AsthmaPhase 1NCT01554319
Safety, Tolerability, and Pharmacokinetics After Multiple Doses 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
- 36 participants
- Where
- 1 siteGermany
- Study dates
- Apr 2012to Aug 2012
- 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
- 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.
- Healthy male Caucasian subject, aged between 18 and 45 years (inclusive), assessed as 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 ≥18.0 and ≤29.0 kg/m2, and a body weight ≥60 and ≤90 kg.
- Non-smokers or ex-smokers who had stopped smoking for at least 5 years prior to start of the clinical study.
- Ability to inhale in an appropriate manner (Subjects will be trained to inhale using the AKITA2 APIXNEB® device with a placebo medication at the screening visit).
- The subject must agree:
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- to use two methods of contraception in combination with his female partner, if she is of childbearing potential; this combination of contraceptive methods must be used from screening until at least 6 months after the last dose of IMP. At least one of the contraception methods must be a barrier contraception method. Contraceptive methods allowed include the following: condoms, diaphragm in combination with a spermicide, intrauterine device as well as for female partners oral contraception, contraception implants, OR
- not to be sexually active at screening and accept using double-barrier contraception should he become sexually active during or within 6 months after the last dose of IMP, OR
- to have been surgically sterilised prior to screening and accept to use a barrier method of contraception as well, OR
- to have a partner who is post-menopausal and has had her last natural menstruation at least 24 months prior to screening, OR
- to have a partner who has had a hysterectomy prior to screening, OR
- to have a partner who has been surgically sterilised prior to screening
- All assessments will be performed within 2 to 14 days prior to first dose with the active compound or placebo.
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.
- Any history of allergic rhinitis or atopic disease. Subjects with total immunoglobulin E levels >150 kU/L will be excluded.
- 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 ≥440 ms, PR ≥210 ms; or QRS ≥120 ms).
- Subjects with a resting heart rate between 50 bpm and 90 bpm (inclusive), systolic blood pressure between 100 mmHg and 140 mmHg (inclusive), diastolic blood pressure between 60 mmHg and 90 mmHg (inclusive).
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- Proneness to orthostatic dysregulation, fainting, or blackouts.
- History or presence of any malignancy except for basalioma.
- Abnormalities in clinical chemical or haematological variables considered medically relevant by the investigator. Values for total leukocytes and neutrophils, gamma-glutamyltranspeptidase, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, bilirubin, and serum creatinine should be within normal ranges.
- Chronic or acute infections.
- Positive results in any of the following virology tests: human immunodeficiency virus antibodies and antigen, Anti-hepatitis B-core antibody, hepatitis B surface antigen and anti-hepatitis C virus antibody.
- Positive drug screen.
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 Multiple 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 generated completely 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 multiple doses of inhaled SB010 in healthy male subjects.
- Conditions
- Asthma
- Being tested
- SB010, Placebo (phosphate-buffered saline)
- 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
Three ascending dose groups are planned (Groups A, B, C), each consisting of 12 male subjects. Each of the 3 dose groups will be divided into 2 subgroups. First subgroup: 4 subjects (n=3 active compound, n=1 placebo); second subgroup: 8 subjects (n=6 active compound, n=2 placebo).
Each dose group will be investigated with a new group of 12 subjects (n=9 active compound, n=3 placebo). Dose escalation to next dose level will occur after satisfactory review of safety and tolerability and after review of the pharmacokinetic data (exposure control) of the preceding dose cohorts by the Safety Board.
Dose group A : 5 mg hgd40/2 mL; Dose group B: 10 mg hgd40/2 mL; Dose group C: 20 mg hgd40/2 mL.
Placebo (phosphate-buffered saline)Drug
Three ascending dose groups are planned (Groups A, B, C), each consisting of 12 male subjects. Each of the 3 dose groups will be divided into 2 subgroups. First subgroup: 4 subjects (n=3 active compound, n=1 placebo); second subgroup: 8 subjects (n=6 active compound, n=2 placebo).
