CTRI/2022/03/040954招募中3 期
A Phase III, Multicentre, Randomised, Double-blind, Chronic-dosing, Parallel-group, Placebo-controlled Study to Evaluate the Efficacy and Safety of Two Dose Regimens of MEDI3506 in Participants with Symptomatic Chronic Obstructive Pulmonary Disease (COPD) with a History of COPD Exacerbations - OBERON Study
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 1,272
- 试验地点
- 15
- 主要终点
- To evaluate the effect of 2 dose regimens of MEDI3506 as add on to SoC compared with SoC plus placebo on the rate of moderate to severe COPD exacerbations in former smokers
研究概览
简要总结
Phase III, multicentre, randomised, double-blind, chronic-dosing, parallel-group,
placebo-controlled study to evaluate the efficacy and safety of MEDI3506 Q8W and Q4W administered SC, in adult participants with symptomatic COPD and history of COPD exacerbations.
The primary and secondary objectives:
To evaluate the effect of 2 dose regimens of MEDI3506 as add on to SoC compared with SoC plus placebo on the rate of moderate to severe COPD exacerbations in former smokers.
To evaluate the effect of 2 dose regimens of MEDI3506 as add on to SoC compared with SoC plus placebo on the rate of moderate to severe COPD exacerbation in former and current smokers.
To evaluate the effect of 2 dose regimens of MEDI3506 as add on to SoC compared with SoC plus placebo on time to moderate to severe COPD exacerbations.
A total of 1272 participants will be randomized 1:1:1 to receive two dose regimen of MEDI 3506 or placebo and includes:
I. Screening Period: Up to 2 weeks
a. Treatment Period: 48-weeks double-blind treatment period with:
II. Study intervention administration (MEDI3506 or placebo) SC Q4W , Q8W from Week 0 to Week 48 for a total of 14 doses
Follow-up Period: Up to 8 weeks after last efficacy assessment at Week 52 (ie, 12 weeks after last dose of study intervention)
研究设计
- 研究类型
- Interventional
- 分配方式
- Stratified randomization
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 40.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Inclusion Criteria 1 Participant must be ≥ 40 years of age at the time of signing the ICF.
- •2 Documented diagnosis of COPD for at least one year prior to enrolment.
- •3 Post-BD FEV1/FVC < 0.70 and post-BD FEV1 >20% of predicted normal value (as assessed by central spirometry at screening).
- •4 Documented history of ≥ 2 moderate or ≥ 1 severe COPD exacerbations within 12 months prior to enrolment: (a) An exacerbation is considered moderate if it required treatment with systemic corticosteroids and/or antibiotics, and severe if it required hospitalization.
- •Note: hospitalization is defined as an inpatient admission ≥ 24 hours in the hospital, in an observation area, emergency department, or other equivalent healthcare facility depending on the country and healthcare system.
- •(b) At least one qualifying exacerbation should have been treated with systemic corticosteroids.
- •(c) Events treated with antibiotics alone qualify as a moderate exacerbation only when antibiotic was specifically prescribed for worsening of COPD symptoms.
- •(d) Previous exacerbations should be confirmed to have occurred while the participant was on stable dual or triple (ICS/LABA/LAMA) maintenance inhaled therapy for COPD and not as a result of a gap or step down in the treatment.
- •(e) At least one qualifying exacerbation should have occurred while on the most recent stable uninterrupted therapy prior to enrolment.
- •Documented optimised treatment with COPD inhaled maintenance therapy (ICS/LABA/LAMA triple therapy, or dual therapy if triple is not indicated or contraindicated) and at a stable dose for at least 3 months prior to enrolment.
- •During this period: (a) Individual component changes or switches between devices are allowed as long as the participant remains on the same class therapies in equivalent doses (b) Short-term changes in background treatment regimen during COPD exacerbation are acceptable.
- •(c) Short-acting muscarinic antagonist taken at regular scheduled interval (at a minimum frequency of 3 times daily) will be considered equivalent to LAMA.
