AtherosclerosisPhase 1NCT03654313
Single and Multiple Ascending Doses of MEDI6570 in Subjects With Type 2 Diabetes Mellitus
A Phase 1 study testing MEDI6570 in people with Atherosclerosis and Cardiovascular Disease, run by MedImmune LLC at 9 sites in United States.
Trial summary
To evaluate the safety, tolerability, PK and immunogenicity of single and multiple ascending doses of MEDI6570 in subjects with Type 2 Diabetes Mellitus Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Atherosclerosis, Cardiovascular Disease
- What is being tested?
- MEDI6570
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 88 participants
- Where
- 9 sitesUnited States
- Study dates
- 28 Sep 2018to 21 Jul 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- In Part A, subjects aged 18 through 65 inclusive at screening. In Part B, male subjects aged 18 through 65 inclusive, and female subjects aged 40 to 65 inclusive, at screening.
- Body mass index of 18 to 45 kg/m2.
- Subjects with T2DM on stable medical therapy for at least 6 weeks prior to screening with no clinically significant dose change and/or new medications in the recent 6 weeks
- Capable of giving written informed consent and adhere to visit/protocol schedule
- Female subjects must be of non-childbearing potential, confirmed at screening by one of the following: (a) Postmenopausal, defined as amenorrhea for ≥ 12 months following cessation of all exogenous hormonal treatments, and luteinizing hormone and follicle stimulating hormone (FSH) levels in the postmenopausal range. (b) Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy. Tubal ligation is not considered as irreversible surgical sterilization.
- Non-sterilized male subjects who are sexually active with a female partner of childbearing potential must use a male condom plus spermicide, and in addition the female partner must use 1 highly effective method of contraception.
- In Part B, subjects must meet CTA criteria as follows: (Estimated glomular filtration rate (eGFR) ≥ 60 mL/min/1.73m2. No allergy to iodinated contrast, no history of contrast induced nephropathy or no contraindication to beta blockers or nitroglycerin. No recent pulmonary embolism and must able to hold breath for at least 6 seconds. No history of coronary bypass surgery and no active arrhythmia on day of CTA scan (atrial fibrillation, atrial flutter, frequent premature atrial, or ventricular contractions).
- For Part A Cohort 6, subjects must be Japanese (eg, natives of Japan or Japanese Americans), defined as having both parents and four grandparents who are Japanese. This includes second and third generation subjects of Japanese descent whose parents or grandparents are living in a country other than Japan.
Who cannot join
- History of any clinically important disease or disorder (not including T2DM) which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.
- History or presence of hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs.
- Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of investigational product, or planned surgical procedure before study completion.
- Female subjects who are pregnant and/or currently lactating.
- Any clinically important abnormalities in clinical chemistry, hematology, coagulation parameters, or urinalysis results -History of blood dyscrasia, hemostatic disorder, systemic bleeding, or prior trauma that places the subject at a higher risk of bleeding.
- History of vascular abnormalities including aneurysms, prior dissections; hx of severe hemorrhage, hematemesis, melena, haemoptysis, severe epistaxis, severe thrombocytopenia, intracranial hemorrhage, rectal bleeding, or major surgery/procedure within 3 months prior to Visit 1; a history suggestive of active peptic ulcer disease; or prior intracranial haemorrhage. -Dual-antiplatelet therapy, anticoagulation therapy or thrombolytic use, in the past month or planned use during the duration of the study. -Chronic aspirin therapy or chronic NSAID therapy.
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- Clinically significant ECG that may interfere with the interpretation of serial ECG and QT interval changes screening. -Persistent or intermittent complete bundle branch block, incomplete bundle branch block, or intraventricular conduction delay with QRS > 110 ms. Subjects with QRS > 110 ms but < 115 ms are acceptable if there is no evidence of ventricular hypertrophy or pre excitation. -Abnormal vital signs
- Hemoglobin A1c>9.0% measured at screening. HbA1c can be retested once after approximately 4 weeks.
- Clinically significant late diabetic complications including symptoms consistent with angina, congestive heart failure, and peripheral arterial disease (claudication), or other complications such as proliferative retinopathy, maculopathy, or gastroparesis.
- Any positive result at screening for serum hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus (HIV).
- History of cancer in the last 5 years, with the exception of non-melanoma skin cancer. -History of alcohol substance abuse within the past 6 months. A positive drug screen including recreational marijuana will be exclusionary. However, subjects with a documented medical need or prescription may be included at the discretion of the principal investigator.
- History of hypersensitivity or ongoing severe allergy or history of hypersensitivity to drugs with a similar chemical structure or calss to MEDI6570.
- History of ongoing infection or febrile illness within 30 days prior to Day 1.
- Current or previous use of systemic corticosteroids within 28 days prior to screening.
- Receipt of any investigational product or use of any biologics within 6 months or 5 half lives prior to screening (whichever is longer), or planned participation in an additional study of an investigational product therapy or biologic prior to end of follow up period.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
Research Site
Anniston, Alabama, 36207
Research Site
Cincinnati, Ohio, 45227
Research Site
High Point, North Carolina, 27265
Research Site
Honolulu, Hawaii, 96814
Research Site
Jacksonville, Florida, 32216
Research Site
Knoxville, Tennessee, 37920
Research Site
Miami, Florida, 33143
Research Site
Port Orange, Florida, 32127
Research Site
San Antonio, Texas, 78229
About this study
Official title: A Phase 1 Randomized, Blinded, Placebo-controlled Study to Evaluate the Safety and Pharmacokinetics of Single and Multiple Ascending Doses of MEDI6570 in Subjects With Type 2 Diabetes Mellitus.
To evaluate the safety, tolerability, PK and immunogenicity of single and multiple ascending doses of MEDI6570 in subjects with Type 2 Diabetes Mellitus
Read the detailed description
A Phase 1 Randomized, Blinded, Placebo-controlled Study to Evaluate the Safety and Pharmacokinetics of Single and Multiple Ascending Doses of MEDI6570 in Subjects with Type 2 Diabetes Mellitus
- Conditions
- Atherosclerosis, Cardiovascular Disease
- Being tested
- MEDI6570, Placebo, Part B Placebo
- Keywords
- Atherosclerosis, Cardiovascular Disease, CAD, Atherosclerotic Cardiovascular Disease
- Medical subject headings
- Atherosclerosis, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MEDI6570Biological
MEDI6570
PlaceboBiological
Placebo
Part B PlaceboBiological
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Part A MEDI6570 Cohort 1 | Experimental | Part A MEDI6570 Cohort 1 dose level Receives: Biological: MEDI6570 |
| Part A MEDI6570 Cohort 2 | Experimental | Part A MEDI6570 Cohort 2 dose level Receives: Biological: MEDI6570 |
| Part A MEDI6570 Cohort 3 | Experimental | Part A MEDI6570 Cohort 3 dose level Receives: Biological: MEDI6570 |
| Part A MEDI6570 Cohort 4 | Experimental | Part A MEDI6570 Cohort 4 dose level Receives: Biological: MEDI6570 |
| Part A Placebo | Placebo comparator | Part A Placebo Receives: Biological: Placebo |
| Part B MEDI6570 Cohort 1 | Experimental | Part B MEDI6570 Cohort 1 dose level Receives: Biological: MEDI6570 |
| Part B MEDI6570 Cohort 2 | Experimental | Part B MEDI6570 Cohort 2 dose level Receives: Biological: MEDI6570 |
| Part B MEDI6570 Cohort 3 | Experimental | Part B MEDI6570 Cohort 3 dose level Receives: Biological: MEDI6570 |
| Part B Placebo | Placebo comparator | Part B Placebo Receives: Biological: Part B Placebo |
| Part A MEDI6570 Cohort 5 | Experimental | Part A MEDI6570 Cohort 5 Dose level Receives: Biological: MEDI6570 |
| Part A MEDI6570 Cohort 6 | Experimental | Part A MEDI6570 Cohort 6 dose level Receives: Biological: MEDI6570 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of subjects with adverse events and serious adverse events as a measure of safety and tolerability of MEDI6570
Measured by the incidence of treatment- emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs)
Measured: Day 1 - Day 190 (Part A); Day 1 - Day 250 (Part B)
Secondary outcomes (5)
Pharmacokinetics of MEDI6570 AUC
Non-compartmental analysis will be performed for MEDI6570 treated subjects. Descriptive statistics for PK parameters will be provided
Measured: Day 1 - Day 190 (Part A); Day 1 - Day 250 (Part B)
Pharmacokinetics of MEDI6570 Cmax
Non-compartmental analysis will be performed for MEDI6570 treated subjects. Descriptive statistics for PK parameters will be provided
Measured: Day 1 - Day 190 (Part A); Day 1 - Day 250 (Part B)
Pharmacokinetics of MEDI6570 Tmax
Non-compartmental analysis will be performed for MEDI6570 treated subjects. Descriptive statistics for PK parameters will be provided
Measured: Day 1 - Day 190 (Part A); Day 1 - Day 250 (Part B)
Pharmacokinetics of MEDI6570 Terminal Half life
Non-compartmental analysis will be performed for MEDI6570 treated subjects. Descriptive statistics for PK parameters will be provided
Measured: Day 1 - Day 190 (Part A); Day 1 - Day 250 (Part B)
Immunogenicity rate
ADA incidence rate and titer will be tabulated for each treatment group. Samples confirmed positive for ADA will be tested and analyzed for nAB titer and summarized similarly.
