Clinical Trials Register

Summary
EudraCT Number:	2020-001027-13
Sponsor's Protocol Code Number:	SELK2-00006
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:	2020-05-06
Trial 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

2020-001027-13

A.3

Full title of the trial

A Two Part, Randomised, Double-blind, Placebo-controlled, Phase 2 Parallel Group Study to Evaluate the Safety and Efficacy of Intravenously-Administered SelK2 on Airway Responses Following Allergen Challenge in Subjects with Asthma (Part 1) and to Evaluate the Safety and Efficacy of Intravenously-Administered SelK2 in Subjects with Chronic Obstructive Pulmonary Disease (Part 2)

A.3.1

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

A Study of SelK2 in Subjects with Asthma (Part 1) and COPD (Part 2)

A.3.2

Name or abbreviated title of the trial where available

A Study of SelK2 in Subjects with Asthma (Part 1) and COPD (Part 2)

A.4.1

Sponsor's protocol code number

SELK2-00006

A.5.4

Other Identifiers

Name:

MEU number

Number:

MEU 19/392

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	Tetherex Pharmaceuticals Corporation
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	Tetherex Pharmaceuticals Corporation
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	Tetherex Pharmaceuticals Corporation
B.5.2	Functional name of contact point	Jonathan Stocker
B.5.3	Address:
B.5.3.1	Street Address	840 Research Parkway, Suite 516
B.5.3.2	Town/ city	Oklahoma City
B.5.3.3	Post code	OK 73104
B.5.3.4	Country	United States
B.5.4	Telephone number	919-819-2112
B.5.5	Fax number	405-319-8197
B.5.6	E-mail	jstocker@tetherex.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	SelK2
D.3.2	Product code	SelK2
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Humanized anti-PSGL-1 monoclonal antibody
D.3.9.2	Current sponsor code	SelK2
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Part 1: Asthma
Part 2: Chronic Obstructive Pulmonary Disease (COPD)

E.1.1.1

Medical condition in easily understood language

Part 1: Asthma
Part 2: Chronic Obstructive Pulmonary Disease (COPD)

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	20.0
E.1.2	Level	PT
E.1.2	Classification code	10003553
E.1.2	Term	Asthma
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

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	10009033
E.1.2	Term	Chronic obstructive pulmonary disease
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

Part 1
Evaluate SelK2 for its ability to reduce the late asthmatic response (LAR) in terms of maximum percentage fall in FEV1 (forced expiratory volume in one second) after inhaled allergen challenge (breathing in a fine mist of the allergen that the participant is sensitive to).

Part 2
Evaluate the effect of SelK2 on neutrophil percentage in sputum (phelgm).

E.2.2

Secondary objectives of the trial

Part 1 - Secondary
•Evaluate SelK2 for its ability to reduce the LAR in terms of area under the curve (AUC) for the FEV1 after inhaled allergen challenge.
•Evaluate the effect of SelK2 on the eosinophil percentage in sputum.
•Evaluate the effect of SelK2 on the early asthmatic response (EAR) after inhaled allergen challenge.
•Evaluate the effect of SelK2 on the overall asthmatic response from 0-8 hours after inhaled allergen challenge.
•Evaluate the effect of SelK2 on pre-challenge FEV1.
•Evaluate the overall safety and tolerability of 2 doses of intravenous SelK2.
•Further describe the Pharmacokinetics (PK - study drug levels and the time it takes for your body to break down the study drug) and Pharmacodynamics (PD; inhibition of PSGL-1/P-selectin binding) of SelK2 after giving 2 doses.
•Evaluate the immunogenicity (Human Anti-Human Antibody [HAHA] response) following 2 doses of SelK2. To see if the body is making antibodies against the study medication.

Part 1 - Exploratory
•Evaluat

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Part 1:
1.Subject’s written informed consent obtained prior to any study-related procedure.
2.Male or female, 18 to 65 years of age, inclusive, at the time of informed consent.
3.Female subjects must be either of non-childbearing potential or if of childbearing potential use a highly effective birth control method (See Section 9.4.2).
4.Female subjects must agree not to donate ova/oocytes during the study and for 6 months after the last dose of investigational Medicinal Product (IMP).
5.Male subjects (with partners of child-bearing potential) must use highly effective contraception (See Section 9.4.1).
6.Male subjects must agree not to donate semen during the study and for 3 months after the last dose of IMP.
7.Body Mass Index (BMI) ≥ 18.0 and ≤ 35.0 kg/m2 at Screening.
8.Documented physician-diagnosed asthma for ≥ 4 months prior to screening.
9.Pre-bronchodilator FEV1 ≥ 70% predicted at screening.
10.Documented allergy to at least one common allergen as confirmed by the skin prick test, with wheal diameter ≥3mm greater than the negative control. Historical data up to one year prior to screening can be used.
11.Dual responder to inhaled bronchial allergen challenges as manifested by positive allergen-induced early (EAR) and late airway bronchoconstriction (LAR) at screening, defined as follows:
•EAR is defined as a fall in FEV1 of at least 20% from pre-challenge post diluent baseline values during the 30 minutes after inhaled bronchial allergen challenge;
•LAR is defined by a fall from post diluent value of FEV1 of at least 15% on at least 3 occasions, 2 of which must be consecutive, between 3 to 8 hours after inhaled allergen challenge.
12.Sputum producer stratum only (minimum of 20 of the 36 planned subjects): Subject is able to tolerate sputum induction and produce adequate sputum after bronchial allergen challenge during the screening period (either at the 8˗hour or 24˗hour post allergen time points).
13.No clinically significant abnormalities as determined by the investigator in the results of laboratory evaluations at screening.
14.Clinical findings from the 12-lead ECG or vital signs that are deemed medically acceptable as determined by the investigator at Screening and prior to randomisation.
15.Has a negative result in the blood test for tuberculosis (TB) at screening.
16.Understands the study procedures in the informed consent form (ICF) and is willing and able to comply with the protocol-defined study procedures, restrictions and expectations.

Part 2:
1.Subject’s written informed consent obtained prior to any study-related procedure.
2.Male or female, 40 to 75 years of age, inclusive, at the time of informed consent.
3.Confirmed diagnosis by a physician of COPD with symptoms compatible with COPD for at least 1 year prior to screening.
4.Female subjects must be either of non-childbearing potential or if of childbearing potential use a highly effective birth control method (See Section 9.4.2).
5.Female subjects must agree not to donate ova/oocytes during the study and for 6 months after the last dose of IMP.
6.Male subjects (with partners of child-bearing potential) must use highly effective contraception (See Section 9.4.1).
7.Male subjects must agree not to donate semen during the study and for 3 months after the last dose of IMP.
8.BMI ≥ 18.0 and ≤ 35.0 kg/m2 at screening.
9.Able to tolerate sputum induction and produce an adequate sputum sample with a neutrophil differential count > 55% at screening.
10.Post-bronchodilator FEV1 ≥ 30% and ≤ 80% of the predicted normal, and post-bronchodilator FEV1/FVC < 0.7 at the time of Screening.
11.Current or former tobacco smoker who has a smoking history of at least 10 pack years (Ten pack- years are defined as 20 cigarettes a day for 10 years, or 10 cigarettes a day for 20 years).
12.No clinically significant abnormalities as determined by the investigator in the results of laboratory evaluations at screening.
13.Clinical findings from the 12-lead ECG or vital signs that are deemed medically acceptable as determined by the investigator at screening and prior to randomisation.
14.Has a negative result in the blood test for tuberculosis (TB) at screening
15.Understands the study procedures in the ICF and is willing and able to comply with the protocol-defined study procedures, restrictions and expectations.

E.4

Principal exclusion criteria

Part 1.
-Lung disease other than stable, mild asthma; worsening of asthma that requires a change in asthma therapy in the past 4 weeks or is deemed clinically significant (CS).
-Has a history of life-threatening asthma, defined as an asthma episode that required intubation and/or was associated with hypercapnea, respiratory arrest and/or hypoxic seizures.
-Has been hospitalised or has attended the emergency room for asthma in the last 12 months.
-Positive urine cotinine test result at screening or prior to randomisation.
-Uses or has used tobacco or nicotine-containing products within 12 months prior to screening, or prior to randomisation.
-Smoking history of a cumulative tobacco exposure of > 5 pack years.

Part 2.
-COPD exacerbation requiring oral steroids &/or antibiotics, within the last 8 weeks.
-A positive sputum culture at Screening indicating ongoing infection.
-Other respiratory disorders other than COPD.
-A history of life-threatening COPD including ICU admission &/or requiring intubation within the last 5 years.
-A history of > 1 hospitalisation for COPD in the previous 1 year.
-Evidence of cor pulmonale or CS pulmonary hypertension.
-Current clinically significant sleep apnoea requiring non-invasive ventilation or supplemental oxygen during sleep.
-Previous lung resection, lung reduction surgery or lung transplantation.
-Requires supplemental oxygen, even on an occasional basis.
-Active participation in a pulmonary rehabilitation program.
-Inability to perform impulse oscillometry, whole body plethysmography or technically acceptable spirometry.

Parts 1 & 2
-History of CS hypotensive episodes or symptoms of fainting, dizziness, or light-headedness.
-History of lymphoma, leukemia, or other types of malignancy except for completely resected squamous/basal cell cancer.
-Any infection requiring hospitalisation or intravenous antibiotics within 6 months.
-A diagnosed current or recent (within 8 weeks) bacterial, protozoal, viral, parasitic infection; is suspected of or is at high risk of having a parasitic infection or has a history of > 1 episode of herpes zoster infection.
-Evidence of current or previous CS disease with the exception of stable, mild asthma (Part 1) or stable COPD (Part 2).
-Has an eGFR of <60 mL/min/1.73m2 at screening, based on MDRD equation.
-Has had major surgery in the last 2 months or is anticipating surgery during the study or follow-up period
-History of any drug or alcohol abuse in the past 2 years.
-Positive breath alcohol results at screening, or prior to randomisation.
-Positive urine drugs of abuse test result (unless this can be explained by the subject’s current medications) at screening or prior to randomisation.
-History of hypersensitivity to drugs, latex allergy, band aids, adhesive dressing, or medical tape, with a CS reaction.
-History of serious adverse reaction, severe hypersensitivity or allergy to any drug or in any other circumstance.
-Females with a positive pregnancy test at screening, or prior to randomisation, or who are lactating.
-Has received treatment with a live vaccine within 3 months prior to screening, or prior to randomisation.
-Positive HBsAg, HCV Ab or HIV results. Subjects who are HBs antibody positive or HB core antibody positive are not excluded provided the HBsAg result is negative. Subjects who are HCV Ab positive are not excluded if a subsequent HCV RNA test is negative.
-A history of TB (latent or active) or systemic fungal diseases.
-Receiving any of the prohibited concomitant medications.
-Exposure to biologic therapies within the last 6 months.
-Has dietary restrictions incompatible with the diet that can be provided by the study site.
-Donated blood/blood products or had substantial loss of blood (more than 500 mL) within the last 3 months, or intention to donate blood/blood products during the study.
-Previously received SelK2.
-Known sensitivity to the study drug or any of the excipients of the formulation, or history of CS sensitivity to any agent that, in the opinion of the investigator, would make participation in the study inadvisable.
-Received an investigational drug within 8 weeks (or 6 months for biologics) or within 5 half-lives (if known) whichever is longer, prior to screening, or prior to randomisation.
-Inability to comply with study procedures, required restrictions or any other reason that the Investigator considers makes the subject unsuitable to participate.
-Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator.
-Employee of the Investigator or study centre with direct involvement in the proposed study or other studies under the direction of that Investigator or study centre, as well as family members of the employees or the Investigator.

E.5 End points

E.5.1

Primary end point(s)

Part 1:
•Maximum percentage fall in FEV1 from pre-challenge between 3 and 8 hours (LAR) after administration of allergen inhalation challenge.

Part 2:
•Change from baseline in percentage of neutrophils in sputum on Day 22.

E.5.1.1

Timepoint(s) of evaluation of this end point

Part 1:
•FEV1 measured at Day 36 from pre-allergen challenge and the period beginning 3 hours and ending 8 hours after the allergen challenge.

Part 2:
Days 22

E.5.2

Secondary end point(s)

Part 1 Secondary:
1. AUC for the percent fall in FEV1 from pre-challenge between 3 and 8 hours (LAR) after the administration of allergen inhalation challenge.
2. Change from baseline and change during challenge in percentage of eosinophils in sputum measured at 8 and 24 hours post allergen challenge.
3. Maximum percentage fall in FEV1 and AUC for the percent fall in FEV1 from pre-challenge between 0 and 2 hours after the administration of allergen inhalation challenge (EAR).
4. Maximum percentage fall in FEV1 and AUC for the percent fall in FEV1 between 0 and 8 hours (entire asthmatic response) after the administration of allergen.
5. Change from baseline in pre-challenge FEV1.

Part 1 Exploratory:
6. Change from baseline and change during challenge in absolute and percentage cell counts for immune cells in induced sputum samples and blood (except for eosinophils in sputum which is a secondary endpoint).
7. Change from baseline and change during challenge in fractional exhaled nitric oxide.
8. Change from baseline and change during challenge in biomarkers of inflammation in both sputum and blood.
9. Change in subject reported outcome as captured by Asthma Control Questionnaire 5-Question Version (ACQ-5) Score.

Part 2 Secondary:
1. Change from baseline in percentage of neutrophils on Day 4, 8, 15, and 29.
2. Change from baseline in absolute and percentage cell counts for immune cells in induced sputum samples and blood (except for neutrophils in sputum which is the primary endpoint) on Days 4, 8, 15, 22, 29.
3. Change from baseline in FEV1 and post-bronchodilator FEV1 on Days 4, 8, 15, 22, and 29.
4. Change from baseline in pre- and post-bronchodilator impulse oscillometry (IOS) on Days 4, 8, 15, 22, and 29.
5. Change from baseline in pre- and post-bronchodilator Whole body plethysmography on Days 4, 8, 15, 22, and 29.
6. Change from baseline for subject reported outcomes: COPD Assessment Test (CAT) scores and Breathlessness Cough and Sputum Scale (BCSS) scores on Days 4, 8, 15, 22, and 29.

Part 2 Exploratory:
7. Change from baseline in biomarkers of inflammation in both sputum and blood.

Part 1 and Part 2:
Safety:
Safety evaluations will include medical history, physical examinations, evaluation of AEs (including a general query such as “How do you feel?”), BMI, 12-lead ECGs, vital signs (including tympanic temperature, respiratory rate, and supine blood pressure and pulse), spirometry, clinical laboratory evaluations; clinical chemistry (fasted at least 8 hours; water permitted), coagulation parameters (prothrombin time, activated partial thromboplastin time, international normalised ratio, D-dimer), haematology, urinalysis, and pregnancy test (all female subjects).

PK, PD and Human Anti-Human Antibodies (HAHA) Analyses:
Assessment of PK (sera concentrations of SelK2), PD (inhibition of PSGL-1/P-selectin binding), and immunogenicity (HAHA) for all subjects dosed with SelK2.

E.5.2.1

Timepoint(s) of evaluation of this end point

Part 1
1. Pre-BAC & between 3-8 hrs post-BAC (Day 36)
2. Pre-BAC, 8, 24 hrs post-BAC (Day 36)
3. Pre-BAC & between 0-2 hrs post-BAC (Day 36)
4. Pre-BAC & between 0-8 hrs post-BAC (Day 36)
5. Pre-BAC
6, 8. Screen, Day 29, 8-24 hrs post each BAC
7. Screen, Days 1, 8, 15, 22, 29, 43, 57, pre-BAC, 8-24 hrs post each BAC
9. Screen, Days 1, 8, 22, 36, 57

Part 2
1. Screen, Days 4, 8, 15, 29
2, 3, 4, 5, 6. Screen, Days 4, 8, 15, 22, 29
7. Screen, Days 4, 8, 15, 22, 29, 43

Safety: All relevant time-points as per protocol
PK/PD (Part 1): Day 1 (pre, 15, 30 mins, 1 hr), 2, 8, 15, 22 (pre, 15, 30 mins, 1hr), 23, 29, 36, 43, 50, 57
PK/PD (Part 2): Day 1 (pre, 1 hr), 4, 8, 15, 22, 29, 43
HAHA (Part 1): Day 1, 15, 22, 29, 43, 57
HAHA (Part2): Day 1, 22, 43

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

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

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

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

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Placebo controlled

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.8.2.4

Number of treatment arms in the trial

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

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 the study is defined as the last subject last visit (or last subject contact if final follow-up contact is by other means than “in person”), whether that visit is scheduled or not.

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