GB001 in adult subjects with moderate to severe asthma

Phase 1

• Conditions: Eosinophilic Asthma; MedDRA version: 21.1Level: LLTClassification code 10068462Term: Eosinophilic asthmaSystem Organ Class: 100000004855; Therapeutic area: Body processes [G] - Circulatory and Respiratory Physiological Phenomena [G09]

• Registration Number: EUCTR2018-002242-36-GB
• Lead Sponsor: GB001, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-12-11
• Last Update Posted: 19 October 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 480

Inclusion Criteria

1. Informed Consent: Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
2. Age: = 18 and < 75 years of age at the time of Screening Visit.
3. Gender: Males or females:
a. Women of childbearing potential (WOCBP) must use an acceptable method of contraception (see Appendix 4, Section 10.4 of the protocol) at least 1 month prior to Screening through 28 days after the last dose of IP.
4. Weight: at least 40 kg.
5. Diagnosis of asthma: A diagnosis of asthma by a physician according to GINA guidelines of at least 12 months prior to Screening.
6. ICS plus additional controller: Subjects with a documented requirement for regular treatment with medium or high dose ICS and at least one other controller medication for at least 12 months prior to Visit 1. Subjects must maintain a stable ICS dose regimen during the 4 weeks prior to Visit 1.
a. Medium dose ICS is defined as an ICS dose equivalent to fluticasone propionate > 250 to 500 mcg/day and high dose is defined as an ICS dose equivalent to fluticasone propionate >500mcg/day (for equivalent ICS doses see Appendix 10, Section 10.10 of the protocol)
b. An additional controller medication such as LABA, long-acting muscarinic antagonist (LAMA), or leukotriene receptor antagonist (LTRA)
7. FEV1: a pre-bronchodilator FEV1 of = 85% of predicted normal.
8. Reversibility/Airway Hyperresponsiveness: of at least 12% in FEV1 following 4 puffs of albuterol 400 µg ex-US (360 µg US) or 1 equivalent nebulized dose/salbutamol
100 mcg at Screening. Reversibility is to be assessed in all subjects at Screening.
• If a subject does not reverse at least 12% at Screening, the site may
submit historical documentation of one of the following for review and
approval by the medical monitor:
- reversibility in the 24 months prior to Screening visit, OR
- airway hyperresponsiveness demonstrated by a positive methacholine,
histamine, or mannitol challenge
If not met, historical documentation of reversibility in the 12 months prior to Screening Visit may be allowed upon review and approval by the medical monitor.
9. Evidence of uncontrolled asthma: demonstration of uncontrolled asthma by one of the following:
a. Previously confirmed history of 2 or more asthma exacerbations requiring treatment with systemic corticosteroids in the 12 months prior to Screening Visit.
OR
b. Previously confirmed history of 1 asthma exacerbation requiring treatment with systemic corticosteroids in the 12 months prior to Screening Visit and ACQ-5 of = 1.5 at Screening Visit.
10. Are willing and able to comply with the requirements for participation in the study.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 415
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 65

Exclusion Criteria

1. Smoking history: Current smokers (any substance), or former smokers with a smoking history of = 10 pack-years [(number of cigarettes per day/20) x number of years smoked]. A former smoker is defined as a subject who quit smoking at least 6 months prior to Screening Visit. This includes electronic cigarettes and vaping.
2. Concurrent Respiratory Disease: Presence of a known pre-existing clinically important lung condition other than asthma. This includes current infection, active tuberculosis infection, bronchiectasis, pulmonary fibrosis, bronchopulmonary aspergillosis or diagnoses of emphysema or chronic bronchitis (chronic obstructive pulmonary disease other than asthma) or a history of lung cancer.
3. Malignancy: A current malignancy or previous history of cancer in remission for less than 5 years prior to Screening. (Subjects will not be excluded if they had localized carcinoma of the skin that was resected for cure.)
4. Liver Disease: Known pre-existing liver disorders (i.e. non-alcoholic
fatty liver disease (NALFD) or Gilbert's syndrome), or unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices or persistent jaundice), cirrhosis, or known biliary abnormalities.
5. Other Concurrent Medical Conditions: Known, pre-existing clinically significant endocrine, autoimmune, metabolic, neurological, renal (calculated creatinine clearance < 60 mL/min), gastrointestinal, hepatic, cardiovascular, hematological, or any other system abnormalities that are uncontrolled with standard treatment.
6. Eosinophilic Disease: Subjects with any other condition that could lead to elevated eosinophils such as hypereosinophilic syndrome, including eosinophilic granulomatosis with polyangiitis.
7. ECG Assessment: QTcF = 450 msec for males or QTcF = 470 msec for females at the Screening Visit. If QTcF is above the prespecified limit and
there are no other clinically significant abnormalities, the assessment can be repeated in triplicate and the three results will be averaged for eligibility.
8. Alcohol/Substance Abuse: A history or suspected history of alcohol misuse or substance abuse, including marijuana, within 12 months prior to Screening Visit.
9. Immunodeficiency: A known immunodeficiency, including that due to human immunodeficiency virus (HIV), other than that explained by systemic corticosteroid use.
10. Investigational medications: Subjects who have received treatment with an investigational medication within the past 30 days or within 5 half-lives of the medication, whichever is longer, prior to Screening Visit. (This also includes investigational formulations of marketed products.)
11. DP2 (CRTh2) antagonist studies: Participated in another DP2 (CRTh2) antagonist study in the 12 months prior to Screening Visit or known prior intolerance or inadequate response in a prior DP2 antagonist study.
12. Receiving prohibited medications or treatments: (refer to Appendix 8, Section 10.8, for more details)
a. Regular use of systemic corticosteroids or immunosuppressive therapies including methotrexate or azathioprine
b. Monoclonal antibodies used in the treatment of asthma such as reslizumab, mepolizumab, omalizumab or benralizumab
c. Medications, food or drink that are moderate or strong CYP3A4 inhibitors or inducers
d. Medications that have the potential for interaction with GB001
e. Bronchial thermoplasty and radiotherapy are excluded in the 12 month

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified