ALX-0171 Safety Study in Adults With Hyperresponsive Airways

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01909843
Recruitment Status : Completed
First Posted : July 29, 2013
Last Update Posted : January 3, 2014
Information provided by (Responsible Party):

Brief Summary:

This is a Phase I, single-centre, open label study to evaluate the occurrence and subsequent reversibility and prevention, of bronchoconstriction following single and repeated oral inhalations of ALX-0171 in adults with hyperresponsive airways.

This phase I study is an exploratory study and serves to evaluate the occurrence and reversibility of bronchoconstriction upon inhalation of ALX-0171. The study is an open label trial with a sequential administration regimen of placebo and verum in all planned study subjects. Each subject will start the treatment with a single dose of ALX-0171 placebo (= formulation buffer) followed by escalating doses of ALX-0171 verum.

Eventually a second administration of ALX-0171 placebo may take place at the end of the study (as defined per protocol).

Condition or disease Intervention/treatment Phase
Respiratory Syncytial Virus Infection Biological: ALX-0171 Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I, Single-centre, Open Label Study to Evaluate the Potential Occurrence, Reversibility and Prevention of Bronchoconstriction as Individual Response to Escalating Doses Followed by Repeated Doses of ALX-0171, Administered by Oral Inhalation to Adults With Hyperresponsive Airways
Study Start Date : August 2013
Actual Primary Completion Date : December 2013

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: ALX-0171 Oral inhalation Biological: ALX-0171
Escalating dose of ALX-0171 during maximum 3 consecutive days: from 2.1 mg to maximum 200 mg per inhaled dose followed by daily dose of 70 mg, 140 mg or 200 mg per dose for maximum 4 consecutive days

Primary Outcome Measures :
  1. Number of subjects reacting with bronchoconstriction to treatment (ALX- 0171 placebo or ALX-0171 verum) with one or more drops in forced expiratory volume in one second (FEV1) within a period of 8h post-inhalation [ Time Frame: Within a period of 8 hours post-inhalation ]

Secondary Outcome Measures :
  1. Total number of bronchoconstriction events [ Time Frame: Day 1 to Day 7 ]
  2. The frequency of use of β2-agonist for the treatment of study drug/procedure induced bronchoconstriction [ Time Frame: Day 1 to Day 7 ]
  3. Safety markers [ Time Frame: From screening to last follow-up visit which will take place between day 35 and day 42 ]
    between others: physical examination, vital signs, 12-lead ECG, clinical laboratory (hematology and serum chemistry), urine analysis, serology, adverse events

  4. Pharmacokinetic parameters: plasma concentrations of ALX-0171 [ Time Frame: Day 1 to Day 8 ]
  5. Immunogenicity: presence of anti-drug antibodies (ADA) in serum, presence of ADA in sputum [ Time Frame: From screening to last follow-up visit which will take place between day 35 and day 42 ]

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Adult male and female subjects aged 18-60 years (both included).
  2. Subjects must demonstrate a PC20 (concentration of the agonist in the inhaled substance leading to a fall in FEV1 of ≥20.0% of personal best at same visit) response to methacholine (MCh) concentrations of > 1 mg/mL and ≤ 8 mg/mL at screening.
  3. Subjects not on concomitant treatments except for

    1. medication that has no effect on hyperresponsiveness, bronchoconstriction or on lung function parameters
    2. respiratory medication for which subjects are able to discontinue their current treatment during the study period taking into account the respective wash-out periods as listed in the protocol.
    3. short-acting bronchodilators under certain conditions as specified in the protocol.
  4. Screening forced expiratory volume (FEV1) value of > 60.0% of the predicted normal value after a wash-out of respiratory medication as listed in the protocol.
  5. Subject has been informed both verbally and in writing about the objectives of the clinical trial, the methods, the anticipated benefits and potential risks and the discomfort to which he may be exposed, and has given written consent to participation in the trial prior to trial start and any trial-related procedure.
  6. Body weight according to a Body Mass Index ≥ 18.5 and ≤ 29.0 kg/m².
  7. Non-smokers or ex-smokers who have stopped smoking for at least 1 year prior to start of the clinical study. No history of smoking more than 10 pack years.
  8. Ability to inhale in an appropriate manner.
  9. Female subjects of childbearing potential and male subjects must agree to use appropriate methods of contraception as specified in the protocol.

