E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Obstructive Pulmonary Disease (COPD) |
Chronische Obstructieve Longziekte (COL) |
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E.1.1.1 | Medical condition in easily understood language |
COPD is a chronic lung disease that causes increasing airflow obstruction in the lungs, resulting in breathlessness and cough, and in some people causing disease flares or exacerbations. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10077773 |
E.1.2 | Term | Chronic obstructive pulmonary disease exacerbation |
E.1.2 | System Organ Class | 100000004855 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the effect of astegolimab compared with placebo, on annualized rate of moderate and severe acute exacerbations of COPD over 52 weeks of treatment |
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E.2.2 | Secondary objectives of the trial |
•To evaluate the effect of astegolimab compared with placebo on time to first moderate or severe COPD exacerbation •To evaluate the effect of astegolimab compared with placebo on St George’s Respiratory Questionnaire •To evaluate the effect of astegolimab compared with placebo on post-bronchodilator forced expiratory volume in 1 second (FEV1) •To evaluate the effect of astegolimab compared with placebo on Evaluating Respiratory Symptoms in COPD (E-RS:COPD) •To evaluate the effect of astegolimab compared with placebo on annualized rate of severe COPD exacerbations •To evaluate the effects of astegolimab compared with placebo on safety |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Signed Informed Consent Form •Age 40-90 years at time of signing Informed Consent Form •Ability to comply with the study protocol •Documented physician diagnosis of COPD made at least 12 months prior to screening •History of frequent exacerbations, defined as having had two or more moderate or severe exacerbations occurring within a 12-month period in the 24 months prior to screening. Exacerbations should have been treated with systemic corticosteroids and/or antibiotics. A moderate COPD exacerbation is defined as new or increased COPD symptoms (e.g., dyspnea, sputum volume, and sputum purulence) that lead to treatment (duration => 3 days) with systemic corticosteroids (oral, IV, or IM) at a dose of >10 mg/day prednisolone equivalent and/or antibiotics. Prior use of antibiotics alone does not qualify as a moderate exacerbation, unless the use was specifically for the treatment of worsening symptoms of COPD. A severe COPD exacerbation is defined as new or increased COPD symptoms that lead to hospitalization (duration >24 hours) or lead to or death. •Post-bronchodilator FEV1 =>20 and <80% of predicted normal value at screening, as verified by over-reader •Post-bronchodilator FEV1/FVC < 0.70 at screening, as verified by over-reader •mMRC score => 2 at screening •Current smoker or former smoker with a minimum of 10 pack-year history (e.g., 20 cigarettes/day for 10 years) A former smoker is defined as meeting the criteria above but has not used inhaled tobacco products or inhaled marijuana within 6 months prior to screening, through use of cigarettes, cigars, electronic cigarettes, vaporizing devices, or pipe. Note that at screening, patients who meet the protocol definition of current smoker will receive smoking cessation counseling. •History of one of the following combinations of optimized, stable, standard-of-care COPD maintenance therapy for at least 4 weeks prior to screening, with no anticipated changes in therapy prior to initiation of study drug and throughout the study: Inhaled corticosteroid (ICS) => 500 mcg/day fluticasone propionate dose-equivalent plus long-acting beta-agonist (LABA). – Long-acting muscarinic antagonist (LAMA) plus LABA. – ICS => 500 mcg/day fluticasone propionate dose-equivalent plus LAMA plus LABA •Demonstrated ability to use and comply with electronic diary (eDiary) requirements, defined as completion of all questions on at least 5 out of 7 consecutive days within the 14 days after the screening visit Patients unable to demonstrate compliance with the eDiary within the first 2 weeks of screening will be screen failed. Patients will have the opportunity to demonstrate eDiary compliance if re-screened. •For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, as defined below: Women must remain abstinent or use contraceptive methods with a failure rate of <1% per year during the treatment period and for 12 weeks after the final dose of Astegolimab. A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (=> 12 continuous months of amenorrhea with no identified cause other than menopause), and is not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the investigator (e.g., Müllerian agenesis). The definition of childbearing potential may be adapted for alignment with local guidelines or regulations. Examples of contraceptive methods with a failure rate of <1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception. If required per local guidelines or regulations, locally recognized adequate methods of contraception and information about the reliability of abstinence will be described in the local Informed Consent Form. •For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, as defined below: With a female partner of childbearing potential or pregnant female partner, men must remain abstinent or use a condom during the treatment period and for 12 weeks after the final dose of Astegolimab to avoid exposing the embryo. Men must refrain from donating sperm during this same period. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence. |
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E.4 | Principal exclusion criteria |
