HypercholesterolemiaPhase 1/2NCT02100839
Safety Study of AEM-28 to Treat Refractory Hypercholesterolemia
A Phase 1/2 study testing AEM-28 and Normal Saline in people with Hypercholesterolemia and Hyperlipoproteinemia Type II, run by LipimetiX Development, LLC at 1 site in Australia.
Trial summary
The purpose of the first part of this study is to determine the safety and tolerability of a single dose of AEM-28, an apolipoprotein E mimetic, in subjects with high total cholesterol who are otherwise healthy subjects. The pharmacokinetics and pharmacodynamics of AEM-28 will also be evaluated. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypercholesterolemia, Hyperlipoproteinemia Type II
- What is being tested?
- AEM-28 and Normal Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 52 participants
- Where
- 1 siteAustralia
- Study dates
- Mar 2014to Dec 2014
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Single Ascending Dose (SAD) Study:
- Male or female non-smoker, ≥18 and ≤55 years of age, with BMI >18.5 and < 32.0 kg/m²
- Total cholesterol greater or equal to 5.0 mmol/L (≥194 mg/dL) at screening
- Multiple Ascending Dose (MAD) Study:
- Male or female non-smoker, ≥18 and ≤75 years of age, with BMI >18.5 and < 35.0 kg/m²
- Diagnosis of refractory hypercholesterolemia with LDL cholesterol levels > 2.5 mmol/L (97 mg/mL) at screening.
- On stable lipid lowering therapy for ≥ 8 weeks
- On stable diet for ≥ 12 weeks.
Who cannot join
- SAD Study:
- Any clinically significant abnormality or abnormal laboratory test results found during medical screening or positive test for hepatitis B, hepatitis C, or HIV found during medical screening.
- History of allergic reactions to diphenhydramine, ranitidine, methylprednisone or other related drugs, or history of significant allergic or hypersensitivity reaction (e.g. angioedema) to any substance.
- MAD Study:
- Significant health problems within 6 months prior to screening, which in the opinion of the Medical Sub-Investigator would prevent the subject from participating in the study, including but not limited to: unstable coronary heart disease; transient ischemic attack; stroke; revascularization procedure; uncontrolled hyperthyroidism; coagulation disorder; peptic ulcers or GI bleeding; significant disease of the central nervous system; liver or renal disease.
- History of allergic reactions to diphenhydramine, ranitidine, methylprednisone or other related drugs, or history of significant allergic or hypersensitivity reaction (e.g. angioedema) to any substance.
Trial locations and contacts
1 site in 1 country.
Australia1 site
Linear Clinical Research Ltd.
Nedlands, Western Australia, 6009
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Doses of AEM-28 in Healthy Subjects and Patients With Refractory Hypercholesterolemia
The purpose of the first part of this study is to determine the safety and tolerability of a single dose of AEM-28, an apolipoprotein E mimetic, in subjects with high total cholesterol who are otherwise healthy subjects. The pharmacokinetics and pharmacodynamics of AEM-28 will also be evaluated.
The second part of this study will be a multiple ascending dose evaluation of AEM-28 in patients with refractory hypercholesterolemia.
AEM-28 has demonstrated significant lipid lowering activity and positive effects on the artery wall. AEM-28 is being developed for the treatment of homozygous familial hypercholesterolemia.
- Conditions
- Hypercholesterolemia, Hyperlipoproteinemia Type II
- Being tested
- AEM-28, Normal Saline
- Keywords
- hypercholesterolemia, apolipoprotein E, First in Human, Apolipoprotein E (ApoE), Apolipoprotein E Mimetic (AEM)
- Medical subject headings
- Hypercholesterolemia, Hyperlipoproteinemia Type II
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AEM-28Drug
Also called apolipoprotein E mimetic
Solution for injection
Normal SalineDrug
Also called 0.9% NaCl, Sterile Normal Saline
0.9% saline for injection
| Study group | Role | What they receive |
|---|---|---|
| AEM-28 | Experimental | Single Ascending Dose: Single IV dose for each cohort; dose range 0.032 mg/mL to 3.54 mg/mL
Multiple Ascending Dose: Three (3) IV doses for each cohort, one (1) dose every two (2) weeks; dose range 1 mg/kg to 3.54 mg/kg. Receives: Drug: AEM-28 |
| Normal Saline | Placebo comparator | Single Ascending Dose: Single IV dose for each cohort.
Multiple Ascending Dose: Three (3) IV doses for each cohort, one (1) dose every two (2) weeks. Receives: Drug: Normal Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Who Incurred at Least One Treatment Emergent Event
Safety and tolerability to AEM-28 were evaluated through the assessment of adverse events (i.e., seriousness, severity, relationship to the study medication, outcome, duration, and management), vital signs, 12-lead ECG, telemetry, clinical laboratory parameters, physical examination, and local response to each injection, and body weight (Part B only). Treatment-emergent adverse events were tabulated by treatment. Changes from baseline values in vital signs, ECG, clinical laboratory parameters, physical examination, and body weight (Part B only) were evaluated.
Safety and tolerability data were reported using descriptive statistics.
Measured: Part A (SAD): Day -1 to Day 15; Part B (MAD): Day 1 to Day 57
Number of Participants Who Incurred Mild Treatment Emergent Adverse Events
Safety and tolerability to AEM-28 were evaluated through the assessment of adverse events (i.e., seriousness, severity, relationship to the study medication, outcome, duration, and management), vital signs, 12-lead ECG, telemetry, clinical laboratory parameters, physical examination, and local response to each injection, and body weight (Part B only). Treatment-emergent adverse events were tabulated by treatment. Changes from baseline values in vital signs, ECG, clinical laboratory parameters, physical examination, and body weight (Part B only) were evaluated.
Safety and tolerability data were reported using descriptive statistics.
Measured: Part A (SAD): Day -1 to Day 15; Part B (MAD): Day 1 to Day 57
Number of Participants Who Incurred Moderate Treatment Emergent Events
Safety and tolerability to AEM-28 were evaluated through the assessment of adverse events (i.e., seriousness, severity, relationship to the study medication, outcome, duration, and management), vital signs, 12-lead ECG, telemetry, clinical laboratory parameters, physical examination, and local response to each injection, and body weight (Part B only). Treatment-emergent adverse events were tabulated by treatment. Changes from baseline values in vital signs, ECG, clinical laboratory parameters, physical examination, and body weight (Part B only) were evaluated.
Safety and tolerability data were reported using descriptive statistics.
Measured: Part A (SAD): Day -1 to Day 15; Part B (MAD): Day 1 to Day 57
Secondary outcomes (1)
Very Low Density Lipoprotein Cholesterol (VLDL-C) Percent Change
Maximum observed percentage change in VLDL-C level relative to baseline for all time points measured in Parts A or Part B with highest dose, i.e. 3.54 mg/kg.
Measured: Part A (SAD): Day 1 to Day 15; Part B (MAD): Day 1 to Day 57
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2014 (estimated)
- Study startMar 2014
- Primary completionNov 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HypercholesterolemiaStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- LipimetiX Development, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Janakan Krishnarajah, MBBS, FRACP, Principal investigator, Linear Clinical Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02100839
- Sponsor's protocol ID
- LPMX-112
- Status last verified
- Mar 2015
- First submitted
- 27 Mar 2014
- Last updated
- 29 Dec 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 29 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Doses of AEM-28 in Healthy Subjects and Patients With Refractory Hypercholesterolemia
- ClinicalTrials.gov ID
- NCT02100839
- Acronym / sponsor ID
- LPMX-112
- Conditions
- Hypercholesterolemia, Hyperlipoproteinemia Type II
- Keywords
- hypercholesterolemia, apolipoprotein E, First in Human, Apolipoprotein E (ApoE), Apolipoprotein E Mimetic (AEM)
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- LipimetiX Development, LLCIndustry (pharma, biotech, devices)
- Study start
- Mar 2014
- Primary completion
- Nov 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 1 Apr 2014 (estimated)
- Results
- Posted 29 Dec 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the first part of this study is to determine the safety and tolerability of a single dose of AEM-28, an apolipoprotein E mimetic, in subjects with high total cholesterol who are otherwise healthy subjects. The pharmacokinetics and pharmacodynamics of AEM-28 will also be evaluated.
The second part of this study will be a multiple ascending dose evaluation of AEM-28 in patients with refractory hypercholesterolemia.
AEM-28 has demonstrated significant lipid lowering activity and positive effects on the artery wall. AEM-28 is being developed for the treatment of homozygous familial hypercholesterolemia.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AEM-28 | Experimental | Drug: AEM-28Single Ascending Dose: Single IV dose for each cohort; dose range 0.032 mg/mL to 3.54 mg/mL Multiple Ascending Dose: Three (3) IV doses for each cohort, one (1) dose every two (2) weeks; dose range 1 mg/kg to 3.54 mg/kg. |
| Normal Saline | Placebo comparator | Drug: Normal SalineSingle Ascending Dose: Single IV dose for each cohort. Multiple Ascending Dose: Three (3) IV doses for each cohort, one (1) dose every two (2) weeks. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male or female non-smoker, ≥18 and ≤55 years of age, with BMI >18.5 and < 32.0 kg/m²
- Total cholesterol greater or equal to 5.0 mmol/L (≥194 mg/dL) at screening
- Male or female non-smoker, ≥18 and ≤75 years of age, with BMI >18.5 and < 35.0 kg/m²
- Diagnosis of refractory hypercholesterolemia with LDL cholesterol levels > 2.5 mmol/L (97 mg/mL) at screening.
