Chronic Obstructive Pulmonary Disease (COPD)Phase 4AIACENCT02417649
Advanced Immunological Approach in COPD Exacerbation
A Phase 4 study testing Ismigen in people with Chronic Obstructive Pulmonary Disease (COPD), run by Lallemand Pharma AG at 13 sites in Italy.
Trial summary
Chronic obstructive pulmonary disease (COPD) are characterized by frequent relapses, often resulting from common bacterial infections. Enhancing the immune response in these patients may decrease the frequency of these relapses. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Chronic Obstructive Pulmonary Disease (COPD)
- What is being tested?
- Ismigen
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 288 participants
- Where
- 13 sitesItaly
- Study dates
- Sep 2009to Jul 2013
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with documented moderate, severe and very severe COPD
- Age greater than or equal to 40 years.
- Female patient must be non-lactating and of non-childbearing potential, surgically sterile, or using effective contraception.
- Patients must have WHO performance status of 0, 1 or 2.
- Patients must have adequate hematological, renal and liver function as defined by laboratory values below performed within 14 days, inclusive, prior to study randomization.
- Smokers, ex-smokers can be included but the smoking status is acquired and accurately recorded
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- Absolute neutrophil count (ANC) ≥ 2.0 x 109/l.
- Platelet count ≥ 100 x 109/l.
- Hemoglobin ≥ 10 g/dl (> 6.2 mmol/l).
- Urea and serum creatinine <1.5 times upper limit of laboratory normal (ULN).
- Total serum bilirubin <1.5 times ULN.
- ALAT or ASAT <5 times ULN.
- Alkaline phosphatase <5 times ULN.
- Gammaglutamyltransferase (GGT) <5 times ULN.
- LDH <5 times ULN.
- Before patient randomization, written informed consent must be given according to ICH/GCP, and national/local regulations.
Who cannot join
- Patients who had received any prior antineoplastic drug therapy or immunosuppressive drugs.
- Patients under continuous treatment with systemic steroids.
- Presence of severe cardiac disease including uncontrolled angina pectoris and myocardial infarction within 6 months, uncontrolled high blood pressure.
- Presence of severe respiratory disease as identified from spirometry and/or chest X ray.
- Presence of any other uncontrolled severe medical condition including active gastroduodenal ulcer, alcohol disorders ( hepatitis, Korsakoff syndrome..), diabetes, active or uncontrolled infection, evolutive intracranial hypertension"
- Patients pregnant or nursing at the beginning of the study.
- Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
Italy13 sites
Broncopneumology and Allergology Unit, Abbiategrasso hospital
Abbiategrasso
Specialistic Rehabilitation (Pneumolgi Unit),"Carlo Mira" hospital
Casorate Primo, PV
Respiratory Physiopatology Unit, Mellino Mellini hospital
Chiari
Pneumology Unit, Cremona hospital
Cremona
Allergy and Respiratory Diseases Clinic, San Martino hospital
Genova
Pneumology Department - San Paolo Hospital
Milan, Milan, 20142
Pneumology Unit, San Gerardo hospital
Monza
Complex structure of Pulmonary Allergy, Cardarelli hospital
Naples
Complex structure of Pulmonary Rehabilitation, Cardarelli hospital
Naples
Respiratory and Pulmonary desease Unit - IRCCS San Matteo
Pavia, Pavia, 27100
Rehabilitation Pneumology Unit, IRCCS San Raffaele Pisana
Rome, RM
Respiratory Clinical Pharmacology, Department of Internal Medicine, Tor Vergata Hospital
Rome, RM
Respiratory Physiopatology and Pneumology Unit, Di Circolo Predabissi-Melegnano hospital
Vizzolo Predabissi, MI
About this study
Official title: Sublingual Administration of a Polyvalent Mechanical Bacterial Lysate in Patients With Moderate, Severe or Very Severe COPD According to GOLD Classification: a Multicenter, Double Blind, Randomized, Controlled, Phase IV Study
Chronic obstructive pulmonary disease (COPD) are characterized by frequent relapses, often resulting from common bacterial infections. Enhancing the immune response in these patients may decrease the frequency of these relapses. The use of a mechanic Polyvalent Bacterial Lysate (PMBL, Ismigen, 13 bacterial strains)may enhance the immune response and therefore help significantly to the control of relapse in these patients.
