Clinical Trials Register

Summary
EudraCT Number:	2018-003811-23
Sponsor's Protocol Code Number:	IMG-7289-CTP-102
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2019-11-07
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2018-003811-23

A.3

Full title of the trial

A Multi-Center, Open Label Study to Assess the Safety, Steady-State Pharmacokinetics and Pharmacodynamics of IMG-7289 in Patients with Myelofibrosis.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A study to test the safety and effects of IMG-7289 in patients with myelofibrosis.

A.3.2

Name or abbreviated title of the trial where available

IMG-7289-CTP-102 Phase 2b expansion

A.4.1

Sponsor's protocol code number

IMG-7289-CTP-102

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT03136185

A.5.4

Other Identifiers

Name:	IND	Number:	130,789
Name:	INN	Number:	bomedemstat

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Imago BioSciences Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Imago BioSciences, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Imago BioSciences Ltd.
B.5.2	Functional name of contact point	Amber Jones
B.5.3	Address:
B.5.3.1	Street Address	The Bryn
B.5.3.2	Town/ city	Redwick
B.5.3.3	Post code	NP26 3DE
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	07780113652
B.5.6	E-mail	amber@imagobio.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/16/1757
D.3 Description of the IMP
D.3.1	Product name	IMG-7289
D.3.2	Product code	IMG-7289
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	bomedemstat
D.3.9.1	CAS number	1990504-34-1
D.3.9.2	Current sponsor code	IMG-7289
D.3.9.4	EV Substance Code	AS2
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	bomedemstat
D.3.9.1	CAS number	1990504-34-1
D.3.9.2	Current sponsor code	IMG-7289
D.3.9.4	EV Substance Code	AS3
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	bomedemstat
D.3.9.1	CAS number	1990504-34-1
D.3.9.2	Current sponsor code	IMG-7289
D.3.9.4	EV Substance Code	AS4
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	bomedemstat
D.3.9.1	CAS number	1990504-34-1
D.3.9.2	Current sponsor code	IMG-7289
D.3.9.4	EV Substance Code	AS5
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Patients with myelofibrosis including primary myelofibrosis (PMF), post-polycythaemia vera myelofibrosis (PPV-MF), and post-essential thrombocythaemia myelofibrosis (PET-MF) (collectively referred to as ‘MF’)

E.1.1.1

Medical condition in easily understood language

Myelofibrosis: a condition in which the bone marrow is gradually replaced by fibrous, scar-like tissue that prevents the marrow from making normal blood cells.

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10074692
E.1.2	Term	Post essential thrombocythaemia myelofibrosis
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10074691
E.1.2	Term	Post polycythaemia vera myelofibrosis
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10077161
E.1.2	Term	Primary myelofibrosis
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the safety and tolerability of IMG-7289 when administered orally on a daily basis to patients with myelofibrosis. This will be evaluated by clinical assessments of safety parameters i.e. safety laboratory testing, adverse event reporting, physical examination and vital sign assessments.
The second primary objective is to assess the change in spleen volume due to treatment with IMG-7289.
An additional objective for the phase 1/2a portion of this study (which is already complete) was to assess the pharmacokinetics of IMG-7289 (The EU will participate in the phase 2b expansion protocol and this assessment will not be made in patients enrolled here; no further detail provided on PK in this application)

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Willing and able to sign the approved informed consent.
2. Age: 18+ years old at Screening.
3. Diagnosis of either PMF per World Health Organization (WHO) diagnostic criteria for myeloproliferative neoplasms (Section 16.2), PPV-MF per the IWG-MRT (Section 16.3), or PET-MF per the IWG-MRT (Section 16.4) and meet the following additional subtype specific criteria:
a. Classified as high risk (3 prognostic factors) OR intermediate risk-2 (2 prognostic factors). The prognostic factors, defined by the International Working Group (Cervantes, et al., 2009):
i. Age > 65 years;
ii. Presence of constitutional symptoms (weight loss, fever, night sweats);
iii. Marked anaemia (Hgb < 10g/dL)*;
iv. History of leukocytosis [WBC > 25 x109/L (25,000/µL)];
v. Circulating blasts ≥ 1%.
*A haemoglobin value < 10 g/dL must be demonstrated during Screening for patients who are not transfusion dependent. Patients receiving regular transfusions of packed red blood cells will be considered to have haemoglobin < 10 g/dL for the purpose of evaluation of risk factors.
4. Be refractory or resistant to, inadequately controlled by or intolerant of available approved therapy, or in the Investigator’s judgment, are not candidates for available approved therapy (note: approved therapy includes ruxolitinib).
5. Eastern Cooperative Oncology Group (ECOG) performance status score ≤2.
6. Peripheral blast count ≤10% prior to dosing on Day 0.
7. Absolute neutrophil count ≥ 0.5 x 109/L (500/µL) prior to dosing on Day 0
8. Platelet count ≥ 100 x 109/L (100,000/µL) prior to dosing on Day 0.
9. Life expectancy >36 weeks.
10. Have discontinued all previous therapies for MPNs including ruxolitinib, any chemotherapeutic agents, immunosuppressive therapy (e.g., corticosteroids > 10 mg/day with the noted exception: use of corticosteroids for management of gout is allowed; maintenance supplemental corticosteroid therapy such as prednisone ≤ 10 mg/day or corticosteroid equivalent is allowed), immune modulators (e.g., thalidomide), radiotherapy for at least 2 weeks prior, and interferon for 4 weeks prior to study Day 0. Low dose acetylsalicyclic acid is permitted. Palliative radiation treatment to non-index or bone lesions performed < 2 weeks before treatment may be considered with Medical Monitor approval.
11. Amenable to bone marrow evaluation, peripheral blood and urine sampling during the study.
12. Able to swallow capsules.
13. Women of childbearing potential (WOCBP) and fertile men (see Section 6.1) must agree to use an approved method of contraception from Screening until 28 days* after last IMG-7289 dose. Methods of contraception include: estrogen and progestogen combined hormonal contraception which inhibits ovulation; progestogen-only hormonal contraception associated with inhibition of ovulation; intrauterine device (IUD); bilateral tubal occlusion; vasectomized partner in a monogamous sexual relationship (vasectomy or tubal ligation at least six months prior to dosing); and, complete sexual abstinence (defined as refraining from heterosexual intercourse). Patients practicing abstinence must agree to use an approved method of contraception should they become sexually active during the study.
Note: In the UK, males with a pregnant partner must agree to use a condom to avoid exposure to the developing child.
*The risk of embryofetal toxicity is fully mitigated by 28 days which is >10 half-lives of the drug at the doses used in this study.

