Clinical Trials Register

Summary
EudraCT Number:	2019-004998-34
Sponsor's Protocol Code Number:	B-2660-203
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2020-02-04
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

2019-004998-34

A.3

Full title of the trial

A Phase 2a, Double-Blind, Placebo-Controlled Study to Evaluate Pharmacodynamics, Pharmacokinetics, and Safety of BLD-2660 Administered Orally in Subjects with Idiopathic Pulmonary Fibrosis

A.3.1

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

A clinical study to investigate the safety and effects of a new drug called BLD-2660 in patients with Idiopathic Pulmonary Fibrosis

A.3.2

Name or abbreviated title of the trial where available

B-2660-203

A.4.1

Sponsor's protocol code number

B-2660-203

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	Blade Therapeutics, 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	Blade Therapeutics, 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	Blade Therapeutics, Inc.
B.5.2	Functional name of contact point	Daven Mody
B.5.3	Address:
B.5.3.1	Street Address	442 Littlefield Avenue
B.5.3.2	Town/ city	South San Francisco, CA
B.5.3.3	Post code	94080
B.5.3.4	Country	United States
B.5.4	Telephone number	(650) 797-0282
B.5.5	Fax number	(650) 745-0887
B.5.6	E-mail	dmody@blademed.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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	BLD-2660
D.3.2	Product code	BLD-2660
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	None
D.3.9.2	Current sponsor code	BLD-2660
D.3.9.3	Other descriptive name	BLD-2660
D.3.9.4	EV Substance Code	AS1
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	150
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
D.8.3	Pharmaceutical form of the placebo	Capsule, hard
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Idiopathic Pulmonary Fibrosis

E.1.1.1

Medical condition in easily understood language

A type of lung disease that results in scarring (fibrosis) of the lungs for unknown reason. Overtime, it becomes hard to take in a deep breath and the lungs cannot take enough oxygen.

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10021240
E.1.2	Term	Idiopathic pulmonary fibrosis
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

PRIMARY OBJECTIVE
• To establish the study drug interaction with its intended target in cells isolated from Bronchoalveolar lavage
• To evaluate biochemical and physiologic effects of the study drug (Pharmacodynamics) and to evaluate the indicators or markers in the blood (Biomarkers) and Bronchoalveolar lavage fluid.

E.2.2

Secondary objectives of the trial

• To study how the BLD-2660 enters, moves through and exits the body (Pharmacokinetics) in IPF subjects.
• To establish safety and tolerability of BLD-2660 in subjects with IPF.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

To be eligible for inclusion into this study, each subject must fulfil the following inclusion criteria within 20 days prior to Randomisation on Day 1.

Age and Gender
1. Male subjects 45 years of age and over, or female subjects 50 years of age and over, at the time of signing the informed consent.

Diagnosis and disease characteristics
2. Subjects with diagnosis of IPF as defined by the American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of Idiopathic Interstitial Pneumonia (Raghu, 2018).
3. FVC >45% predicted and diffusing capacity of the lung for carbon monoxide (DLCO) >30% predicted.
4. Alanine aminotransferase (ALT) within normal limits (WNL).
5. Aspartate aminotransferase (AST) and alkaline phosphatase (ALP) ≤1.2 × upper limit of normal (ULN).
6. Total bilirubin ≤ULN (isolated bilirubinemia ≤2× ULN is acceptable if direct bilirubin to total bilirubin ratio <0.35).
7. Body mass index (BMI) up to 35 kg/m2 inclusive.

Reproductive Considerations
Contraception use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
8. All subjects (male or female) who are of childbearing potential must agree to use highly effective contraception during the study, including:
• intrauterine device (IUD);
• bilateral tubal occlusion;
• vasectomised partner a;
• sexual abstinence b.
Notes: a Vasectomised partner is a highly effective birth control method provided that the partner is the sole sexual partner of the women of childbearing potential (WOCBP) trial participant and that the vasectomised partner has received medical assessment of the surgical success.
b Sexual abstinence is defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject.
Hormonal contraceptives (HC) are restricted during the study.

9. Male subjects and female partners of male subjects must continue to use highly effective contraception, as listed in Inclusion criterion 8, for 90 days after the last dose of study drug. Male subjects must agree not to donate sperm for 90 days after last dose of study drug.
10. Female subjects and male partners of female subjects must continue to use highly effective contraception, as listed in Inclusion criterion 8, for 60 days after the last dose of study drug. Female subjects should not donate oocytes during this time.
11. Female subjects of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day (-1). WOCBP must agree to undergo pregnancy testing at regular intervals throughout the study.
12. Female subjects not of childbearing potential as defined by being postmenopausal (with cessation of regular menstrual periods for at least 1 year), confirmed by follicle stimulating hormone (FSH) level, or be surgically sterile.

Informed Consent
13. Subjects must provide signed informed consent prior to study entry and have the ability and willingness to attend and comply with the necessary visits at the study site.

E.4

Principal exclusion criteria

To be eligible for inclusion into this study, each subject must violate none of the following exclusion criteria within 20 days prior to Randomisation on Day 1:

Medical Conditions
1. Recent (less than 6 weeks) significant wound (in the opinion of the Investigator), or presence of an ongoing non-healing skin wound or ulcer.
2. Presence of any underlying physical or psychological medical condition that, in the opinion of the Investigator, would make it unlikely that the subject will complete the study per protocol.
3. Active infection (diagnosed or suspected) or history of recurrent infections, including but is not limited to, bronchitis, pneumonia, sinusitis, urinary tract infection, cellulitis or chronic ongoing infectious disease within 4 weeks prior to first dose of study drug.
Note: Rescreening will be permitted after 28 days if an infection leads to screening failure.
4. Active malignancy and/or history of malignancy in the past 5 years, except for non-melanoma skin cancer, carcinoma in situ of the breast that has been successfully treated, carcinoma in situ of the cervix that has been successfully treated, early stage, untreated prostate cancer, or prostate cancer with completion of treatment >2 years prior to Screening.
5. Extensive chronic obstructive pulmonary disease (where extent of emphysema >extent of fibrosis on computerised tomography (CT) scan or FEV1: FVC ratio <0.65).
6. Other explanation for lung fibrosis, including but not limited to radiation, sarcoidosis, bronchiolitis obliterans organizing pneumonia, collagen vascular disease, hypersensitivity pneumonitis, etc.
7. IPF exacerbation within last 60 days.
8. A history or current evidence of any medical condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subjects’ participation for the full duration of the study, or is not in the best interest of the subjects to participate, in the opinion of the Investigator.

Diagnostic Assessments
9. Positivity for Human Immunodeficiency Virus (HIV) antibody (HIV-1 and/or HIV-2) and/or HIV-1 p24 antigen.
10. Positivity for Hepatitis C virus antibody (HCV Ab or anti-HCV) and/or Hepatitis B surface antigen (HBsAg).
11. Absolute neutrophil count <1700/μL.
12. Significant hypoxia, requiring >2 L/min oxygen to maintain a resting oxygen saturation >89%.
13. Poor exercise tolerance.
14. Serum troponin I level >ULN.

Prior/Concomitant Therapy
15. Use of anticoagulants that prolong Prothrombin time (PT)/ International normalised ratio (INR).
16. Use of anticoagulants within 2 days of Day (-1) (bronchoscopy)
Note: The subjects who cannot discontinue the anticoagulants within 2 days of Day (-1) bronchoscopy will be excluded.
17. Treatment with any anti-fibrotic therapy (pirfenidone or nintedanib) within 30 days of Screening.
18. Immunosuppressive therapy within 3 months prior to first dose of study drug unless for non-IPF indication).
19. Use of oral steroids >10 mg/day (or prednisolone equivalent).
Note: If the subject is on steroid dose equivalent to 10 mg/day prednisone or more, the Investigator may decide if the tapering down to the dose of 10 mg/day prednisone is possible and safe.
20. Start of new biologic or change in biologic dose within 24 weeks prior to Day 1.
21. Cyclophosphamide within 6 months prior to the first dose of study drug (unless for other indication).

Prior/Concurrent Clinical Study Experience
22. Administration of another investigational product, investigational device, or approved therapy for investigational use within 30 days prior to the first study drug administration, or five half-lives, whichever is longer.

Other Exclusions
23. Blood donation or significant blood loss within 60 days prior to the first study drug administration.
24. Plasma donation within 7 days prior to the first study drug administration.
25. Females who are pregnant or breastfeeding.
26. History or presence of alcohol or drug abuse (including recreational marijuana use) within the 2 year prior to the first study drug administration, and unwillingness to be totally abstinent during the dosing period.
27. Active smoker, smoking history or vaping within 4 weeks prior to the first dose of study drug. Subjects only using Nicotine replacement therapy (NRT) may be allowed per discretion of the Investigator.
28. Subjects with an allergy to BLD-2660 or inactive components of BLD-2660.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoints of the study are:
• Change from baseline in calpain substrates, (i.e., ILK, spectrin, ezrin and/or S100A9) in BAL cells;
• Change from baseline in downstream PD biomarkers (e.g. PAI-1, IL-6, and/or CCL18) in BAL fluid;
• Change from baseline in blood biomarkers that correlate with collagen formation and degradation including Pro-C3, C1M and C3M.

E.5.1.1

Timepoint(s) of evaluation of this end point

• Change from baseline in calpain substrates, (i.e., ILK, spectrin, ezrin
and/or S100A9) in BAL cells - Evaluated on Day (-1) and Day 27
• Change from baseline in downstream PD biomarkers (e.g. PAI-1, IL-6,
and/or CCL18) in BAL fluid -
Evaluated on Day (-1) and Day 27
• Change from baseline in blood biomarkers that correlate with collagen
formation and degradation including Pro-C3, C1M and C3M - Evaluated
on Day (-1), 27 and 42

E.5.2

Secondary end point(s)

Pharmacokinetic Endpoints:
• PK parameters to be estimated on Days 1 and 28 by noncompartmental analysis (NCA) are: maximum plasma concentration
(Cmax), time to Cmax (Tmax), and area under the curve to the final concentration ≥ Lower Limit of Quantification [LLOQ] (AUC0-t) or to the end of the 12-hour dosing interval (AUC0-12). Additional analyses may be performed as deemed necessary upon review of the data;

Safety Endpoints:
• Incidence, nature, and severity of adverse events (AEs) and serious adverse events (SAEs);
• Changes from baseline in electrocardiogram (ECG), vital signs, physical examinations and the following clinical laboratory values: haematology, clinical chemistry, coagulation and urinalysis;
• Proportion of subjects with troponin elevations leading to discontinuation of study drug;
• Proportion of subjects with troponin elevations that persist on retesting as >first elevated troponin value while still on study drug.

E.5.2.1

Timepoint(s) of evaluation of this end point

Pharmacokinetic Endpoints evaluated on Days 1 and 28
Safety Endpoints evaluated during each study visit

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

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

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

Safety, PK, PD and Target Engagement Study with dose de-escalating design

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

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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

Yes

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

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

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

LVLS

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