Clinical Trials Register

Summary
EudraCT Number:	2020-002460-31
Sponsor's Protocol Code Number:	BTI-202
National Competent Authority:	Romania - National Agency for Medicines and Medical Devices
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-06-23
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

Romania - National Agency for Medicines and Medical Devices

A.2

EudraCT number

2020-002460-31

A.3

Full title of the trial

A PHASE 2 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PROOF-OF-CONCEPT STUDY TO EVALUATE THE EFFICACY AND SAFETY OF RECOMBINANT HUMAN PLASMA GELSOLIN (RHU-PGSN) ADDED TO STANDARD OF CARE FOR TREATMENT OF SUBJECTS WITH SEVERE COVID-19 PNEUMONIA

Studiu de fază 2, randomizat, dublu-orb, controlat cu placebo, de validare a conceptului (Proof-of-Concept) pentru evaluarea eficacităţii şi siguranţei gelsolinei plasmatice umane recombinante (rhu-pGSN) adăugate la regimul standard de ingrijire pentru tratamentul subiecţilor cu pneumonie severă cu COVID-19

A.3.1

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

A.4.1

Sponsor's protocol code number

BTI-202

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	BioAegis 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	BioAegis 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	BioAegis Therapeutics, Inc.
B.5.2	Functional name of contact point	Susan L. Levinson-Chief Executive O
B.5.3	Address:
B.5.3.1	Street Address	6 East Cove Lane
B.5.3.2	Town/ city	Morristown
B.5.3.3	Post code	07960
B.5.3.4	Country	United States
B.5.4	Telephone number	001973-539-4552
B.5.6	E-mail	slevinson@bioaegistx.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	rhu-pGSN
D.3.2	Product code	recombinant human plasma Gelsolin
D.3.4	Pharmaceutical form	Lyophilisate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous bolus use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	recombinant human plasma Gelsolin
D.3.9.2	Current sponsor code	B2988
D.3.9.3	Other descriptive name	Human plasma gelsolin, recombinant
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	40
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 injection/infusion in pre-filled syringe
D.8.4	Route of administration of the placebo	Intravenous bolus use (Noncurrent)

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

severe COVID-19 pneumonia

E.1.1.1

Medical condition in easily understood language

Severe pneumonia due to COVID-19

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	23.0
E.1.2	Level	LLT
E.1.2	Classification code	10084401
E.1.2	Term	COVID-19 respiratory infection
E.1.2	System Organ Class	100000004862

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

-To assess the efficacy (survival without organ failure on Day 14) of intravenous (IV) rhu-pGSN plus standard of care (SOC) vs placebo plus SOC (hereafter referred to as rhu-pGSN vs placebo) administered to hospitalized subjects with a primary diagnosis of Coronavirus 2019 (COVID-19) pneumonia and a severity score of 4, 5, or 6 on the World Health Organization (WHO) 9-point severity scale
-To evaluate the safety (incidence of serious adverse events [SAEs]) of IV rhu-pGSN administered to hospitalized subjects with a primary diagnosis of COVID-19 pneumonia and a severity score of 4, 5, or 6 on the WHO 9-point severity scale

E.2.2

Secondary objectives of the trial

- To further assess the efficacy of IV administered rhu-pGSN
- To measure changes in the WHO 9-point severity scale for SOC ± rhu-pGSN
- To evaluate the effect of administered rhu-pGSN on survival rates
- To assess the relationship of pGSN levels (and other biomarkers) at baseline with clinical outcomes
- [OPTIONAL] To follow the pharmacokinetics (PK) of administered rhu-pGSN

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Hospitalized with laboratory-confirmed (RT-PCR+) or highly suspected (compatible with at least bilobar lung involvement without another plausible diagnosis) COVID-19
- Age ≥18 years
- Weight ≤100 kg
- Within 24 hours of reaching a WHO severity score of 4-6 either:
- At admission
- While already hospitalized.
Informed consent obtained from subject/next of kin/legal proxy
Primary admitting diagnosis of pneumonia supported by a compatible clinical presentation with a documented infiltrate consistent with pneumonia on CXR or CT, as assessed by the admitting emergency department (ED), clinic, or ward physician or equivalent caregiver
Recommended (not mandatory) guidance/discretionary criteria defining patients with pneumonia satisfying all 4 categories below:
- At least 2 symptoms: difficulty breathing, cough, production of purulent sputum, or chest pain
- At least 2 vital sign abnormalities: fever, tachycardia, or tachypnea (thresholds -- fever: oral or core temperature >100.4°F [38°C]; heart rate >100 beats/min; respiratory rate >24/min)
- At least one finding of other clinical signs and laboratory abnormalities: hypoxemia (O2 saturation <90%), clinical evidence of pulmonary consolidation, or leukocytosis ≥1.5x104 or leukopenia <4x103
- Chest imaging, or CT chest showing at least bilobar pulmonary infiltrates
Principal Investigator (PI) to note radiologic findings in the electronic case report form (eCRF)
Radiology report to be placed in the eCRF
A copy of the radiograph attached to be saved for review
A hyperinflammatory status (defined by increased ferritin ≥500 µg/L, D-dimer ≥1000 ng/mL, or CRP ≥75 mg/L)
During the course of the study starting at screening and for at least 6 months after their final study treatment:
- Female subjects of childbearing potential must agree to use 2 medically accepted birth control methods
- Male subjects with a partner who might become pregnant must agree to use reliable forms of contraception (i.e., vasectomy, abstinence), or an acceptable method of birth control must be used by the partner
- All subjects must agree not to donate sperm or eggs (ovocytes)

E.4

Principal exclusion criteria

- A negative RT-PCR test for COVID-19 during the evaluation of the present illness
- Extracorporeal membrane oxygenation (ECMO)
- Pregnant or lactating women
- Active underlying cancer treated with systemic chemotherapy or radiation therapy during the last 30 days
- Transplantation of hematopoietic or solid organs
- Chronic mechanical ventilation or dialysis
- Otherwise unsuitable for study participation because of chronic, severe, end-stage, and life-limiting underlying disease unrelated to COVID-19 likely to interfere with management and assessment of acute pneumonia, only comfort or limited (non-aggressive) care is to be given, or life expectancy <6 months unrelated to acute COVID infection in the opinion of the Investigator

E.5 End points

E.5.1

Primary end point(s)

Safety and tolerability
- Incidence of SAEs in rhu-pGSN vs placebo group
Efficacy
-Proportion of subjects alive not on vasopressors, mechanical ventilator, and dialysis on Day 14

E.5.1.1

Timepoint(s) of evaluation of this end point

Safety and tolerability- 90 days
Efficacy -Day 14 after start of study treatment

E.5.2

Secondary end point(s)

Safety and tolerability
- Incidence, causality, and severity of AEs (graded according to the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version 5.0) in rhu-pGSN vs placebo groups
- Frequencies of new or worsening clinically significant laboratory abnormalities in rhu-pGSN vs placebo groups
- Mortality rate irrespective of cause at Days 28 and 90
• Efficacy
- Daily change in 9-point WHO severity score through at least Day 14
- All-cause mortality at Days 28 and 90; time to death (Kaplan-Meier survival analysis)
- Proportion of subjects alive on Days 7, 14, 28, 60, and 90 without:
Ongoing use of vasopressors
Ongoing intubation/mechanical ventilation
Ongoing residence in an ICU
New ongoing need for dialysis/renal replacement therapy (RRT)
- Proportion of subjects discharged to home or immediate prior residence by Day 28
- Days on the ventilator
- Length of stay (LOS) in hospital and in ICU (days)
- Re-admission to an acute-care hospital up to Day 90
• PK (Optional)
- PK for rhu-pGSN including maximum concentration (Cmax), time to maximum concentration (Tmax), terminal half-life (T1/2), area under the curve from time zero to 8 hours (AUC0-8), area under the curve from time 0 to infinity (AUCinf) for Dose #1 within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), and 12 (±30 min) hours after end of administration (but prior to Dose #2); for Dose #3 within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), 12 (±30 min) and 24 (±30 min) hours after the end of administration (participants refusing these blood samplings can enter and remain in the trial).
• Immunogenicity
- Presence of anti pGSN antibodies on Days 1 (predose), 28, and 90

E.5.2.1

Timepoint(s) of evaluation of this end point

Days 7, 28, 60 (optional), and 90

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

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.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the 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

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

LPLV

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

patient in Covid quarantine or unable to give consent due to heath status

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-10-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-10-06

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-11-22

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