in multiple languages)
• Website recruitment pages (documents listed: 'Website' materials in multiple languages)
• Local advertisement materials (K1/K2 local advertisement PDFs referenced)
• Recruitment plan provided by Meclinas (document: 'Meclinas_Recruitment Plan')

Belgium

Earliest CTIS Part Ii Submission Date

13-11-2024

Latest Decision Or Authorization Date

24-07-2025

Processing Time Days

253

Number Of Sites

3

Number Of Participants

5

Czechia

Earliest CTIS Part Ii Submission Date

15-11-2024

Latest Decision Or Authorization Date

13-08-2025

Processing Time Days

271

Number Of Sites

8

Number Of Participants

20

Denmark

Earliest CTIS Part Ii Submission Date

27-11-2024

Latest Decision Or Authorization Date

15-08-2025

Processing Time Days

261

Number Of Sites

7

Number Of Participants

20

Germany

Earliest CTIS Part Ii Submission Date

19-11-2024

Latest Decision Or Authorization Date

04-09-2025

Processing Time Days

289

Number Of Sites

9

Number Of Participants

15

Netherlands

Earliest CTIS Part Ii Submission Date

28-11-2024

Latest Decision Or Authorization Date

24-07-2025

Processing Time Days

238

Number Of Sites

2

Number Of Participants

5

Slovakia

Earliest CTIS Part Ii Submission Date

14-11-2024

Latest Decision Or Authorization Date

04-08-2025

Processing Time Days

263

Number Of Sites

7

Number Of Participants

12

Italy

Earliest CTIS Part Ii Submission Date

19-11-2024

Latest Decision Or Authorization Date

17-08-2025

Processing Time Days

271

Number Of Sites

4

Number Of Participants

8

Spain

Earliest CTIS Part Ii Submission Date

19-11-2024

Latest Decision Or Authorization Date

13-10-2025

Processing Time Days

328

Number Of Sites

8

Number Of Participants

15

France

Earliest CTIS Part Ii Submission Date

18-11-2024

Latest Decision Or Authorization Date

16-01-2026

Processing Time Days

424

Number Of Sites

5

Number Of Participants

10

Primary sponsor

Full Name

AstraZeneca AB

Organisation Type

Pharmaceutical company

Country Of Registered Address

Sweden