Each dose group will be investigated with a new group of 12 subjects (n=9 active compound, n=3 placebo). Dose escalation to next dose level will occur after satisfactory review of safety and tolerability and after review of the pharmacokinetic data (exposure control) of the preceding dose cohorts by the Safety Board.
| Study group | Role | What they receive |
|---|---|---|
| SB010 | Experimental | The drug will be administered in phosphate-buffered saline solution, inhaled over 5 - 10 min, using a hand-held inhalation device.
Initial single dose on Day 1 (single-dose PK profile); after 48 h washout, twice-daily with a dosing interval of 12 h for 9 consecutive days (Days 3 to 11); last inhalation on Day 12. Receives: Drug: SB010 |
| Placebo | Placebo comparator | The placebo (phosphate-buffered saline) is administered as a solution, inhaled over 5 - 10 min, using a hand-held inhalation device.
Initial single dose on Day 1 (single-dose PK profile); after 48 h washout, twice-daily with a dosing interval of 12 h for 9 consecutive days (Days 3 to 11); last inhalation on Day 12. Receives: Drug: Placebo (phosphate-buffered saline) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Limiting dose of inhaled ascending multiple doses of SB010.
Safety will be monitored as adverse events, vital signs, clinical chemistry, haematology, coagulation, urinalysis, electrocardiogram, pulmonary function testing, body temperature, overall tolerability.
Measured: Up to Day 71±4 (maximum 89 days for a particular patient)
Secondary outcomes (3)
Number of participants with any dose-limiting adverse effects, after multiple doses of inhaled SB010.
Safety will be monitored as adverse events, vital signs, clinical chemistry, haematology, coagulation, urinalysis, electrocardiogram, pulmonary function testing, body temperature, overall tolerability.
Measured: Screening examination (Day 14 to 2 before first drug administration); Study period (Day 1 to 15); Follow-up visit (Days 23±2); Follow-up phone call (Day 41±3); End-of-study visit (Day 71±4). Maximum of 89 days for a particular subject.
Plasma concentration of hgd40 over time after multiple inhaled doses of SB010.
The following pharmacokinetic parameters will be determined over 15 days using plasma samples, after a single dose on Day 1 and after repeated dosing at steady state on Day 12:
Area under the plasma concentration-time curve: from 0 to 12h, over 12h (dosing interval) after the last administration in steady state, and extrapolated to infinity.
Concentration maximum.
Time of maximum concentration.
Terminal disposition rate constant and the respective half-life.
Accumulation index.
Measured: Study period (Day 1 to 15).
Plasma concentration of hgd40 over time after multiple inhaled doses of SB010 (Dose proportionality over time).
Dose proportionality# after a single dose on Day 1 and after repeated dosing at steady state on Day 12 will be assessed across doses using the power model.
#Dose proportionality implies linear pharmacokinetics. The rates of absorption, distribution, metabolism, and elimination remain constant over the dose range. Thus, plasma concentration, area under the plasma concentration-time curve, maximum plasma concentration, and urinary recovery should increase in direct proportion to the dose.
Measured: Study period (Day 1 to 15).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2012 (estimated)
- Study startApr 2012
- Primary completionAug 2012
- Study completionAug 2012
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
- 36 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
- NCT01554319
- Sponsor's protocol ID
- SB010/02/2011
- Other IDs
- 2011-005782-20
- Status last verified
- Nov 2012
- First submitted
- 8 Mar 2012
- Last updated
- 27 Nov 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 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 Multiple Doses of SB010, a Human GATA-3-specific DNAzyme Solution for Nebulisation
- ClinicalTrials.gov ID
- NCT01554319
- Acronym / sponsor ID
- SB010/02/2011
- 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
- 36 participants (actual)
- Lead sponsor
- Sterna Biologicals GmbH & Co. KGIndustry (pharma, biotech, devices)
- Study start
- Apr 2012
- Primary completion
- Aug 2012 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 14 Mar 2012 (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 generated completely 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 multiple 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 will be administered in phosphate-buffered saline solution, inhaled over 5 - 10 min, using a hand-held inhalation device. Initial single dose on Day 1 (single-dose PK profile); after 48 h washout, twice-daily with a dosing interval of 12 h for 9 consecutive days (Days 3 to 11); last inhalation on Day 12. |
| Placebo | Placebo comparator | Drug: Placebo (phosphate-buffered saline)The placebo (phosphate-buffered saline) is administered as a solution, inhaled over 5 - 10 min, using a hand-held inhalation device. Initial single dose on Day 1 (single-dose PK profile); after 48 h washout, twice-daily with a dosing interval of 12 h for 9 consecutive days (Days 3 to 11); last inhalation on Day 12. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- 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.
