UMIN-ICDS Clinical Trial

Public title

A Phase 3, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of two dose levels of BCX7353 as an oral treatment for the prevention of attacks in subjects with hereditary angioedema

Acronym

Evaluate study between two doses levels of BCX7353 and placebo for prevention of attacks in subjects with hereditary angioedema

Scientific Title

A Phase 3, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of two dose levels of BCX7353 as an oral treatment for the prevention of attacks in subjects with hereditary angioedema

Scientific Title:Acronym

Evaluate study between two doses levels of BCX7353 and placebo for prevention of attacks in subjects with hereditary angioedema

Region

Japan

Condition

Hereditary angioedema

Classification by specialty

Medicine in general	Gastroenterology	Clinical immunology
Dermatology	Oto-rhino-laryngology	Emergency medicine

Classification by malignancy

Others

Genomic information

YES

Narrative objectives1

1.Part 1: To determine the efficacy of BCX7353 110 and 150 mg administered once daily (QD) for 24 weeks compared to placebo in the prevention of angioedema events in subjects with hereditary angioedema (HAE)
2. Part 2: To evaluate the long-term safety and tolerability of BCX7353 110 and 150 mg in subjects with HAE
3.Part 3: To evaluate the long-term safety and tolerability of BCX7353 administered QD over a
52- to up to 104-week administration period in subjects with HAE

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Pragmatic

Developmental phase

Phase III

Primary outcomes

The rate of expert-confirmed angioedema events during dosing in the entire 24 week treatment period (Days 1 to 168)

Key secondary outcomes

-Change from baseline in Angioedema Quality of Life questionnaire (AE QoL) at Week 24 (total score)
-Number and proportion of days with angioedema symptoms through 24 weeks
-Rate of expert-confirmed angioedema events during dosing in the effective treatment period (beginning on Day 8 through 24 weeks)

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Double blind -all involved are blinded

Control

Placebo

Stratification

YES

Dynamic allocation

YES

Institution consideration

Institution is not considered as adjustment factor.

Blocking

YES

Concealment

Central registration

No. of arms

3

Purpose of intervention

Prevention

Type of intervention

Medicine

Interventions/Control_1

Drug:BCX7353 capsules, to be administered orally
-Treatment Group 1 (110 mg QD) Parts 1 and 2: two 55 mg capsules of BCX7353
-Part1:BCX7353 capsules,to be administered orally for 24 weeks.
-Part2:BCX7353 capsules,to be administered orally for 28 weeks.

Interventions/Control_2

Drug:BCX7353 capsules, to be administered orally
-Treatment Group 2 (150 mg QD) Parts 1 and 2: two 75 mg capsules of BCX7353
-Part1:BCX7353 capsules,to be administered orally for 24 weeks.
-Part2:BCX7353 capsules,to be administered orally for 28 weeks.

Interventions/Control_3

Drug:BCX7353 capsules, to be administered orally
-Treatment Group 3a (110 mg QD) Part 2: two 55 mg capsules of BCX7353/ Group 3b (150 mg QD) Part 2: two 75 mg capsules of BCX7353
-Part1:two Placebo capsules,to be administered orally for 24 weeks.
-Part2:BCX7353 capsules,to be administered orally for 28 weeks.

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

12

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

-Males and non-pregnant, non-lactating females more than 12 years of age.
-Able to provide written, informed consent. Subjects aged 12 to 17 years must be able to read, understand, and be willing to sign an assent form in addition to a caregiver providing informed consent.
-A clinical diagnosis of HAE Type 1 or Type 2, defined as having a C1 esterase inhibitor (C1 INH) functional level less than 50% and a complement 4 (C4) level below the lower limit of the normal (LLN) reference range, as assessed during the screening period.
-Access to and ability to use an acute treatment for angioedema events approved by the Japan Ministry of Health, Labor, and Welfare (plasma-derived C1 INH or icatibant).
-Subjects must be medically appropriate for on-demand treatment as the sole medicinal management for their HAE during the study, that is, subjects must be medically appropriate to be managed without prophylactic treatments for HAE.
-In the opinion of the investigator, the subject is expected to adequately comply with all required study procedures for the duration of the study. The subject must demonstrate adequate compliance with all study procedures required from the screening visit through randomization, including e-diary recording of angioedema events beginning at the screening visit.

Key exclusion criteria

-Any clinically significant medical or psychiatric condition or medical history that would interfere with the subject's ability to participate in the study or increases the risk to the subject by participating in the study
-Clinically significant abnormal ECG at the screening visit
-Any clinically significant history of angina, myocardial infarction etc. or any other clinically significant cardiovascular abnormality such as poorly controlled hypertension
-Known family history of sudden cardiac death. Family history of sudden death from HAE is not exclusionary
-Any abnormal laboratory or urinalysis parameter at screening that is clinically significant and relevant for this study
-Suspected C1-INH resistance
-Pregnant or planning to become pregnant during the study
-Currently breastfeeding
-Use of androgens or tranexamic acid for prophylaxis of angioedema events within the 28 days prior to the screening visit or initiation during the study
-Use of C1-INH for prophylaxis of angioedema events within the 14 days prior to the screening visit or initiation during the study
-Use of concomitant medications that are metabolized by CYP2D6, CYP2C9, CYP2C19, and CYP3A4 and have a narrow therapeutic range, within 7 days of the baseline visit or planned initiation during the study
-Use of a medication that is clinically known to prolong the QT interval and is metabolized by CYP2D6, CYP2C9, CYP2C19, and/or CYP3A4 7 days prior to the baseline visit or planned initiation during the study
-Use of an angiotensin-converting enzyme inhibitor and a medication that is transported by P-glycoprotein and has a narrow therapeutic range, within 7 days of the baseline visit or planned initiation during the study
-Initiation of an estrogen-containing hormonal contraceptive within 56 days of the screening visit or planned initiation during the study
-Current participation in any other investigational drug study or received another investigational drug within 30 days of the screening visit

Target sample size

24

Name of lead principal investigator

1st name	Sylvia Dobo, MD
Middle name
Last name	Sylvia Dobo, MD

Organization

BioCryst Pharmaceuticals, Inc.

Division name

BioCryst Medical Monitoring team

Zip code

27703

Address

4505 Emperor Boulevard, Suite 200 Durham, NC 27703, USA

TEL

+1-919-859-7905

Email

mmj@biocryst.com

Name of contact person

1st name	Masayuki
Middle name
Last name	Ono

Organization

Covance Japan Co., Ltd.

Division name

Department of Clinical Operations

Zip code

104-6108

Address

Harumi Triton Square Office Tower Y 8F, 1-8-11, Harumi, Chuo-ku, Tokyo ,Japan

TEL

090-1080-7056

Homepage URL

Email

Masayuki.Ono@covance.com

Institute

BioCryst Pharmaceuticals, Inc.

Institute

Department

Personal name

Organization

BioCryst Pharmaceuticals, Inc.

Organization

Division

Category of Funding Organization

Outside Japan

Nationality of Funding Organization

Unites States of America

Co-sponsor

Name of secondary funder(s)

Organization

Shimane University Hospital Institutional Review Board

Address

89-1, Enya-cho, Izumo-shi, Shimane

Tel

0853-23-2111

Email

tiken@med.shimane-u.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2018

Year

11

Month

13

Day

URL releasing protocol

Publication of results

Published

URL related to results and publications

https://pubmed.ncbi.nlm.nih.gov/33247955/

Number of participants that the trial has enrolled

19

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Main results already published

Date of protocol fixation

2018

Year

10

Month

22

Day

Date of IRB

2018

Year

11

Month

14

Day

Anticipated trial start date

2018

Year

12

Month

01

Day

Last follow-up date

2021

Year

06

Month

30

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2018

Year

11

Month

12

Day

Last modified on

2021

Year

10

Month

28

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000039604