E.4

Principal exclusion criteria

1. Has undergone major surgery ≤4 weeks prior to starting study drug or has not recovered from side effects of such surgery.
2. Has undergone any surgical procedure within 2 weeks, excluding minor procedures (e.g., skin biopsy or central venous catheter placement/removal) prior to starting study drug.
3. History of splenectomy.
4. History of or scheduled haematopoietic stem-cell transplant within 24 weeks of screening.
5. Unresolved treatment related toxicities from prior therapies (unless resolved to ≤ Grade 1).
6. Current use of a prohibited medication (e.g., romiplostim) or expected to require any of these medications during treatment with the investigational drug.
7. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to IMG-7289 or LSD1 inhibitors (i.e., monoamine oxidase inhibitors; MAOIs) that contraindicates their participation.
8. Current use of monoamine oxidase A and B inhibitors (MAOIs).
9. Uncontrolled active infection.
10. A concurrent second active and non-stable malignancy (patients with a concurrent second active but stable malignancy, such as non-melanoma skin cancers, are eligible).
11. Evidence at the time of Screening of risk of bleeding, including any of the following:
a. Activated partial thromboplastin time (aPTT) ≥ 1.3 x the local upper limit of normal
b. International normalized ratio (INR) ≥ 1.3 x the local upper limit of normal
c. History of severe thrombocytopenia or platelet dysfunction unrelated to a myeloproliferative disorder or its treatment
d. Known bleeding disorder (e.g., dysfibrinogenaemia, factor IX deficiency, haemophilia, Von Willebrand's disease, Disseminated Intravascular Coagulation [DIC], fibrinogen deficiency, or other clotting factor deficiency)
12. Evidence at the time of Screening of significant renal or hepatic insufficiency (unless due to haemolysis, or leukaemic infiltration) as defined by any of the following local lab parameters:
a. Calculated glomerular filtration rate (GFR; using the Cockcroft-Gault equation) <40 mL/min or serum creatinine > 1.5 x the local upper limit of normal
b. Aspartate transaminase (AST) or alanine aminotransferase (ALT) ≥2 x the local upper limit of normal
13. Known human immunodeficiency virus (HIV) infection or known active Hepatitis B or Hepatitis C virus infection (testing will not be conducted as part of Screening procedures).
14. History of any illness/impairment of gastrointestinal (GI) function that might interfere with drug absorption (e.g., chronic diarrhea), confound the study results or pose an additional risk to the patient by participation in the study; patients with gastric bypass surgery.
15. Use of an investigational agent within less than 14 days, or the equivalent of at least 7 half-lives of that agent, whichever is the longer, prior to study Day 0.
16. Pregnant or lactating females; females intending to become pregnant within 6 months; females intending to become pregnant at any time during the study

E.5 End points

E.5.1

Primary end point(s)

Safety and Tolerability:
• The safety and tolerability of IMG-7289 will be assessed by the analysis of adverse events (AEs), as well as changes in physical examinations, vital signs and laboratory values as detailed below.
o Monitoring of Adverse Events (AEs) including determination of dose limiting toxicities (DLTs), serious adverse events (SAEs), and AEs. AEs will be assessed post-first dose until 28 days post-last dose in terms of onset, duration, seriousness, severity, and causality, using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.03. Deaths and other serious adverse events (SAEs) will also be evaluated and will be collected on a separate electronic case report form (eCRF).
o Changes in physical examinations, vital signs and laboratory values will also be evaluated and assessed from Screening/Baseline until EoS/ET. The following laboratory tests will be conducted, with timing dependent on the schedule of assessments:
 Complete blood counts (CBC) and differential
 Coagulation
 Chemistry panel including LFTs (AST, ALT, total bilirubin, gamma glutamyltransferase (GGT), and albumin)
 Urinalysis

Reduction in Spleen Volume:
• Reduction in spleen volume will be assessed based on spleen volume measured by MRI (or CT scan where applicable) from Day 0 and spleen size measured by palpation from Baseline to each visit where the variables are measured.

E.5.1.1

Timepoint(s) of evaluation of this end point

Safety and Tolerability:
• Adverse events will be assessed from Day 0 (post first dose) up to and including the patient's last study visit.
• Changes in physical examinations, vital signs and laboratory values will be assessed from Screening up to and including the patient's last study visit (End of Study or Early Termination)

Reduction in spleen volume:
• Reduction in spleen volume will be assessed from Day 0 to each visit where the variables are measured.

E.5.2

Secondary end point(s)

Not Applicable.

E.5.2.1

Timepoint(s) of evaluation of this end point

Not Applicable

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

United States

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The End-of-Trial date is considered to be the date of Database Lock. The justification is that the trial only ends when all queries are answered and the database is cleaned. Until that point, sites and/or patients may be called upon for follow up information or clarification of data.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1