- On stable lipid lowering therapy for ≥ 8 weeks
Key exclusion criteria (6 listed)
- Any clinically significant abnormality or abnormal laboratory test results found during medical screening or positive test for hepatitis B, hepatitis C, or HIV found during medical screening.
- History of allergic reactions to diphenhydramine, ranitidine, methylprednisone or other related drugs, or history of significant allergic or hypersensitivity reaction (e.g. angioedema) to any substance.
- Significant health problems within 6 months prior to screening, which in the opinion of the Medical Sub-Investigator would prevent the subject from participating in the study, including but not limited to: unstable coronary heart disease; transient ischemic attack; stroke; revascularization procedure; uncontrolled hyperthyroidism; coagulation disorder; peptic ulcers or GI bleeding; significant disease of the central nervous system; liver or renal disease.
- History of allergic reactions to diphenhydramine, ranitidine, methylprednisone or other related drugs, or history of significant allergic or hypersensitivity reaction (e.g. angioedema) to any substance.
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 |
|---|---|---|
| AEM-28Also: apolipoprotein E mimeticSolution for injection | Drug | AEM-28 |
| Normal SalineAlso: 0.9% NaCl, Sterile Normal Saline0.9% saline for injection | Drug | Normal Saline |
Primary outcome
Number of Participants Who Incurred at Least One Treatment Emergent Event
Time frame: Part A (SAD): Day -1 to Day 15; Part B (MAD): Day 1 to Day 57
Safety and tolerability to AEM-28 were evaluated through the assessment of adverse events (i.e., seriousness, severity, relationship to the study medication, outcome, duration, and management), vital signs, 12-lead ECG, telemetry, clinical laboratory parameters, physical examination, and local response to each injection, and body weight (Part B only). Treatment-emergent adverse events were tabulated by treatment. Changes from baseline values in vital signs, ECG, clinical laboratory parameters, physical examination, and body weight (Part B only) were evaluated. Safety and tolerability data were reported using descriptive statistics.
Number of Participants Who Incurred Mild Treatment Emergent Adverse Events
Time frame: Part A (SAD): Day -1 to Day 15; Part B (MAD): Day 1 to Day 57
Safety and tolerability to AEM-28 were evaluated through the assessment of adverse events (i.e., seriousness, severity, relationship to the study medication, outcome, duration, and management), vital signs, 12-lead ECG, telemetry, clinical laboratory parameters, physical examination, and local response to each injection, and body weight (Part B only). Treatment-emergent adverse events were tabulated by treatment. Changes from baseline values in vital signs, ECG, clinical laboratory parameters, physical examination, and body weight (Part B only) were evaluated. Safety and tolerability data were reported using descriptive statistics.
Number of Participants Who Incurred Moderate Treatment Emergent Events
Time frame: Part A (SAD): Day -1 to Day 15; Part B (MAD): Day 1 to Day 57
Safety and tolerability to AEM-28 were evaluated through the assessment of adverse events (i.e., seriousness, severity, relationship to the study medication, outcome, duration, and management), vital signs, 12-lead ECG, telemetry, clinical laboratory parameters, physical examination, and local response to each injection, and body weight (Part B only). Treatment-emergent adverse events were tabulated by treatment. Changes from baseline values in vital signs, ECG, clinical laboratory parameters, physical examination, and body weight (Part B only) were evaluated. Safety and tolerability data were reported using descriptive statistics.
1 secondary outcome
Very Low Density Lipoprotein Cholesterol (VLDL-C) Percent Change
Time frame: Part A (SAD): Day 1 to Day 15; Part B (MAD): Day 1 to Day 57
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Dec 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Janakan Krishnarajah, MBBS, FRACP principal investigator
Linear Clinical Research
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing AEM-28 and Normal Saline in people with Hypercholesterolemia and Hyperlipoproteinemia Type II, run by LipimetiX Development, LLC at 1 site in Australia.
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 6 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 29 Dec 2015. 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 Australia. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Dec 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants Who Incurred at Least One Treatment Emergent Event (time frame: Part A (SAD): Day -1 to Day 15; Part B (MAD): Day 1 to Day 57). The study lists 3 primary outcomes in all. 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 29 Dec 2015.