Healthy VolunteersPhase 1NCT04105205
First-In-Human Study of Apramycin
A Phase 1 study testing Apramycin injection in people with Healthy Volunteers, run by Juvabis AG at 1 site in Germany.
Trial summary
This is a first-in-human study to assess the safety, tolerability and pharmacokinetics of escalating single doses of apramycin. This trial will be conducted as a single ascending dose trial in up to 5 sequential dose cohorts (group-comparison). Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- Apramycin injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteGermany
- Study dates
- 25 Sep 2019to 16 Oct 2020
- 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
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy male and female subjects of non-childbearing potential, 18-45 years of age (both inclusive), body mass index 18.0 - 29.9 kg/m2 (inclusive) and body weight from 50 to 100 kg (inclusive).
- Glomerular filtration rate (GFR) ≥ 90 mL/min /1.73 m2.
- Subjects with systemic hearing, with air conduction thresholds no worse than 20 decibels (dB) hearing loss for the frequencies 0.5-1-2-4-6-8 kilohertz (kHz) bilaterally and, no threshold asymmetry ≥ 20 dB at any frequency, normal (reproducibility 70% or better) transient evoked otoacoustic emissions (TEOAE).
- From the signing of the informed consent until the last follow-up visit, subjects must be willing to avoid exposure to loud noise and Subjects must be willing to avoid excessive physical exercise within 48 h prior to dosing.
- Normal blood pressure and pulse rate, ECG recording without clinically significant abnormalities.
- Thyroid-stimulating hormone, free triiodothyronine and free thyroxine within the reference ranges.
- Having had no febrile or infectious illness for at least 7 days prior to the first administration of the Investigational medicinal product (IMP) of the study.
- Normal microscopic findings in the ears, normal tympanic membrane mobility and stapedial reflex present.
Who cannot join
- Vegetarian or vegan.
- Demonstrating excess in xanthine consumption.
- More than low-risk alcohol consumption (men: ≥24 g of pure alcohol regularly per day; women: ≥12 g of pure alcohol regularly per day).
- Any history of alcohol or drug abuse or a positive urine drug screen test. Positive alcohol breath test.
- Consumption of xanthine-containing food or beverages within 48 h before dosing.
- Smokers smoking more than 10 cigarettes or equivalent per day.
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- Exposure to loud noise within 3 days prior to drug administration.
- Taking any medication on a regular basis, with the exception of solitary doses of up to 1000 mg paracetamol.
- Use of any investigational drug product within 30 days or 5 half-lives before screening.
- Use of aminoglycosides or other antibiotics within 3 months prior to screening.
- Use of neuromuscular blocking agents within 1 week or 5 half-lives prior to screening.
- Use of potentially nephrotoxic medication 2 weeks prior to the drug administration.
- Any history of drug hypersensitivity, asthma, urticaria or other severe allergic diathesis as well as hay fever with ongoing symptoms.
- Any history of hypersensitivity to aminoglycosides.
- Any history or signs of acute, chronic or recurrent metabolic, renal, hepatic, pulmonary, gastrointestinal, neurological, neuromuscular disorders, endocrinological, immunological, psychiatric or cardiovascular disease, myopathies, and bleeding tendency.
- Problems with hearing and/or balance.
- Previous injury or surgery to the middle or inner ears, family history of hearing loss before the age of 60.
- Genetic predisposition to aminoglycoside-driven ototoxicity.
- Laboratory values outside the reference range that are of clinical relevance.
- Positive test for HIV antibodies, hepatitis B-virus surface antigen, or anti-hepatitis C-virus antibodies.
- Blood or plasma donation of 500 mL within 3 months or more than 100 mL within 30 days before signing an informed consent to this trial.
- Judged by the investigator to have occupational noise exposure of high risk during the trial.
- Positive test for SARS-CoV-2.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of Apramycin Administered Intravenously in Healthy Adults.