- •(d) If participant is being treated with any oral COPD maintenance therapy (eg, macrolides, xanthines, roflumilast), these treatments must also be stable for at least 3 months prior to enrolment.
- •6 Smoking history of ≥ 10 pack-years: (a) Former smokers will be defined as participants who are currently not smoking and with smoking cessation ≥ 6 months prior to screening with an intention to quit permanently.
- •(b) Current smokers will be defined as participants who are currently smoking tobacco (at least one cigarette per day on average during the past 7 days) and are not currently participating in smoking cessation.
- •(c) Electronic cigarette (e-cigarette) use does not contribute to the pack-year count for eligibility.
- •7 CAT total score ≥ 10, with each of the phlegm (sputum) and cough items with a score ≥ 2, at both screening (V1) and randomisation (V2).
- •8 At least 70% daily PRO completion during the entire screening period, with at least 50% daily PRO completion in the 14-day period prior to randomisation.
- •9 At least 70% compliance with COPD maintenance inhaled therapy (defined as taking COPD maintenance inhaled medication as scheduled for the day) during the entire screening period.
- •10 Able to read and use electronic devices.
- •11 Female participants of childbearing potential must have a negative serum pregnancy test at V1 and a negative urine pregnancy test at V
- •12 Contraceptive use by males and females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- •a) Male participants: • Non-sterile 2 male participants who are sexually active with a female partner of childbearing potential must agree to use a male condom while engaging in sexual activity from enrolment throughout the study duration and until 14 weeks after last dose of IP.
- •In countries where spermicide is available, it is strongly recommended.
- •â€¢ Non-sterilised male patients should also refrain from biologically fathering a child or donating sperm during the same period.
- •b) Female participants: • Females not of childbearing potential are defined as females who are either permanently sterilised (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal.
- •Females will be considered postmenopausal if they have been amenorrhoeic for 12 months prior to the planned date of randomisation without an alternative medical cause.
- •The following age-specific requirements apply: Females < 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatment and follicle stimulating hormone (FSH) levels in the postmenopausal range.
- •â€¢ Females of childbearing potential who are sexually active with a non-sterilised male partner must agree to use one highly effective method of birth control, as defined below, from enrolment throughout the study and until at least 14 weeks after last dose of IP.
- •Cessation of contraception after this point should be discussed with a responsible physician.
- •Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea method are not acceptable methods of contraception.
- •Female condom and male condom should not be used together.
- •â€¢ A highly effective method of contraception is defined as one that can achieve a failure rate of less than 1% per year when used consistently and correctly.
- •Highly effective birth control methods include: sexual abstinence (periodic abstinence eg, calendar, ovulation, symptothermal, post-ovulation methods, declaration of abstinence for the duration of exposure to IP, and withdrawal are not acceptable methods of contraception), a vasectomised partner, Implanon®, bilateral tubal occlusion, intrauterine device/levonorgestrel intrauterine system, Depo-Proveraâ„¢ injections, oral contraceptive, and Evra Patchâ„¢, Xulaneâ„¢, or NuvaRing®.
- •It is highly recommended for the male partner of a female participant who is of childbearing potential to use a male condom whilst engaging in sexual activity throughout this period.
- •â€¢ Note there are no contraception requirements for female participants who are not of childbearing potential.
- •13 Capable of giving signed informed consent as described in Appendix A which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
- •14 Provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of samples for optional genetic research that supports Genomic Initiative.
排除标准
- •Clinically important pulmonary disease other than COPD (eg, active lung infection, clinically significant bronchiectasis, pulmonary fibrosis, cystic fibrosis, hypoventilation syndrome associated with obesity, lung cancer, alpha 1 anti-trypsin deficiency, and primary ciliary dyskinesia).
- •Radiological findings suggestive of a respiratory disease other than COPD that is contributing to the participant s respiratory symptoms.
- •Radiological findings of solitary pulmonary nodules without appropriate follow up and demonstration of stability as per standard of care, or findings suggestive of acute infection.