In the current study the effect of the administration of the PBML to patients older than 40 years, with moderate, severe or very severe COPD, in good or discrete physical condition on the number of relapses in an observation period of 12 months. In addition, the effect of the PMBL on the duration of the interval between relapses, on relapse symptoms, on the use of other drugs, on the number of days of absence of work, on the number of hospitalizations and duration thereof and on potential toxicity of the treatment.
Read the detailed description
Ancillary Study at the center of Genoa:
To investigate in a subgroup of patient, taking part in the AIACE study, the ability of PMBL to induce an Ig response, to modify the NK blood pattern, and to modulate inflammatory parameters (e.g. CRP).
Material \& Methods:
30 patients who were enrolled at the Respiratory Department of Genoa University during the AIACE trial and double blind randomly treated with bacterial lysate or placebo, will participate in this ancillary study.
A further informed consent to participate in this laboratory trial will be requested to the patient besides the already ethical procedure approved for the AIACE study.
In order to assess the enhancement of the concentration of salivary antibodies, a sample of salivary fluid (SF) will be collected at day 0 using Salivette (Starsted, Germany, used according to the manufacture's instructions) and stored frozen until assayed. Then, treatment with PMBL will be carried out for ten days. After twenty-day rest (day 30), at the end of first treatment course (day 90) at the beginning and at the end of the second drug course (day 180, 210) and at the end of the study (day 360), a SF sample will be collected and stored frozen.
Besides the AIACE laboratory procedure already approved, a further blood sample (6 glass tubes) will be collected for peripheral NK blood phenotyping and CRP dosage.
Purified NK cells will obtained from peripheral blood sample at time 0, 90 and 360 by negative selection by using the NK cell isolation Kit (Miltenyi Biotech, Bergisch Gladbach - Germany) following the manufacturer instructions. The NK cell populations are assessed for purity and only those homogeneously displaying CD3-CD14-CD15-CD19- phenotype are selected.
Cells obtained as above described will be analyzed (time t0) by flow cytometry using the following mAbs: anti-CD3, anti-CD56, anti-NKp30, anti-NKp46, anti-NKp44, anti-NKG2D, anti-CD158B1/B2j, anti-KIR p70, anti-CD159A , anti-CD226 (Immunotech -Marseille, France).
In order to assess the efficacy of PMBL on systemic inflammation CRP will be evaluated at day 0 90 and 360. Finally, special T cell subpopulations, such as regulatory T cells, will be assayed on collected samples, together with the concentration of circulating chemokines, cytokines and inflammation-related molecules using a specific immunobeads and flow cytometry.
- Being tested
- Placebo, Ismigen
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboBiological
- The placebo will be administered for a period of three months. The first ten days of each month, one tablet per day will be given. The tablet will be melted under the tongue. After the ten day therapy, a twenty day of rest will be provided. Then the second and the third month the administration schedule will be identical.
- Three months of rest, according to the indications, will be allowed.
- A second cycle (the same as point 1.) will be performed
- A second three month rest (according to point 2.) will be provided.
IsmigenBiological
- The tablet will be administered for a period of three months. The first ten days of each month, one tablet per day will be given. The tablet will be melted under the tongue. After the ten day therapy, a twenty day of rest will be provided. Then the second and the third month the administration schedule will be identical.
- Three months of rest, according to the indications, will be allowed.
- A second cycle (the same as point 1.) will be performed
- A second three month rest (according to point 2.) will be provided.
| Study group | Role | What they receive |
|---|---|---|
| Ismigen | Experimental | Treatment over 3 successive months. One sublingual tablet every day on the first ten days of each month, followed by twenty days of rest. Receives: Biological: Ismigen |
| Placebo | Placebo comparator | Treatment over 3 successive months. One sublingual tablet every day on the first ten days of each month, followed by twenty days of rest. Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
To demonstrate the clinical efficacy of Ismigen in patients with moderate, severe and very severe COPD (M/S/VS-COPD) according to GOLD classification, in terms of reduction of the number of exacerbations in a 12 month observation period.
Measured: 1 year
Secondary outcomes (9)
Effect of Ismigen on the interval between each exacerbation.
Measured: 1 year
Effect of Ismigen on disease symptoms (fever, dyspnoea).
Measured: 1 year
Ability of Ismigen to reduce the use of other drugs (antibiotics, antinflammatory drugs, bronchodilators, mucolytics, etc.) in patients with documented M/S/VS-COPD.
Measured: 1 year
Ability of Ismigen to reduce the number of days of absence from work in patients with documented M/S/VS-COPD.
Measured: 1 year
Number of patients with adverse events as a measure of safety and tolerabiity.
Measured: 1 year
Impact on quality of life assessed with a generic health survey (SF-12) and a specific (CCIQ) instrument.
Measured: 1 year
Ability of Ismigen (PMBL) to induce immunological and inflammatory modulatory responses
Ancillary study in a subgroup of patient from the AIACE study, the measure the ability of PMBL to induce an Ig response, to modify the NK blood pattern, and to modulate inflammatory parameters (e.g. CRP).
30 patients who were enrolled at the Respiratory Department of Genoa University during the AIACE trial and double blind randomly treated with bacterial lysate or placebo, will participate in this ancillary study.
Measured: 1 year
Effect of Ismigen on the number of hospitalizations.
Measured: 1 year
Effect of Ismigen on the duration of hospitalizations.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2015 (estimated)
- Study startSep 2009
- Primary completionJul 2013
- Study completionJul 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Obstructive Pulmonary Disease (COPD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 288 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lallemand Pharma AG
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Sprim Advanced Life Sciences
- Responsible party
- Sponsor
- Investigators
- Giorgio Walter Canonica, Prof. MD, Principal investigator, University of Genova
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02417649
- Sponsor's protocol ID
- PIRRI/CT/001
- Acronym
- AIACE
- Status last verified
- Apr 2015
- First submitted
- 14 Oct 2013
- Last updated
- 15 Apr 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sublingual Administration of a Polyvalent Mechanical Bacterial Lysate in Patients With Moderate, Severe or Very Severe COPD According to GOLD Classification: a Multicenter, Double Blind, Randomized, Controlled, Phase IV Study
- ClinicalTrials.gov ID
- NCT02417649
- Acronym / sponsor ID
- AIACE / PIRRI/CT/001
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 288 participants (actual)
- Lead sponsor
- Lallemand Pharma AGIndustry (pharma, biotech, devices)
- Collaborators
- Sprim Advanced Life Sciences
- Study start
- Sep 2009
- Primary completion
- Jul 2013 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 15 Apr 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Chronic obstructive pulmonary disease (COPD) are characterized by frequent relapses, often resulting from common bacterial infections. Enhancing the immune response in these patients may decrease the frequency of these relapses. The use of a mechanic Polyvalent Bacterial Lysate (PMBL, Ismigen, 13 bacterial strains)may enhance the immune response and therefore help significantly to the control of relapse in these patients.
In the current study the effect of the administration of the PBML to patients older than 40 years, with moderate, severe or very severe COPD, in good or discrete physical condition on the number of relapses in an observation period of 12 months. In addition, the effect of the PMBL on the duration of the interval between relapses, on relapse symptoms, on the use of other drugs, on the number of days of absence of work, on the number of hospitalizations and duration thereof and on potential toxicity of the treatment.
Detailed description
Ancillary Study at the center of Genoa:
To investigate in a subgroup of patient, taking part in the AIACE study, the ability of PMBL to induce an Ig response, to modify the NK blood pattern, and to modulate inflammatory parameters (e.g. CRP).
Material \& Methods:
30 patients who were enrolled at the Respiratory Department of Genoa University during the AIACE trial and double blind randomly treated with bacterial lysate or placebo, will participate in this ancillary study.
A further informed consent to participate in this laboratory trial will be requested to the patient besides the already ethical procedure approved for the AIACE study.
In order to assess the enhancement of the concentration of salivary antibodies, a sample of salivary fluid (SF) will be collected at day 0 using Salivette (Starsted, Germany, used according to the manufacture's instructions) and stored frozen until assayed. Then, treatment with PMBL will be carried out for ten days. After twenty-day rest (day 30), at the end of first treatment course (day 90) at the beginning and at the end of the second drug course (day 180, 210) and at the end of the study (day 360), a SF sample will be collected and stored frozen.
Besides the AIACE laboratory procedure already approved, a further blood sample (6 glass tubes) will be collected for peripheral NK blood phenotyping and CRP dosage.
Purified NK cells will obtained from peripheral blood sample at time 0, 90 and 360 by negative selection by using the NK cell isolation Kit (Miltenyi Biotech, Bergisch Gladbach - Germany) following the manufacturer instructions. The NK cell populations are assessed for purity and only those homogeneously displaying CD3-CD14-CD15-CD19- phenotype are selected.
Cells obtained as above described will be analyzed (time t0) by flow cytometry using the following mAbs: anti-CD3, anti-CD56, anti-NKp30, anti-NKp46, anti-NKp44, anti-NKG2D, anti-CD158B1/B2j, anti-KIR p70, anti-CD159A , anti-CD226 (Immunotech -Marseille, France).
In order to assess the efficacy of PMBL on systemic inflammation CRP will be evaluated at day 0 90 and 360. Finally, special T cell subpopulations, such as regulatory T cells, will be assayed on collected samples, together with the concentration of circulating chemokines, cytokines and inflammation-related molecules using a specific immunobeads and flow cytometry.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ismigen | Experimental | Biological: IsmigenTreatment over 3 successive months. One sublingual tablet every day on the first ten days of each month, followed by twenty days of rest. |
| Placebo | Placebo comparator | Biological: PlaceboTreatment over 3 successive months. One sublingual tablet every day on the first ten days of each month, followed by twenty days of rest. |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Patients with documented moderate, severe and very severe COPD
- Age greater than or equal to 40 years.
- Female patient must be non-lactating and of non-childbearing potential, surgically sterile, or using effective contraception.
- Patients must have WHO performance status of 0, 1 or 2.
- Patients must have adequate hematological, renal and liver function as defined by laboratory values below performed within 14 days, inclusive, prior to study randomization.
Key exclusion criteria (7 listed)
- Patients who had received any prior antineoplastic drug therapy or immunosuppressive drugs.
- Patients under continuous treatment with systemic steroids.
- Presence of severe cardiac disease including uncontrolled angina pectoris and myocardial infarction within 6 months, uncontrolled high blood pressure.
- Presence of severe respiratory disease as identified from spirometry and/or chest X ray.
- Presence of any other uncontrolled severe medical condition including active gastroduodenal ulcer, alcohol disorders ( hepatitis, Korsakoff syndrome..), diabetes, active or uncontrolled infection, evolutive intracranial hypertension"
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Placebo1. The placebo will be administered for a period of three months. The first ten days of each month, one tablet per day will be given. The tablet will be melted under the tongue. After the ten day therapy, a twenty day of rest will be provided. Then the second and the third month the administration schedule will be identical. 2. Three months of rest, according to the indications, will be allowed. 3. A second cycle (the same as point 1.) will be performed 4. A second three month rest (according to point 2.) will be provided. | Biological | Placebo |
| Ismigen1. The tablet will be administered for a period of three months. The first ten days of each month, one tablet per day will be given. The tablet will be melted under the tongue. After the ten day therapy, a twenty day of rest will be provided. Then the second and the third month the administration schedule will be identical. 2. Three months of rest, according to the indications, will be allowed. 3. A second cycle (the same as point 1.) will be performed 4. A second three month rest (according to point 2.) will be provided. | Biological | Ismigen |
Primary outcome
To demonstrate the clinical efficacy of Ismigen in patients with moderate, severe and very severe COPD (M/S/VS-COPD) according to GOLD classification, in terms of reduction of the number of exacerbations in a 12 month observation period.
Time frame: 1 year
9 secondary outcomes
Effect of Ismigen on the interval between each exacerbation.
Time frame: 1 year
Effect of Ismigen on disease symptoms (fever, dyspnoea).
Time frame: 1 year
Ability of Ismigen to reduce the use of other drugs (antibiotics, antinflammatory drugs, bronchodilators, mucolytics, etc.) in patients with documented M/S/VS-COPD.
Time frame: 1 year
Ability of Ismigen to reduce the number of days of absence from work in patients with documented M/S/VS-COPD.
Time frame: 1 year
Number of patients with adverse events as a measure of safety and tolerabiity.
Time frame: 1 year
Impact on quality of life assessed with a generic health survey (SF-12) and a specific (CCIQ) instrument.
Time frame: 1 year
Ability of Ismigen (PMBL) to induce immunological and inflammatory modulatory responses
Time frame: 1 year
Effect of Ismigen on the number of hospitalizations.
Time frame: 1 year
Effect of Ismigen on the duration of hospitalizations.
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Apr 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Giorgio Walter Canonica, Prof. MD principal investigator
University of Genova
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ismigen in people with Chronic Obstructive Pulmonary Disease (COPD), run by Lallemand Pharma AG at 13 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To demonstrate the clinical efficacy of Ismigen in patients with moderate, severe and very severe COPD (M/S/VS-COPD) according to GOLD classification, in terms of reduction of the number of exacerbations in a 12 month observation period. (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Apr 2015.