Exclusion Criteria:

  1. Subjects with a pre-dose baseline FEV1 measurement on the first day (i.e. prior to the first inhalation of ALX-0171 placebo) which is below or equal to 60.0% of the predicted FEV1 value.
  2. Presence of clinically significant diseases other than asthma, hyperresponsive airways or atopic diseases (cardiovascular, renal, hepatic, gastrointestinal, haematological, neurological, genitourinary, autoimmune, endocrine, metabolic, etc.), which, in the opinion of the investigator, may either put the subject at risk because of participation in the trial, or diseases which may influence the results of the study or the subject's ability to take part in it.
  3. Presence of relevant pulmonary diseases (except asthma) or history of thoracic surgery.
  4. History or current evidence of clinically relevant allergies to drugs.
  5. Any absolute or relative contraindications for methacholine challenge: e.g., severe or moderate airflow limitation (FEV1 ≤ 60.0% predicted or < 1.5 L), heart attack or stroke in the last 3 months, uncontrolled hypertension, known aortic aneurysm, current use of cholinesterase inhibitor medication.
  6. Hospitalisation or emergency room treatment for acute asthma in the 3 months prior to screening, between screening and the start of the treatment period.
  7. Hospitalisation for longer than 24 hours for the management of an asthma exacerbation within the preceding 3 months of the screening visit or intubation (ever) for that named cause.
  8. History of allergic reactions to any active or inactive ingredients of the nebuliser solution.
  9. ECG abnormalities of clinical relevance.
  10. Clinically relevant abnormal heart rate and/or blood pressure as judged by the investigator.
  11. Proneness to orthostatic dysregulation, fainting, or blackouts.
  12. History (within the last 5 years) or presence of any malignancy except for basalioma.
  13. Clinically relevant abnormalities in clinical chemical, haematological or in any other laboratory variables.
  14. Chronic or clinically relevant acute infections.
  15. Clinically relevant positive results in any of the following virology tests: Hepatitis B surface antigen, Hepatitis C antibodies, human immunodeficiency virus (HIV)-1, and HIV -2 antibodies.
  16. Positive drug screen.
  17. History of previous administration of ALX-0171 or any other medication targeting the F-protein (e.g. palivizumab) or any other inhaled biologic. In any other case of use of biologics: 6 months, or the time of duration of the pharmacodynamic effect, or 10 times the half-life of the respective drug, whatever is longer, before first trial medication administration.
  18. History or presence of alcohol or drug abuse.
  19. Planned donation of germ cells, blood, organs, bone marrow during the course of the trial or within 6 months thereafter.
  20. Participation in another clinical trial with an investigational drug within the last month (defined as 1 month between last visit previous trial and Informed Consent Form (ICF)signature of the current trial).
  21. Blood donation within the last 30 days before screening.
  22. Lack of ability or willingness to give informed consent.
  23. Anticipated non-availability for trial visits/procedures.
  24. Anticipated lack of willingness or inability to cooperate adequately.
  25. Vulnerable subjects (e.g., persons kept in detention).
  26. Consumption of any xanthine derivates (such as -but not limited to-, caffeine, theophylline, chocolate) 6 hours before first procedure at each study visit.
  27. Pregnant or lactating women.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01909843

Gauting, Germany, 82131
Sponsors and Collaborators
Study Director: Steven De Bruyn, MD Ablynx NV

Responsible Party: Ablynx Identifier: NCT01909843     History of Changes
Other Study ID Numbers: ALX-0171-1.2/13
2012-005811-14 ( EudraCT Number )
First Posted: July 29, 2013    Key Record Dates
Last Update Posted: January 3, 2014
Last Verified: January 2014

Additional relevant MeSH terms:
Virus Diseases
Respiratory Syncytial Virus Infections
Pneumovirus Infections
Paramyxoviridae Infections
Mononegavirales Infections
RNA Virus Infections