Pregnant or breastfeeding, or intending to become pregnant during the study or within 12 weeks after the final dose of study drug. Women of childbearing potential must have a negative serum pregnancy test result at screening and a negative urine pregnancy test on Day 1 prior to initiation of study drug. •Current documented diagnosis of asthma according to the Global Initiative for Asthma guidelines or other accepted guidelines within 5 years prior to screening •History of clinically significant pulmonary disease other than COPD (e.g., pulmonary, fibrosis, sarcoidosis, chronic pulmonary embolism or primary pulmonary hypertension, alpha-1-antitrypsin deficiency) •Clinically significant abnormalities requiring clinical follow-up as indicated by chest X-ray or chest CT scan performed within 6 months prior to screening Chest X-ray must be performed at screening if results from a chest X-ray or chest CT scan performed within 6 months prior to screening are not available. •Presence of risk factors for aspiration pneumonia (e.g., neurologic disease such as uncontrolled epilepsy) in the opinion of the investigator •History of long-term treatment with oxygen at > 4.0 liters/minute. While breathing supplemental oxygen, patient should demonstrate an oxyhemoglobin saturation of => 89%. •History of a severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of the study drug •Lung volume reduction surgery or procedure within 12 months prior to screening •Participation in or planned participation in a new pulmonary rehabilitation program within 4 weeks prior to screening and throughout the study treatment period. Patients who are in the maintenance phase of a rehabilitation program are eligible. •History of lung transplant •Occurrence of protocol-defined moderate or severe COPD exacerbation, COVID-19, upper or lower respiratory infection, pneumonia, or hospitalization of => 24 hours duration within 4 weeks prior to initiation of study drug •Any prior treatment with Astegolimab •Treatment with oral, IV, or IM corticosteroids (>10 mg/day prednisolone equivalent) within 4 weeks prior to initiation of study drug •Treatment with investigational therapy within 3 months or 5 drug-elimination half-lives (whichever is longer) prior to screening •Treatment with a licensed biologic agent (e.g., omalizumab, dupilumab, and/or anti-IL-5 therapies) within 3 months or 5 drug-elimination half-lives (whichever is longer) prior to screening •Initiation of a methylxanthine preparation, maintenance macrolide therapy, and/or PDE4 inhibitor within 4 weeks prior to screening •Initiation of or change in non-biologic immunomodulatory or immunosuppressive therapy within 3 months prior to screening •Treatment that is considered palliative (e.g., for life expectancy <12 months) •Use of any of the following treatments within 4 weeks prior to screening, or any condition that is likely to require such treatment during the course of the study, unless the treatment is deemed acceptable by the investigator, in consultation with the Medical Monitor: – Treatment with immunoglobulin or blood products. – Treatment with any live or attenuated vaccine (including any approved, live SARS-CoV-2 vaccine) within 4 weeks prior to screening or during the screening period, or anticipated need for live, attenuated vaccine during the course of the study, unless the vaccine is deemed medically necessary and no inactivated vaccine alternatives are available. •Administration of non-live SARS-CoV-2 vaccine (with full marketing authorization or temporary), including those delivered by non-replicating viral vectors, within 7 days prior to initiation of study drug •Planned surgical intervention during the study •Positive hepatitis C virus (HCV) antibody test result accompanied by a positive HCV RNA test at screening •Unacceptable test results for hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), and total hepatitis B core antibody (HBcAb) at screening, defined as meeting either of the following criteria: – Positive HBsAg test at screening. – Negative HBsAg test at screening, with negative HBsAb test accompanied by positive total HBcAb test, followed by quantitative hepatitis B virus (HBV) DNA => 20 IU/mL. Inability to perform HBV DNA test is exclusionary. Patients with a negative HBsAg test and positive HBsAb test are eligible. •Known immunodeficiency including, but not limited to, HIV infection •Known evidence of active or untreated latent tuberculosis •Substance abuse, as determined by the investigator, within 12 months prior to screening •History of malignancy within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year overall survival rate > 90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, or ductal carcinoma in situ
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E.5 End points |
E.5.1 | Primary end point(s) |
1.Annualized rate of moderate and severe COPD exacerbations over the 52-week treatment period |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Time to first moderate or severe COPD exacerbation during the 52-week treatment period 2. Absolute change from baseline in HRQoL at Week 52, as assessed through the St. George's Respiratory Questionnaire-COPD (SGRQ-C) total score 3. Proportion of patients with improvement in HRQoL, defined as a decrease from baseline of >/=4 points in SGRQ-C total score, at Week 52 4. Absolute change from baseline in post-bronchodilator FEV1 (liters) at Week 52 5. Absolute change from baseline in E-RS:COPD total score at Week 52 6. Annualized rate of severe COPD exacerbations over the 52-week treatment period 7. Incidence and severity of adverse events |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Up to Week 52 2-5. Baseline to Week 52 6. Up to Week 52 7. Up to Week 62 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity and Biomarker |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 122 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Canada |
Chile |
Hong Kong |
Israel |
Korea, Republic of |
Mexico |
New Zealand |
Peru |
South Africa |
United States |
Austria |
Belgium |
Bulgaria |
Denmark |
France |
Germany |
Netherlands |
Poland |
Romania |
Spain |
Sweden |
United Kingdom |
Czechia |
Argentina |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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last patient, last visit (LPLV) |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |