A Randomized, DBPC Study to Determine the Safety, Tolerability and Immunological Effects of BM41 Compared to Placebo and to Treatment With Standard s.c. Immunotherapy in Patients Allergic to Birch Pollen
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 47
- 试验地点
- 1
- 主要终点
- Incidence of adverse events with emphasis on allergic reactions. Safety/tolerability of subcutaneous treatment with BM41 compared to placebo (double-blind) and to a conventional standardized birch pollen extract in patients with birch pollen allergy
研究概览
简要总结
The aim of this clinical phase I single centre, randomized, double-blind, placebo-controlled study with open comparator is to investigate tolerability and safety as well as the immunological effects of BM41 in comparison to placebo (double blind) and to a standard subcutaneous immunotherapy Alutard SQ (open) in birch allergic patients.
详细描述
Please see original article.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent
- •Age ≥18 ≤ 65 years
- •Moderate to severe birch-pollen-induced allergic rhinitis/rhinoconjunctivitis of at least 2 years according to the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines (Appendix 1, see the manual of procedures) with or without concomitant mild to moderate persistent asthma
- •Forced expiratory volume (FEV1) >70% for patients with a history of asthma, FEV1>70% or peak flow (PEF) >80% for patients without a history of asthma
- •A positive skin prick test (SPT) (mean wheal diameter ≥ 3mm compared to negative control and negative control should be negative) for birch pollen assessed within 1 year before randomization
- •Specific IgE against birch pollen extract ≥ 0.7 kU/L and against Bet v 1 ≥ 0.35 kU/L as determined by ImmunoCAP
排除标准
- •Chronic asthma with an FEV1<70 % of predicted value.
- •History of allergen immunotherapy (AIT) (subcutaneous (SCIT) or sublingual (SLIT)) with birch pollen or tree pollen mix including birch pollen within the past 5 years
- •Ongoing AIT (SCIT or SLIT) with any allergen(s) during the study period
- •Vaccination within one week before or during the treatment phase.
- •Immunosuppressive or biological medication (e.g. IL-5, anti-IgE therapy) within the last six months prior to inclusion and up to end of trial (EoT).
- •Severe immune disorders (including auto-immune diseases) and/or diseases requiring immunosuppressive drugs.
- •Uncontrolled asthma or other active respiratory diseases.
- •Active malignancies or any malignant disease during the previous 5 years.
- •Severe uncontrolled diseases that could increase the risk for patients participating in the study, including but not limited to: cardiovascular insufficiency, any severe or unstable lung diseases, endocrine diseases, clinically significant renal or hepatic diseases, or haematological disorders.
- •Renal insufficiency
- •Active inflammation or infection of the target organs (nose, eyes or lower airways) at the start of the study.
- •Diseases with a contraindication for the use of adrenaline (e.g. hyperthyroidism, glaucoma).
- •Use of systemic steroids within 4 weeks before start of the study and during the study.
- •Treatment with systemic and local β-blockers.
- •Known allergy towards constituents of the vaccine
- •Pregnancy, lactation or inadequate contraceptive measures for women of child-bearing age (adequate contraceptive measures will be intrauterine device or hormonal contraception (birth control pill, implant, transdermal patch, vaginal ring or depot injection). It is also accepted, if the female patient is permanently sterile or infertile, if her sole partner is permanently sterile, or if they use both condom and diaphragm, The definition of sterile or infertile is surgically sterilized (vasectomy/bilateral salpingectomy, hysterectomy and/or bilateral ovariectomy) or post menopause defined as a non-menstrual period of at least 12 months before inclusion in the study.
- •Alcohol, drug or medication abuse within the past year.
- •Any clinically significant abnormal laboratory parameter at screening.
- •Lack of cooperation or compliance.
- •Any physical or mental condition that precludes administration of SCIT, compliance or participation in a clinical trial.
- •Patients who are students or employees of the institution or 1st grade relatives or partners of the investigators
- •Participation in a clinical trial within 3 months prior to the current trial.
研究组 & 干预措施
BM41
9 treatment visits where subcutaneous injections with solution of the test drug BM41 (adsorbed to aluminium hydroxide) in a blinded fashion starting with 12.5 nanogram increasing to 20 microgram which is maintenance dose. Subsequently 3 maintenance doses will be given.
Please look at the results in the original article.
干预措施: BM41 (Drug)
Placebo
Placebo consisting of only aluminium hydroxide will be administered blinded in amounts according to BM41.
干预措施: Placebo (Other)
Alutard
Alutard SQ (ALK) will serve as the comparator and administration is open. Up-dosing is performed according to the official cluster scheme, reaching maintenance of 100.000 SQ-E
干预措施: ALK Alutard SQ Betula verrucosa (Drug)
结局指标
主要结局
Incidence of adverse events with emphasis on allergic reactions. Safety/tolerability of subcutaneous treatment with BM41 compared to placebo (double-blind) and to a conventional standardized birch pollen extract in patients with birch pollen allergy
时间窗: Through study completion, an average of 4 months
Safety/tolerability of subcutaneous treatment with BM41 compared to placebo (double-blind) and to a conventional standardized birch pollen extract. Number and character of all adverse events will be evaluated.
次要结局
- Changes in serum immunoglobulin E (IgE), immunoglobulin G (IgG) and immunoglobulin G4 (IgG4) levels.(Day 7, 42 and 126)
- Changes in the capacity to block IgE facilitated allergen binding and histamine release.(Day 7, 42 and 126)
- Changes in wheal sizes upon titrated skin prick test with BM41.(Day 7, 42 and 112)
- Epigenetic changes induced by BM41 and Alutard compared to placebo(Day 7, 42 and 126)
研究者
Carsten Bindslev-Jensen
Professor
Odense University Hospital