GOLDILOX: Efficacy and Safety of MEDI6570 in Patients With a History of Myocardial Infarction

Sponsor

AstraZeneca (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04610892

Collaborator

Thrombolysis in Myocardial Infarction (TIMI) Study Group (Other)

400

Enrollment

Locations

Arms

35.6

Anticipated Duration (Months)

4.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A Phase IIB Parallel group Study to Evaluate the Efficacy and Safety of MEDI6570 in Participants with a Prior Myocardial Infarction.

Condition or Disease	Intervention/Treatment	Phase
Coronary Heart Disease (CHD)	Biological: MEDI6570 Biological: Placebo	Phase 2

Detailed Description

This Phase IIB, proof-of-concept, dose-range finding clinical study is being conducted to evaluate the anti-inflammatory potential of MEDI6570 and its effect on surrogates for atherosclerotic and heart failure (HF) events in patients with a history of myocardial infarction (MI). The results of the Phase IIB study will inform future clinical development options and precision medicine strategy for future clinical studies.

Participants will be randomized in a 2:2:1:1 ratio after protocol Amend 2, 360 evaluable participants (111 evaluable participants in each of the 2 MEDI6570 groups, plus 27 evaluable participants in the legacy low dose MEDI6570 group, plus 111 participants in pooled placebo) will complete the study.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

400 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Phase IIB, Randomized, Double Blinded, Placebo Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of MEDI6570 in Participants With a Prior Myocardial Infarction and Persistent Inflammation

Actual Study Start Date :

Nov 4, 2020

Anticipated Primary Completion Date :

Oct 24, 2023

Anticipated Study Completion Date :

Oct 24, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MEDI6570 Low dose Monthly Subcutaneous administration.	Biological: MEDI6570 MEDI6570
Experimental: MEDI6570 Medium dose Monthly Subcutaneous administration.	Biological: MEDI6570 MEDI6570
Experimental: MEDI6570 High dose Monthly Subcutaneous administration.	Biological: MEDI6570 MEDI6570
Placebo Comparator: Placebo Low dose Monthly Subcutaneous administration.	Biological: Placebo Buffer
Placebo Comparator: Placebo Medium dose Monthly Subcutaneous administration	Biological: Placebo Buffer
Placebo Comparator: Placebo High dose Monthly Subcutaneous administration	Biological: Placebo Buffer

Outcome Measures

Primary Outcome Measures

Non Calcified Plaque Volume [9 months]
Change in non-calcified plaque volume in the most diseased coronary segment (NCPVMD), as measured by CTA imaging compared to placebo.

Secondary Outcome Measures

NT proBNP [9 months]
Change in NT proBNP compared to placebo
LVEF [9 months]
Change in LVEF as measured by echocardiography compared to placebo
Global Longitudinal Strain (GLS) [9 months]
Change in GLS as measured by echocardiography compared to placebo
Global non-calcified plaque volume [9 months]
Change in Global non-calcified plaque volume as measured by CTA imaging compared to placebo
Low attenuation plaque volume [9 months]
Change in Low attenuation plaque volume as measured by CTA imaging compared to placebo
Adverse Events as a measure of safety and tolerability of MEDI6570 [13.5 months]
Incidence of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) compared to placebo
Adverse events as a measure of safety and tolerability of MEDI6570 [13.5 months]
Adverse events (AEs) as evaluated by incidence of clinically important changes in vital signs, ECG, chemistry, or hematology values compared to placebo
Incidence Rate of Immunogenicity [13.5 months]
Immunogenicity as measured by anti-drug antibodies (ADAs)
Pharmacokinetics of MEDI6570 Cmax [13.5 months]
Non-compartmental analysis will be performed for MEDI6570 treated subjects
Pharmacokinetics of MEDI6570 Terminal Half-life [13.5 months]
Non-compartmental analysis will be performed for MEDI6570 treated subjects
LVEF [9 months]
Change in LVEF as measured by echocardiography among participants with reduced ejection fraction compared to placebo
Global Longitudinal Strain (GLS) [9 months]
Change in GLS as measured by echocardiography among participants with reduced ejection fraction compared to placebo
ADA titer [13.5 months]
Immunogenicity as measured by anti-drug antibodies (ADAs)

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Participant must provide informed consent before any study specific activities are performed, must be able and willing to meet all requirements for randomization within 42 days after signing the full ICF, and must adhere to the schedules of activities.
Women must be ≥ 40 years of age at the time of signing the ICF. Men must be ≥ 21 years of age at the time of signing the ICF.
Participant must:
be 30 to 365 days after presumed type-1 (ie, due to plaque rupture or erosion) MI (either STEMI or NSTEMI) at the time of enrollment.
have persistent inflammation, defined as hs CRP ≥ 1 mg/L, as measured centrally at screening Visit 1.
Participant must have body mass index within the range 18 to 40 kg/m2 inclusive.
For female participants, the participant must not be pregnant or lactating and must be of non-childbearing potential, confirmed at screening Visit 1 by one of the following:
Postmenopausal, defined as amenorrhea for ≥ 12 months following cessation of all exogenous hormonal treatments, and with luteinizing hormone and follicle stimulating hormone levels in the postmenopausal range.
Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy. Tubal ligation is not considered as irreversible surgical sterilization.
Participant must have an evaluable, pre-randomization CTA with quantifiable, non calcified plaque.

