AsthmaPhase 1NCT01470911
Safety, Tolerability, and Pharmacokinetics of Orally Inhaled DNAzyme Solution for Nebulisation in Healthy Male Subjects
A Phase 1 study testing SB010 in people with Asthma, run by Sterna Biologicals GmbH & Co. KG at 1 site in Germany.
Trial summary
Asthma is a chronic inflammatory bronchial disorder with three distinct components: airway hyper-responsiveness (respiratory hypersensitivity), airway inflammation, and intermittent airway obstruction. Read more about this study
- Who is it for?
- Ages 18 to 45 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Asthma
- What is being tested?
- SB010
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 46 participants
- Where
- 1 siteGermany
- Study dates
- Nov 2011to Dec 2011
- Phase
- Phase 1
- 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 18 to 45 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Written consent to participation in the trial prior to trial start and any trial-related procedure.
- Healthy male Caucasian subject - healthy based on a screening examination including medical history, without clinically relevant pathologies, physical examination, vital signs, ECG assessment, pulmonary function testing, and clinical laboratory results.
- Body weight according to a body mass index (BMI) between 18 and 29 kg/m2 (inclusive); body weight between 60 and 90 kg.
- Non-smokers or ex-smokers (stopped smoking for at least 5 years prior to start of the clinical study).
- Ability to inhale in an appropriate manner.
Who cannot join
- History or current evidence of clinically relevant allergies or idiosyncrasy to any drug or food.
- History of allergic reactions to any active or inactive component of the study medication.
- History or current evidence of any clinically relevant pulmonary, cardiovascular, hepatic, renal, gastrointestinal, haematological, endocrinological, metabolic, neurological, or psychiatric disease within the last 2 years.
- ECG abnormalities of clinical relevance (e.g., QTc according to Bazett's ³440 ms, PR ³210 ms; or QRS ³120 ms).
- Subjects with a resting heart rate <50 bpm, systolic blood pressure <100 mmHg, diastolic blood pressure <60 mmHg.
- Proneness to orthostatic dysregulation, fainting, or blackouts.
Show all 27Show fewer
- History or presence of any malignancy except for basalioma.
- Abnormalities in clinical chemical or haematologic variables considered medically relevant by the investigator.
- Chronic or acute infections.
- Positive results in any of the following virology tests: human immunodeficiency virus (HIV) antibodies and antigen, Anti-hepatitis B-core antibody, hepatitis B surface antigen (HBsAg) and anti-hepatitis C virus antibody.
- Positive drug screen.
- History of previous administration of any registered or investigational oligonucleotide-based drug.
- History or presence of alcohol or drug abuse.
- Treatment with any known enzyme inducing or inhibiting agents (e.g., St. John's Wort (Johanniskraut), barbiturates, phenothiazines, cimetidine, ketoconazole, etc.) within 30 days before administration of IMP or during the trial.
- Use of any medication (including over-the-counter medication, herbal products) except allowed concomitant medication within 2 weeks (for biologics: 6 months) before administration of IMP or within <10 times the elimination half-life of the respective drug, or the duration of the pharmacodynamic effect, whatever is longer.
- Consumption of any enzyme inducing or inhibiting aliments and beverages (e.g., broccoli, Brussels sprout, grapefruit, grapefruit juice, star fruit etc.) within 14 days prior to the IMP administration or during the trial.
- Consumption of any caffeine- or theophylline-containing product 48 h before administration of IMP.
- Consumption of alcohol within 48 h before administration of IMP.
- Vegetarian diet or other dietary habits, which would preclude the subject's acceptance of standardised meals.
- Surgery of the gastrointestinal tract except for appendectomy or herniotomy.
- Planned donation of germ cells, blood, organs, bone marrow during the course of the trial or within 6 months thereafter.
- Participation in another clinical trial with an investigational drug or device within the last 3 months. For biologics, the minimum exclusion period is at least 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 inclusion in this trial.
- Blood donation within the last 30 days before screening.
- Lack of ability or willingness to give informed consent.
- Anticipated non-availability for trial visits/procedures.
- Anticipated lack of willingness or inability to cooperate adequately.
- Vulnerable subjects (e.g., persons kept in detention).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase-I Study in Healthy Male Subjects to Investigate Safety, Tolerability and Pharmacokinetics of Orally Inhaled Single Doses of SB010, a Human GATA-3-specific DNAzyme Solution for Nebulisation.