- •3 Current diagnosis of asthma according to the GINA or other accepted guidelines, prior history of asthma, or asthma-COPD overlap
- •Childhood history of asthma is allowed and defined as asthma diagnosed and resolved (ie, not requiring the use of any maintenance or rescue medication) before the age of
- •4 Any unstable disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric disorder, major physical and/or cognitive impairment that, in the opinion of the investigator, could: (a) Affect the safety of the participant throughout the study.
- •(b) Influence the findings of the study or their interpretation.
- •(c) Impede the participant s ability to complete the entire duration of the study and/or comply with the study visit schedule and procedures.
- •5 COPD exacerbation, within 2 weeks prior to randomisation, that was treated with systemic corticosteroids and/or antibiotics, and/or led to hospitalisation (based on last dose of corticosteroids or antibiotics, or last date of hospitalisation, whichever occurred later).
- •6 Active significant infection (viral, bacterial, or fungal infections requiring treatment with systemic antibiotic, antiviral, or antifungal medication, respectively) within the 4 weeks prior to randomisation, pneumonia within 6 weeks prior to randomisation, or medical condition that predisposes the participant to infection.
- •7 Suspicion of, or confirmed, ongoing SARS-CoV-2 infection.
- •8 Significant COVID-19 illness within the 6 months prior to enrolment, defined as: (a) A diagnosis of COVID-19 pneumonia based on radiological assessment.
- •(b) A diagnosis of COVID-19 with significant new findings from pulmonary imaging tests.
- •(c) A diagnosis of COVID-19 requiring hospitalisation and/or oxygen supplementation therapy.
- •9 Unstable cardiovascular disorder (including but not limited to: ischaemic heart disease, arrhythmia, cardiomyopathy, unstable moderate to severe heart failure (NYHA class III-IV and or LVEF < 30%), clinically significant aortic stenosis, uncontrolled arterial hypertension, or any other relevant cardiovascular condition), that, in the investigator s judgement may put the participant at risk or negatively affect the outcome of the study.
- •Diagnosis of cor pulmonale, pulmonary arterial hypertension and/or right ventricular failure.
- •11 History of active severe inflammatory bowel disease or colitis within one year prior to enrolment, or unexplained diarrhoea within the 4 weeks prior to randomisation.
- •12 History of known immunodeficiency disorder, including a positive test for HIV-1 or HIV-
- •13 History of positive test or treatment for hepatitis B or hepatitis C.
- •For hepatitis B testing, any of the following would exclude the participant from the study: (a) Positive test for HBsAg. (b) Positive test for anti-HBc. Note: participants with a history of hepatitis B vaccination without a history of hepatitis B are permitted.
- •Note: transient increase of ALT/AST/TBL level that resolves by the time of randomisation is acceptable if, in the investigator s opinion, the participant does not have active liver disease and meets other eligibility criteria.
- •15 Malignancy, current or within the past 5 years, except for adequately treated non-invasive basal cell and squamous cell carcinoma of the skin and cervical carcinoma-in-situ treated with apparent success more than one year prior to enrolment.
- •Suspected malignancy or undefined neoplasms.
- •16 Participants who, in the opinion of the investigator or qualified designee, have evidence of active TB.
- •Participants with a recent (within 2 years) first-time or newly positive purified protein derivative (PPD) test or QuantiFERON-TB (QFT) test need to complete an appropriate course of treatment before being considered for enrolment.
- •Evaluation will be according to the local standard of care and may consist of history and physical examinations, chest X-ray, and/or TB test as determined by local guidelines 17 History of partial or total lung resection (single lobe or segmentectomy is acceptable).
- •Surgical or endoscopic (eg, valves) lung volume reduction within the 6 months prior to enrolment.
- •Expected need for lung volume reduction surgery during the study.
- •18 Scheduled major surgical procedure during the course of the study.
- •Minor elective procedures are allowed.
- •19 Treatment with systemic corticosteroids or other immunosuppressive medication within 2 weeks prior to randomisation.
- •20 Long-term oxygen therapy (LTOT) > 4.0 L/min.
- •While breathing supplemental oxygen, participants should demonstrate an oxyhaemoglobin saturation ≥ 89%.
- •In order to be admitted to the study, participants on long-term oxygen therapy have to be ambulatory and able to attend clinic visits.
- •21 Participants with use, or need for chronic use, of any non-invasive positive pressure ventilation device.
- •Participants using continuous positive airway pressure for sleep apnoea syndrome are permitted in the study.
- •22 Participation in, or scheduled for, an intensive (active) COPD rehabilitation program (participants who are in the maintenance phase of a rehabilitation program are eligible to take part).
- •23 Receipt of blood products or immunoglobulins within 30 days prior to randomisation.
- •24 Receipt of live attenuated vaccines within 30 days prior to randomisation.
- •25 Chronic use of immunosuppressive medication at screening and/or randomisation (including but not limited to: methotrexate, troleandomycin, cyclosporine, azathioprine, rectal corticosteroids, and systemic corticosteroids), or expected need for chronic use during the study.
- •26 Chronic use of antibiotics if the duration of treatment is < 3 months prior to enrolment.
- •Chronic macrolide or other antibiotic therapy is allowed provided the participant has been on a stable dose/regimen for ≥ 3 months prior to enrolment and has had at least one COPD exacerbation while on stable therapy.
- •27 Use of allergen immunotherapy within 3 months of randomisation, except for stable maintenance dose allergen-specific immunotherapy started 4 weeks prior to V
- •28 Use of interferon gamma within 3 months of randomisation.
- •29 Receipt of any marketed or investigational biologic product for any reason within 4 months or 5 half-lives prior to randomisation, whichever is longer.
- •30 Participation in any interventional clinical trial or receipt of any investigational nonbiologic product within 30 days or 5 half-lives prior to randomisation, whichever is longer.
- •31 Participants that have previously received MEDI3506 32 Known history of: a) Severe allergic reaction to a systemic monoclonal antibody b) Allergy or reaction to any component of the IP formulation.
结局指标
主要结局
To evaluate the effect of 2 dose regimens of MEDI3506 as add on to SoC compared with SoC plus placebo on the rate of moderate to severe COPD exacerbations in former smokers
时间窗: week 52
次要结局
- To evaluate the effect of 2 dose regimens of MEDI3506 as add on to SoC compared with SoC plus placebo on change in pre-BD lung function(week 52)
- To evaluate the effect of 2 dose regimens of MEDI3506 as add on to SoC compared with SoC plus placebo on respiratory symptoms(week 52)
- To evaluate the effect of 2 dose regimens of MEDI3506 as add on to SoC compared with SoC plus placebo on the rate of moderate to severe COPD exacerbation in former and current smokers(week 52)
- To evaluate the effect of 2 dose regimens of MEDI3506 as add on to SoC compared with SoC plus placebo on time to moderate to severe COPD(exacerbations)
- To evaluate the effect of 2 dose regimens of MEDI3506 as add on to SoC compared with SoC plus placebo on respiratory health status/health-related quality of life.(Week 52)
- To evaluate the effect of 2 dose regimens of MEDI3506 as add on to SoC compared with SoC plus placebo on severe COPD exacerbations(Week 52)
- To further evaluate the effect of 2 dose regimens of MEDI3506 as add on to SoC compared with SoC plus placebo on COPD health status/health-related quality of life(week 52)
- To evaluate the effect of 2 dose regimens of MEDI3506 as add on to SoC compared with SoC plus placebo on overall and COPD-related HRU(Week 52)
- To evaluate the effect of 2 dose regimens of MEDI3506 as add on to SoC compared with SoC plus placebo on daily rescue medication use over(week 52)
- To evaluate the pharmacokinetics and immunogenicity of 2 dose regimens of MEDI3506 over(52 weeks)
- To assess the safety and tolerability of 2 dose regimens of MEDI3506 as add on to SoC compared with SoC plus placebo(Week 52)
研究者
研究点 (15)
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