Exclusion Criteria:

History of any clinically important disease or disorder which, in the opinion of the investigator, may either put the participant at risk because of participation in the study, or influence the results or the participant's ability to participate in the study.
Percutaneous coronary intervention or diagnostic angiogram planned after screening. Eligible participants who have a diagnostic angiogram performed in the absence of undergoing a new PCI may continue screening after the diagnostic angiogram has been performed or may be rescreened.
History of or planned coronary artery bypass grafting.
Documented episode of post-MI pericarditis in the 3 months before enrollment.
Ongoing New York Heart Association Class IV HF.
Increased risk of bleeding
Patients with history or presence of any bleeding disorder.
Signs of ongoing bleeding at screening (eg, identified macroscopic bleeding, low hemoglobin presumed to be caused by bleeding) or high risk for major bleeding in accordance with the Investigator's assessment.
Need for chronic therapeutic anticoagulation therapy anticipated to be required throughout the course of the study (short-term treatment with prophylactic doses of heparin/low molecular weight heparin are allowed).
Known severe liver disease.
History or presence of any of the following:
Ongoing infection or febrile illness that in the opinion of the investigator may be the cause of elevated hs-CRP on screening.
Ongoing atrial fibrillation or flutter.
Cancer within 5 years before randomization, with the exception of non melanoma skin cancer.
Alcohol or substance abuse within 6 months before randomization, as judged by the investigator.
Known history of hypersensitivity reactions to other biologics, to human IgG preparations, or to any component of MEDI6570, or ongoing severe allergy as judged by the investigator.
Patients with active positive results on screening for serum hepatitis B surface antigen, hepatitis C antibody, or HIV.
Any clinically important abnormalities in clinical chemistry, hematology, coagulation parameters, as judged by the investigator.
BP values at screening:
Systolic BP < 90 mmHg or > 180 mmHg.
Diastolic BP > 100 mmHg.
Participants who are excluded based on elevated BP may be rescreened following adequate treatment.
Participants with any of the following contraindications to CTA:
eGFR < 50 mL/min/1.73 m2 by the Chronic Kidney Disease Epidemiology Collaboration equation, or end stage renal disease treated with kidney transplant or renal replacement therapy.
Allergy to iodinated contrast.
History of contrast-induced nephropathy.
Contraindication to nitroglycerin.
Rapid heart rate that is uncontrolled by medical therapy.
Inability to hold breath for at least 6 seconds.
Receipt of any investigational device or therapy within 6 months or 5 half lives before screening (whichever is longer).

This criterion does NOT apply for inactive, non replicating COVID-19 vaccines approved by Health Authorities or under emergency use authorization.

Planned participation in an additional investigational study of an intervention or biologic before the end of the follow-up period. Participation in observational studies or studies without investigational drugs or devices is allowed.
Participants who are legally institutionalized.
An employee or close relative of an employee of the sponsor, the CRO, or the study site, regardless of the employee or close relative's role.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Mobile	Alabama	United States	36608
2	Research Site	Beverly Hills	California	United States	90211
3	Research Site	Covina	California	United States	91723
4	Research Site	Northridge	California	United States	91324
5	Research Site	Northridge	California	United States	91325-4139
6	Research Site	Torrance	California	United States	90502
7	Research Site	Jacksonville	Florida	United States	32216
8	Research Site	Ponte Vedra	Florida	United States	32081
9	Research Site	Decatur	Georgia	United States	30033
10	Research Site	Muncie	Indiana	United States	47303
11	Research Site	Richmond	Indiana	United States	47374
12	Research Site	Ames	Iowa	United States	50010
13	Research Site	West Des Moines	Iowa	United States	50266
14	Research Site	Midland	Michigan	United States	48640
15	Research Site	Columbia	Missouri	United States	65212
16	Research Site	Lincoln	Nebraska	United States	68506
17	Research Site	New Brunswick	New Jersey	United States	08901
18	Research Site	Buffalo	New York	United States	14221
19	Research Site	Canton	Ohio	United States	44710
20	Research Site	Rapid City	South Dakota	United States	57701
21	Research Site	Winchester	Virginia	United States	22601
22	Research Site	Madison	Wisconsin	United States	53792
23	Research Site	Adelaide		Australia	5000
24	Research Site	Bedford Park		Australia	5042
25	Research Site	Clayton		Australia	VIC 3168
26	Research Site	Epping		Australia	3076
27	Research Site	Herston		Australia	4029
28	Research Site	Murdoch		Australia	WA6150
29	Research Site	Perth		Australia	WA 6000
30	Research Site	Vancouver	British Columbia	Canada	V5Z 1M9
31	Research Site	Ottawa	Ontario	Canada	K1Y 4W7
32	Research Site	Toronto	Ontario	Canada	M5G 2C4
33	Research Site	Montreal	Quebec	Canada	H1T 1C8
34	Research Site	Brno		Czechia	656 91
35	Research Site	Hradec Králové		Czechia	500-05
36	Research Site	Liberec		Czechia	46002
37	Research Site	Pardubice		Czechia	532 03
38	Research Site	Plzen - Bory		Czechia	305 99
39	Research Site	Praha 5		Czechia	150 06
40	Research Site	Budapest		Hungary	1133
41	Research Site	Budapest		Hungary	1134
42	Research Site	Budapest		Hungary	H-1122
43	Research Site	Debrecen		Hungary	4032
44	Research Site	Székesfehérvár		Hungary	8000
45	Research Site	Cona		Italy	44124
46	Research Site	Milan		Italy	20138
47	Research Site	Parma		Italy	43126
48	Research Site	Rozzano		Italy	20089
49	Research Site	Himeji-shi		Japan	670-0981
50	Research Site	Kasuga-shi		Japan	816-0864
51	Research Site	Kasugai-shi		Japan	487-0016
52	Research Site	Kitakyushu-shi		Japan	802-8555
53	Research Site	Kumamoto-shi		Japan	860-0008
54	Research Site	Kyoto-shi		Japan	606-8507
55	Research Site	Matsudo-Shi		Japan	271-0077
56	Research Site	Minami-ku		Japan	861-4193
57	Research Site	Miyazaki-shi		Japan	880-0834
58	Research Site	Morioka-shi		Japan	020-0066
59	Research Site	Osaka-shi		Japan	558-8558
60	Research Site	Sendai-shi		Japan	980-0873
61	Research Site	Alkmaar		Netherlands	1814 HB
62	Research Site	Deventer		Netherlands	7416 SE
63	Research Site	Heerlen		Netherlands	6419 PC
64	Research Site	Nijmegen		Netherlands	6525 GA
65	Research Site	Nijmegen		Netherlands	6532 SZ
66	Research Site	Tilburg		Netherlands	5042AD
67	Research Site	Utrecht		Netherlands	3508 AB
68	Research Site	Venlo		Netherlands	5912 BL
69	Research Site	Zwolle		Netherlands	8025 AB
70	Research Site	Bialystok		Poland	15-276
71	Research Site	Bydgoszcz		Poland	85-095
72	Research Site	Gdynia		Poland	81-423
73	Research Site	Katowice		Poland	40-635
74	Research Site	Krakow		Poland	31-202
75	Research Site	Kraków		Poland	30-082
76	Research Site	Kraków		Poland	30-688
77	Research Site	Opole		Poland	45-401
78	Research Site	Wroclaw		Poland	50-556
79	Research Site	Kazan		Russian Federation	420101
80	Research Site	Moscow		Russian Federation	121309
81	Research Site	Saint Petersburg		Russian Federation	192242
82	Research Site	Saint Petersburg		Russian Federation	193312
83	Research Site	Saratov		Russian Federation	410012
84	Research Site	Barcelona		Spain	08003
85	Research Site	El Palmar		Spain	30120
86	Research Site	Hospitalet de Llobregat(Barcel		Spain	08907
87	Research Site	Madrid		Spain	28040
88	Research Site	Madrid		Spain	28046
89	Research Site	Pontevedra		Spain	36312
90	Research Site	Santiago de Compostela		Spain	15706
91	Research Site	Sevilla		Spain	41009
92	Research Site	Exeter		United Kingdom	EX2 5DW
93	Research Site	High Wycombe		United Kingdom	HP11 2TT
94	Research Site	Liverpool		United Kingdom	L14 3PE
95	Research Site	Middlesborough		United Kingdom	TS4 3BW
96	Research Site	Newcastle upon Tyne		United Kingdom	NE7 7DN
97	Research Site	Oxford		United Kingdom	OX3 7LJ
98	Research Site	Wythenshawe		United Kingdom	M23 9LT