Asthma is a chronic inflammatory bronchial disorder with three distinct components: airway hyper-responsiveness (respiratory hypersensitivity), airway inflammation, and intermittent airway obstruction. One of the characteristics of the disease is an inflammatory reaction of the immune system caused by cytokine production. A substantial number of asthma patients do not satisfactorily respond to steroid therapy and consequently have an unmet medical need for novel targeted therapies with improved specificity, tolerability, and compliance.
Novel therapeutic strategies for the treatment of chronic inflammatory diseases by targeting early disease-causing mechanisms are a promising approach for the treatment of asthma. The transcription factor GATA-3 plays a key role in mediating the asthmatic immune response and has been shown to be necessary and sufficient for the production of cytokines interleukin (IL)-4, IL-5, and IL-13. The active principle hgd40 of the investigational medicinal product SB010 belongs to a new class of antisense oligonucleotide therapeutics, the 10-23 DNA (deoxyribonucleic acid) zymes (antisense oligonucleotide). DNAzymes are catalytically active nucleic acids that cleave complementary RNA (ribonucleic acid) molecules. By cleaving GATA-3 mRNA hgd40 reduces specific cytokine production and thereby reduces key features of allergic airway inflammation.
Read more
DNAzymes are completely generated by chemical synthesis and can be produced under Good Manufacturing Practice (GMP) controlled conditions. The DNAzymes are not biological drugs, i.e. they are not generated by use of any living organism including cell culture or bacteria. The molecules are highly water-soluble and will be applied as solution directly in their synthesized form.
The current study will evaluate the safety and tolerability of increasing single doses of inhaled SB010 in healthy male subjects.
- Conditions
- Asthma
- Being tested
- SB010, Placebo
- Keywords
- Antisense oligonucleotide, Asthma, Healthy subjects, Phase 1, Transcription factor GATA-3, Oral inhalation
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SB010Drug
Six ascending dose groups (DG) are planned, with a total of 48 subjects. DG 1 and 2 will consist of n=6 subjects (n=3 receiving SB010, n=3 placebo). The following DG will consist of n=9 subjects (n=6 receiving SB010, n=3 placebo). The number of subjects to be exposed to active compound will be limited on a particular study day. Subjects of a particular DG will be divided into subgroups and exposed to the drug on different days. In DG 1 and 2, the time interval between the two administrations of the first subgroup will be at least 2 hours. In DG 3-6, the time interval between two subsequent administrations will be at least 1 hour.
Dose level (DL) 1: 0.4 mg hgd40/2 mL; DL 2: 2 mg hgd40/2 mL; DL 3: 5 mg hgd40/2 mL; DL 4: 10 mg hgd40/2 mL; DL 5: 20 mg hgd40/2 mL; DL 6: 40 mg hgd40/2 mL.
PlaceboDrug
Six ascending dose groups (DG) are planned, with a total of 48 subjects. DG 1 and 2 will consist of n=6 subjects (n=3 receiving SB010, n=3 placebo). The following DG will consist of n=9 subjects (n=6 receiving SB010, n=3 placebo). The number of subjects to be exposed to active compound will be limited on a particular study day. Subjects of a particular DG will be divided into subgroups and exposed to the drug on different days. In DG 1 and 2, the time interval between the two administrations of the first subgroup will be at least 2 hours. In DG 3-6, the time interval between two subsequent administrations will be at least 1 hour.
| Study group | Role | What they receive |
|---|---|---|
| SB010 | Experimental | The drug SB010 is administered in phosphate-buffered saline solution, inhaled via a controlled breathing system over a 5 to 10 min. Receives: Drug: SB010 |
| Placebo | Placebo comparator | The placebo (phosphate-buffered saline) is administered as a solution inhaled via a controlled breathing system over a 5 to 10 min. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Limiting dose of inhaled ascending single dose of SB010.
Safety will be monitored as adverse events, vital signs, clinical chemistry, haematology, urinalysis, electrocardiogram, pulmonary function testing, body temperature, overall tolerability.
Measured: Study period 4 days, follow up visit 12±2 days, end of study day 60±4 days; maximum of 78 days for a particular subject.
Secondary outcomes (4)
Number of participants with any dose-limiting adverse effects.
Safety will be monitored as adverse events, vital signs, clinical chemistry, haematology, urinalysis, electrocardiogram, pulmonary function testing, body temperature, overall tolerability.
Measured: Study period 4 days, follow up visit 12±2 days, end of study day 60±4 days; maximum of 78 days for a particular subject.
Maximum tolerated dose.
Safety will be monitored as adverse events, vital signs, clinical chemistry, haematology, urinalysis, electrocardiogram, pulmonary function testing, body temperature, overall tolerability.
Measured: Study period 4 days, follow up visit 12±2 days, end of study day 60±4 days; maximum of 78 days for a particular subject.
Single-dose plasma concentration of hgd40 over time after inhalation of SB010.
The following pharmacokinetic parameters will be determined in plasma samples over 4 days: Area under the plasma concentration-time curve; Concentration maximum; Time of maximum concentration; Apparent terminal elimination half-life; Area under the concentration-time curve until the last sampling time;
Measured: Day 1 to 4 of the study.
Feasibility of the inhalative technique.
Study participants will be instructed on the correct inhalation technique. Ability to breath in through the mouth and exhale through the nose will be assessed during the inhalation procedure. Forced Expiratory Volume in 1 second(FEV1*) will be monitored at screening and throughout the study after the single dose of the study drug: Days 1, 2, 3, 4, 12±2, and 60±4
*FEV1 = the maximal amount of air forcefully exhaled in one second
Measured: Day 1.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2011 (estimated)
- Study startNov 2011
- Primary completionDec 2011
- Study completionDec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AsthmaStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sterna Biologicals GmbH & Co. KG
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Wolfgang Timmer, MD, Principal investigator, CRS-Mannheim GmbH, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01470911
- Sponsor's protocol ID
- SB010/01/2011
- Other IDs
- 2011-002916-10
- Status last verified
- Nov 2012
- First submitted
- 31 Oct 2011
- Last updated
- 22 Nov 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase-I Study in Healthy Male Subjects to Investigate Safety, Tolerability and Pharmacokinetics of Orally Inhaled Single Doses of SB010, a Human GATA-3-specific DNAzyme Solution for Nebulisation.
- ClinicalTrials.gov ID
- NCT01470911
- Acronym / sponsor ID
- SB010/01/2011
- Conditions
- Asthma
- Keywords
- Antisense oligonucleotide, Asthma, Healthy subjects, Phase 1, Transcription factor GATA-3, Oral inhalation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- Sterna Biologicals GmbH & Co. KGIndustry (pharma, biotech, devices)
- Study start
- Nov 2011
- Primary completion
- Dec 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 11 Nov 2011 (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.
Asthma is a chronic inflammatory bronchial disorder with three distinct components: airway hyper-responsiveness (respiratory hypersensitivity), airway inflammation, and intermittent airway obstruction. One of the characteristics of the disease is an inflammatory reaction of the immune system caused by cytokine production. A substantial number of asthma patients do not satisfactorily respond to steroid therapy and consequently have an unmet medical need for novel targeted therapies with improved specificity, tolerability, and compliance.
Novel therapeutic strategies for the treatment of chronic inflammatory diseases by targeting early disease-causing mechanisms are a promising approach for the treatment of asthma. The transcription factor GATA-3 plays a key role in mediating the asthmatic immune response and has been shown to be necessary and sufficient for the production of cytokines interleukin (IL)-4, IL-5, and IL-13. The active principle hgd40 of the investigational medicinal product SB010 belongs to a new class of antisense oligonucleotide therapeutics, the 10-23 DNA (deoxyribonucleic acid) zymes (antisense oligonucleotide). DNAzymes are catalytically active nucleic acids that cleave complementary RNA (ribonucleic acid) molecules. By cleaving GATA-3 mRNA hgd40 reduces specific cytokine production and thereby reduces key features of allergic airway inflammation.
DNAzymes are completely generated by chemical synthesis and can be produced under Good Manufacturing Practice (GMP) controlled conditions. The DNAzymes are not biological drugs, i.e. they are not generated by use of any living organism including cell culture or bacteria. The molecules are highly water-soluble and will be applied as solution directly in their synthesized form.
The current study will evaluate the safety and tolerability of increasing single doses of inhaled SB010 in healthy male subjects.
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 |
|---|---|---|
| SB010 | Experimental | Drug: SB010The drug SB010 is administered in phosphate-buffered saline solution, inhaled via a controlled breathing system over a 5 to 10 min. |
| Placebo | Placebo comparator | Drug: PlaceboThe placebo (phosphate-buffered saline) is administered as a solution inhaled via a controlled breathing system over a 5 to 10 min. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Written consent to participation in the trial prior to trial start and any trial-related procedure.