This is a first-in-human study to assess the safety, tolerability and pharmacokinetics of escalating single doses of apramycin. This trial will be conducted as a single ascending dose trial in up to 5 sequential dose cohorts (group-comparison). Each cohort will consist of 8 healthy subjects, 6 will receive apramycin and 2 placebo.
- Conditions
- Healthy Volunteers
- Being tested
- Apramycin injection, Placebo injection
- Keywords
- Anti-Bacterial Agents
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Apramycin injectionDrug
30-min infusion
Placebo injectionDrug
30-min infusion
| Study group | Role | What they receive |
|---|---|---|
| Apramycin injection in escalating doses | Experimental | Apramycin, solution for infusion. Receives: Drug: Apramycin injection |
| Placebo | Placebo comparator | Physiological saline, solution for infusion. Receives: Drug: Placebo injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Type and incidence of treatment-emergent adverse events (TEAEs) until 2 weeks after dosing.
Measured: until 2 weeks after dosing
Type and incidence of TEAEs related to auditory and vestibular function tests.
Measured: until 3 months after dosing
Number of subjects with clinically significant vital sign measurement blood pressure.
Frequency is defined as number of subjects with clinically significant observations.
Measured: until 2 weeks after dosing
Number of subjects with clinically significant vital sign measurement pulse rate.
Frequency is defined as number of subjects with clinically significant observations.
Measured: until 2 weeks after dosing
Number of subjects with clinically significant observation in physical examination.
Frequency is defined as number of subjects with clinically significant observations.
Measured: until 2 weeks after dosing
Number of subjects with clinically significant changes in clinical laboratory parameters.
Frequency is defined as number of subjects with clinically significant observations.
Measured: until 2 weeks after dosing
Number of subjects with clinically significant changes in ECG parameters.
ECG parameters include heart rate and PQ, QT, RS. Frequency is defined as number of subjects with clinically significant observations.
Measured: until 2 weeks after dosing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2019
- Study start25 Sep 2019
- Primary completion16 Jul 2020
- Study completion16 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Healthy VolunteersStudies 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Juvabis AG
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Innovative Medicines Initiative
- Responsible party
- Sponsor
- Investigators
- Armin Schultz, Dr.med., Principal investigator, CRS Clinical Research Services Mannheim GmbH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04105205
- Sponsor's protocol ID
- JUV18-01
- Status last verified
- Nov 2020
- First submitted
- 12 Sep 2019
- Last updated
- 23 Feb 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Roch M, Sierra R, Sands K, Martins WMBS, Schrenzel J, Walsh TR, Gales AC, Andrey DO. Vertical and horizontal dissemination of an IncC plasmid harbouring rmtB 16S rRNA methylase gene, conferring resistance to plazomicin, among invasive ST258 and ST16 KPC-producing Klebsiella pneumoniae. J Glob Antimicrob Resist. 2021 Mar;24:183-189. doi: 10.1016/j.jgar.2020.12.006. Epub 2020 Dec 26.
PubMed 33373732
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of Apramycin Administered Intravenously in Healthy Adults.
- ClinicalTrials.gov ID
- NCT04105205
- Acronym / sponsor ID
- JUV18-01
- Conditions
- Healthy Volunteers
- Keywords
- Anti-Bacterial Agents
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Juvabis AGIndustry (pharma, biotech, devices)
- Collaborators
- Innovative Medicines Initiative
- Study start
- 25 Sep 2019 (actual)
- Primary completion
- 16 Jul 2020 (actual)
- Study completion
- 16 Oct 2020 (actual)
- First posted
- 26 Sep 2019 (actual)
- 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.