Measured: Day 1 - Day 190 (Part A); Day 1 - Day 250 (Part B)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2018
- Study start28 Sep 2018
- Primary completion21 Jul 2020
- Study completion21 Jul 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 AtherosclerosisStudies 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 88 participants (actual)
Sponsor and investigators
- Lead sponsor
- MedImmune LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Marvin Sinsakul, Study director, MedImmune LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03654313
- Sponsor's protocol ID
- D4920C00001
- Status last verified
- Aug 2020
- First submitted
- 29 Aug 2018
- Last updated
- 24 Aug 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Publications
Vavere AL, Sinsakul M, Ongstad EL, Yang Y, Varma V, Jones C, Goodman J, Dubois VFS, Quartino AL, Karathanasis SK, Abuhatzira L, Collen A, Antoniades C, Koren MJ, Gupta R, George RT. Lectin-Like Oxidized Low-Density Lipoprotein Receptor 1 Inhibition in Type 2 Diabetes: Phase 1 Results. J Am Heart Assoc. 2023 Feb 7;12(3):e027540. doi: 10.1161/JAHA.122.027540. Epub 2023 Jan 23.
PubMed 36688371
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Randomized, Blinded, Placebo-controlled Study to Evaluate the Safety and Pharmacokinetics of Single and Multiple Ascending Doses of MEDI6570 in Subjects With Type 2 Diabetes Mellitus.
- ClinicalTrials.gov ID
- NCT03654313
- Acronym / sponsor ID
- D4920C00001
- Conditions
- Atherosclerosis, Cardiovascular Disease
- Keywords
- Atherosclerosis, Cardiovascular Disease, CAD, Atherosclerotic Cardiovascular Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 88 participants (actual)
- Lead sponsor
- MedImmune LLCIndustry (pharma, biotech, devices)
- Study start
- 28 Sep 2018 (actual)
- Primary completion
- 21 Jul 2020 (actual)
- Study completion
- 21 Jul 2020 (actual)
- First posted
- 31 Aug 2018 (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.
To evaluate the safety, tolerability, PK and immunogenicity of single and multiple ascending doses of MEDI6570 in subjects with Type 2 Diabetes Mellitus
Detailed description
A Phase 1 Randomized, Blinded, Placebo-controlled Study to Evaluate the Safety and Pharmacokinetics of Single and Multiple Ascending Doses of MEDI6570 in Subjects with Type 2 Diabetes Mellitus
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 11
| Arm | Type | Receives |
|---|---|---|
| Part A MEDI6570 Cohort 1 | Experimental | Biological: MEDI6570Part A MEDI6570 Cohort 1 dose level |
| Part A MEDI6570 Cohort 2 | Experimental | Biological: MEDI6570Part A MEDI6570 Cohort 2 dose level |
| Part A MEDI6570 Cohort 3 | Experimental | Biological: MEDI6570Part A MEDI6570 Cohort 3 dose level |
| Part A MEDI6570 Cohort 4 | Experimental | Biological: MEDI6570Part A MEDI6570 Cohort 4 dose level |
| Part A Placebo | Placebo comparator | Biological: PlaceboPart A Placebo |
| Part B MEDI6570 Cohort 1 | Experimental | Biological: MEDI6570Part B MEDI6570 Cohort 1 dose level |
| Part B MEDI6570 Cohort 2 | Experimental | Biological: MEDI6570Part B MEDI6570 Cohort 2 dose level |
| Part B MEDI6570 Cohort 3 | Experimental | Biological: MEDI6570Part B MEDI6570 Cohort 3 dose level |
| Part B Placebo | Placebo comparator | Biological: Part B PlaceboPart B Placebo |
| Part A MEDI6570 Cohort 5 | Experimental | Biological: MEDI6570Part A MEDI6570 Cohort 5 Dose level |
| Part A MEDI6570 Cohort 6 | Experimental | Biological: MEDI6570Part A MEDI6570 Cohort 6 dose level |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- In Part A, subjects aged 18 through 65 inclusive at screening. In Part B, male subjects aged 18 through 65 inclusive, and female subjects aged 40 to 65 inclusive, at screening.
- Body mass index of 18 to 45 kg/m2.
- Subjects with T2DM on stable medical therapy for at least 6 weeks prior to screening with no clinically significant dose change and/or new medications in the recent 6 weeks
- Capable of giving written informed consent and adhere to visit/protocol schedule
- Female subjects must be of non-childbearing potential, confirmed at screening by one of the following: (a) Postmenopausal, defined as amenorrhea for ≥ 12 months following cessation of all exogenous hormonal treatments, and luteinizing hormone and follicle stimulating hormone (FSH) levels in the postmenopausal range. (b) Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy. Tubal ligation is not considered as irreversible surgical sterilization.
Key exclusion criteria (15 listed)
- History of any clinically important disease or disorder (not including T2DM) which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.
- History or presence of hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs.
- Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of investigational product, or planned surgical procedure before study completion.
- Female subjects who are pregnant and/or currently lactating.
- Any clinically important abnormalities in clinical chemistry, hematology, coagulation parameters, or urinalysis results -History of blood dyscrasia, hemostatic disorder, systemic bleeding, or prior trauma that places the subject at a higher risk of bleeding.
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 |
|---|---|---|
| MEDI6570MEDI6570 | Biological | Part A MEDI6570 Cohort 1, Part A MEDI6570 Cohort 2, Part A MEDI6570 Cohort 3, Part A MEDI6570 Cohort 4, Part A MEDI6570 Cohort 5, Part A MEDI6570 Cohort 6, Part B MEDI6570 Cohort 1, Part B MEDI6570 Cohort 2, Part B MEDI6570 Cohort 3 |
| PlaceboPlacebo | Biological | Part A Placebo |
| Part B PlaceboPlacebo | Biological | Part B Placebo |
Primary outcome
Number of subjects with adverse events and serious adverse events as a measure of safety and tolerability of MEDI6570
Time frame: Day 1 - Day 190 (Part A); Day 1 - Day 250 (Part B)
Measured by the incidence of treatment- emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs)
5 secondary outcomes
Pharmacokinetics of MEDI6570 AUC
Time frame: Day 1 - Day 190 (Part A); Day 1 - Day 250 (Part B)
Pharmacokinetics of MEDI6570 Cmax
Time frame: Day 1 - Day 190 (Part A); Day 1 - Day 250 (Part B)
Pharmacokinetics of MEDI6570 Tmax
Time frame: Day 1 - Day 190 (Part A); Day 1 - Day 250 (Part B)
Pharmacokinetics of MEDI6570 Terminal Half life
Time frame: Day 1 - Day 190 (Part A); Day 1 - Day 250 (Part B)
Immunogenicity rate
Time frame: Day 1 - Day 190 (Part A); Day 1 - Day 250 (Part B)
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 24 Aug 2020.
- Derived from this study: PubMed 36688371Vavere AL, Sinsakul M, Ongstad EL, Yang Y, Varma V, Jones C, Goodman J, Dubois VFS, Quartino AL, Karathanasis SK, Abuhatzira L, Collen A, Antoniades C, Koren MJ, Gupta R, George RT. Lectin-Like Oxidized Low-Density Lipoprotein Receptor 1 Inhibition in Type 2 Diabetes: Phase 1 Results. J Am Heart Assoc. 2023 Feb 7;12(3):e027540. doi: 10.1161/JAHA.122.027540. Epub 2023 Jan 23.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
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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.
Marvin Sinsakul study director
MedImmune LLC
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MEDI6570 in people with Atherosclerosis and Cardiovascular Disease, run by MedImmune LLC at 9 sites in United States.
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 15 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 24 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States. 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?
Number of subjects with adverse events and serious adverse events as a measure of safety and tolerability of MEDI6570 (time frame: Day 1 - Day 190 (Part A); Day 1 - Day 250 (Part B)). 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 NCT03654313, 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 24 Aug 2020.