- Healthy male Caucasian subject - healthy based on a screening examination including medical history, without clinically relevant pathologies, physical examination, vital signs, ECG assessment, pulmonary function testing, and clinical laboratory results.
- Body weight according to a body mass index (BMI) between 18 and 29 kg/m2 (inclusive); body weight between 60 and 90 kg.
- Non-smokers or ex-smokers (stopped smoking for at least 5 years prior to start of the clinical study).
- Ability to inhale in an appropriate manner.
Key exclusion criteria (27 listed)
- History or current evidence of clinically relevant allergies or idiosyncrasy to any drug or food.
- History of allergic reactions to any active or inactive component of the study medication.
- History or current evidence of any clinically relevant pulmonary, cardiovascular, hepatic, renal, gastrointestinal, haematological, endocrinological, metabolic, neurological, or psychiatric disease within the last 2 years.
- ECG abnormalities of clinical relevance (e.g., QTc according to Bazett's ³440 ms, PR ³210 ms; or QRS ³120 ms).
- Subjects with a resting heart rate <50 bpm, systolic blood pressure <100 mmHg, diastolic blood pressure <60 mmHg.
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 |
|---|---|---|
| SB010Six ascending dose groups (DG) are planned, with a total of 48 subjects. DG 1 and 2 will consist of n=6 subjects (n=3 receiving SB010, n=3 placebo). The following DG will consist of n=9 subjects (n=6 receiving SB010, n=3 placebo). The number of subjects to be exposed to active compound will be limited on a particular study day. Subjects of a particular DG will be divided into subgroups and exposed to the drug on different days. In DG 1 and 2, the time interval between the two administrations of the first subgroup will be at least 2 hours. In DG 3-6, the time interval between two subsequent administrations will be at least 1 hour. Dose level (DL) 1: 0.4 mg hgd40/2 mL; DL 2: 2 mg hgd40/2 mL; DL 3: 5 mg hgd40/2 mL; DL 4: 10 mg hgd40/2 mL; DL 5: 20 mg hgd40/2 mL; DL 6: 40 mg hgd40/2 mL. | Drug | SB010 |
| PlaceboSix ascending dose groups (DG) are planned, with a total of 48 subjects. DG 1 and 2 will consist of n=6 subjects (n=3 receiving SB010, n=3 placebo). The following DG will consist of n=9 subjects (n=6 receiving SB010, n=3 placebo). The number of subjects to be exposed to active compound will be limited on a particular study day. Subjects of a particular DG will be divided into subgroups and exposed to the drug on different days. In DG 1 and 2, the time interval between the two administrations of the first subgroup will be at least 2 hours. In DG 3-6, the time interval between two subsequent administrations will be at least 1 hour. | Drug | Placebo |
Primary outcome
Limiting dose of inhaled ascending single dose of SB010.
Time frame: Study period 4 days, follow up visit 12±2 days, end of study day 60±4 days; maximum of 78 days for a particular subject.
Safety will be monitored as adverse events, vital signs, clinical chemistry, haematology, urinalysis, electrocardiogram, pulmonary function testing, body temperature, overall tolerability.
4 secondary outcomes
Number of participants with any dose-limiting adverse effects.
Time frame: Study period 4 days, follow up visit 12±2 days, end of study day 60±4 days; maximum of 78 days for a particular subject.
Maximum tolerated dose.
Time frame: Study period 4 days, follow up visit 12±2 days, end of study day 60±4 days; maximum of 78 days for a particular subject.
Single-dose plasma concentration of hgd40 over time after inhalation of SB010.
Time frame: Day 1 to 4 of the study.
Feasibility of the inhalative technique.
Time frame: Day 1.
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 22 Nov 2012.
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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.
Wolfgang Timmer, MD principal investigator
CRS-Mannheim GmbH, Germany
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing SB010 in people with Asthma, run by Sterna Biologicals GmbH & Co. KG at 1 site in Germany.
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 5 inclusion and 27 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 22 Nov 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Limiting dose of inhaled ascending single dose of SB010. (time frame: Study period 4 days, follow up visit 12±2 days, end of study day 60±4 days; maximum of 78 days for a particular subject.). 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 22 Nov 2012.