This is a first-in-human study to assess the safety, tolerability and pharmacokinetics of escalating single doses of apramycin. This trial will be conducted as a single ascending dose trial in up to 5 sequential dose cohorts (group-comparison). Each cohort will consist of 8 healthy subjects, 6 will receive apramycin and 2 placebo.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Apramycin injection in escalating doses | Experimental | Drug: Apramycin injectionApramycin, solution for infusion. |
| Placebo | Placebo comparator | Drug: Placebo injectionPhysiological saline, solution for infusion. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Healthy male and female subjects of non-childbearing potential, 18-45 years of age (both inclusive), body mass index 18.0 - 29.9 kg/m2 (inclusive) and body weight from 50 to 100 kg (inclusive).
- Glomerular filtration rate (GFR) ≥ 90 mL/min /1.73 m2.
- Subjects with systemic hearing, with air conduction thresholds no worse than 20 decibels (dB) hearing loss for the frequencies 0.5-1-2-4-6-8 kilohertz (kHz) bilaterally and, no threshold asymmetry ≥ 20 dB at any frequency, normal (reproducibility 70% or better) transient evoked otoacoustic emissions (TEOAE).
- From the signing of the informed consent until the last follow-up visit, subjects must be willing to avoid exposure to loud noise and Subjects must be willing to avoid excessive physical exercise within 48 h prior to dosing.
- Normal blood pressure and pulse rate, ECG recording without clinically significant abnormalities.
Key exclusion criteria (23 listed)
- Vegetarian or vegan.
- Demonstrating excess in xanthine consumption.
- More than low-risk alcohol consumption (men: ≥24 g of pure alcohol regularly per day; women: ≥12 g of pure alcohol regularly per day).
- Any history of alcohol or drug abuse or a positive urine drug screen test. Positive alcohol breath test.
- Consumption of xanthine-containing food or beverages within 48 h before dosing.
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 |
|---|---|---|
| Apramycin injection30-min infusion | Drug | Apramycin injection in escalating doses |
| Placebo injection30-min infusion | Drug | Placebo |
Primary outcome
Type and incidence of treatment-emergent adverse events (TEAEs) until 2 weeks after dosing.
Time frame: until 2 weeks after dosing
Type and incidence of TEAEs related to auditory and vestibular function tests.
Time frame: until 3 months after dosing
Number of subjects with clinically significant vital sign measurement blood pressure.
Time frame: until 2 weeks after dosing
Frequency is defined as number of subjects with clinically significant observations.
Number of subjects with clinically significant vital sign measurement pulse rate.
Time frame: until 2 weeks after dosing
Frequency is defined as number of subjects with clinically significant observations.
Number of subjects with clinically significant observation in physical examination.
Time frame: until 2 weeks after dosing
Frequency is defined as number of subjects with clinically significant observations.
Number of subjects with clinically significant changes in clinical laboratory parameters.
Time frame: until 2 weeks after dosing
Frequency is defined as number of subjects with clinically significant observations.
Number of subjects with clinically significant changes in ECG parameters.
Time frame: until 2 weeks after dosing
ECG parameters include heart rate and PQ, QT, RS. Frequency is defined as number of subjects with clinically significant observations.
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 23 Feb 2021.
- Derived from this study: PubMed 33373732Roch M, Sierra R, Sands K, Martins WMBS, Schrenzel J, Walsh TR, Gales AC, Andrey DO. Vertical and horizontal dissemination of an IncC plasmid harbouring rmtB 16S rRNA methylase gene, conferring resistance to plazomicin, among invasive ST258 and ST16 KPC-producing Klebsiella pneumoniae. J Glob Antimicrob Resist. 2021 Mar;24:183-189. doi: 10.1016/j.jgar.2020.12.006. Epub 2020 Dec 26.
- Individual participant dataSharing planned: No
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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.
Armin Schultz, Dr.med. principal investigator
CRS Clinical Research Services Mannheim GmbH
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 Apramycin injection in people with Healthy Volunteers, run by Juvabis AG 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 8 inclusion and 23 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 23 Feb 2021. 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?
Type and incidence of treatment-emergent adverse events (TEAEs) until 2 weeks after dosing. (time frame: until 2 weeks after dosing). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04105205, which also lists 1 linked publication.
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 23 Feb 2021.