- Healthy male Caucasian subject, aged between 18 and 45 years (inclusive), assessed as 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 ≥18.0 and ≤29.0 kg/m2, and a body weight ≥60 and ≤90 kg.
- Non-smokers or ex-smokers who had stopped smoking for at least 5 years prior to start of the clinical study.
- Ability to inhale in an appropriate manner (Subjects will be trained to inhale using the AKITA2 APIXNEB® device with a placebo medication at the screening visit).
Key exclusion criteria (12 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.
- Any history of allergic rhinitis or atopic disease. Subjects with total immunoglobulin E levels >150 kU/L will be excluded.
- 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 ≥440 ms, PR ≥210 ms; or QRS ≥120 ms).
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 |
|---|---|---|
| SB010Three ascending dose groups are planned (Groups A, B, C), each consisting of 12 male subjects. Each of the 3 dose groups will be divided into 2 subgroups. First subgroup: 4 subjects (n=3 active compound, n=1 placebo); second subgroup: 8 subjects (n=6 active compound, n=2 placebo). Each dose group will be investigated with a new group of 12 subjects (n=9 active compound, n=3 placebo). Dose escalation to next dose level will occur after satisfactory review of safety and tolerability and after review of the pharmacokinetic data (exposure control) of the preceding dose cohorts by the Safety Board. Dose group A : 5 mg hgd40/2 mL; Dose group B: 10 mg hgd40/2 mL; Dose group C: 20 mg hgd40/2 mL. | Drug | SB010 |
| Placebo (phosphate-buffered saline)Three ascending dose groups are planned (Groups A, B, C), each consisting of 12 male subjects. Each of the 3 dose groups will be divided into 2 subgroups. First subgroup: 4 subjects (n=3 active compound, n=1 placebo); second subgroup: 8 subjects (n=6 active compound, n=2 placebo). Each dose group will be investigated with a new group of 12 subjects (n=9 active compound, n=3 placebo). Dose escalation to next dose level will occur after satisfactory review of safety and tolerability and after review of the pharmacokinetic data (exposure control) of the preceding dose cohorts by the Safety Board. | Drug | Placebo |
Primary outcome
Limiting dose of inhaled ascending multiple doses of SB010.
Time frame: Up to Day 71±4 (maximum 89 days for a particular patient)
Safety will be monitored as adverse events, vital signs, clinical chemistry, haematology, coagulation, urinalysis, electrocardiogram, pulmonary function testing, body temperature, overall tolerability.
3 secondary outcomes
Number of participants with any dose-limiting adverse effects, after multiple doses of inhaled SB010.
Time frame: Screening examination (Day 14 to 2 before first drug administration); Study period (Day 1 to 15); Follow-up visit (Days 23±2); Follow-up phone call (Day 41±3); End-of-study visit (Day 71±4). Maximum of 89 days for a particular subject.
Plasma concentration of hgd40 over time after multiple inhaled doses of SB010.
Time frame: Study period (Day 1 to 15).
Plasma concentration of hgd40 over time after multiple inhaled doses of SB010 (Dose proportionality over time).
Time frame: Study period (Day 1 to 15).
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 27 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 13 inclusion and 12 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 27 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 multiple doses of SB010. (time frame: Up to Day 71±4 (maximum 89 days for a particular patient)). 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 27 Nov 2012.