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Hereditary AngioedemaPhase 3APeX-2NCT03485911

Efficacy and Safety Study of BCX7353 as an Oral Treatment for the Prevention of Attacks in HAE

A Phase 3 study testing BCX7353 capsules in people with Hereditary Angioedema and HAE, run by BioCryst Pharmaceuticals at 47 sites in 11 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a phase 3, multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of oral BCX7353 in preventing acute angioedema attacks in patients with Type I and Type II HAE. Read more about this study

Who is it for?
Ages 12 years and older
Conditions the study is for
Hereditary Angioedema, HAE
What is being tested?
BCX7353 capsules
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
121 participants
Where
47 sitesin 11 countries
Study dates
6 Feb 2018to 6 Apr 2022
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • A clinical diagnosis of hereditary angioedema Type 1 or Type 2, defined as having a C1-INH functional level and a C4 level below the lower limit of the normal (LLN) reference range, as assessed during the Screening period.
  • Subject weight of ≥ 40 kg
  • Access to and ability to use one or more acute medications approved by the relevant competent authority for the treatment of acute attacks of HAE
  • Subjects must be medically appropriate for on-demand treatment as the sole medicinal management for their HAE during the study.
  • Subjects must have a specified number of investigator-confirmed attacks during the run-in period of a maximum of 56 days from the Screening visit.
  • Acceptable effective contraception
  • Written informed consent

Who cannot join

  • Pregnancy or breast-feeding
  • Any clinically significant medical condition or medical history that, in the opinion of the Investigator or Sponsor, would interfere with the subject's safety or ability to participate in the study
  • Any laboratory parameter abnormality that, in the opinion of the Investigator, is clinically significant and relevant for this study
  • Severe hypersensitivity to multiple medicinal products or severe hypersensitivity/ anaphylaxis with unclear etiology
  • Use of C1-INH within 14 days or use of androgens or tranexamic acid within 28 days prior to the Screening visit for prophylaxis of HAE attacks, or initiation of these drugs during the study
  • Current participation in any other investigational drug study or received another investigational drug within 30 days of the Screening visit
  • Prior enrollment in a BCX7353 study

Trial locations and contacts

47 sites in 11 countries.

47 sites in 11 countries

United States27 sites
  • Study Center

    Ann Arbor, Michigan, 48106

  • Study center

    Austin, Texas, 78731

  • Study center

    Belleville, New Jersey, 07109

  • Study center

    Birmingham, Alabama, 35209

  • Study Center

    Boston, Massachusetts, 02114

  • Study Site

    Charlotte, North Carolina, 28277

  • Study center

    Chevy Chase, Maryland, 20815

  • Study Center

    Cincinnati, Ohio, 45231

  • Study center

    Clackamas, Oregon, 97015

  • Study center

    Colorado Springs, Colorado, 80907

  • Study center

    Columbus, Ohio, 43235

  • Study center

    Dallas, Texas, 75231

  • Study Center

    Durham, North Carolina, 27705

  • Study Center

    Fair Lawn, New Jersey, 07410

  • Study Center

    Hershey, Pennsylvania, 17033

  • Study center

    Little Rock, Arkansas, 72205

  • Study Center

    New York, New York, 10029

  • Study center

    Piscataway, New Jersey, 08854

  • Study center

    Plymouth, Minnesota, 55446

  • Study Center

    San Antonio, Texas, 78229

  • Study Center

    San Diego, California, 92122

  • Study center

    Santa Monica, California, 90404

  • Study center

    Scottsdale, Arizona, 85251

  • Study Center

    Spokane, Washington, 99202

  • Study Center

    St Louis, Missouri, 63141

  • Study Center

    Tampa, Florida, 33613

  • Study Center

    Walnut Creek, California, 94598

Other trials in United States

United Kingdom4 sites
  • Study Center

    Cambridge, CB2 0QQ

  • Study Center

    Frimley, GU16 7UJ

  • Study Center

    London, E1 2ES

  • Study Center

    Plymouth, PL6 8DH

Other trials in United Kingdom

Canada3 sites
  • Study Center

    Ottawa, Ontario, K1G 6C6

  • Study Center

    Québec, G1V 4W2

  • Study Center

    Toronto, Ontario, M4V 1R2

Other trials in Canada

Spain3 sites
  • Study Center

    Barcelona, 08907

  • Study Center

    Madrid, 28046

  • Study Center

    Seville, 41013

Other trials in Spain

Czechia2 sites
  • Study Center

    Brno, 656 91

  • Study Center

    Pilsen, 30460

Other trials in Czechia

France2 sites
  • Study Center

    Grenoble, 38043

  • Study Center

    Paris, 75012

Other trials in France

Germany2 sites
  • Study Center

    Berlin, 10117

  • Study Center

    Frankfurt, D-60590

Other trials in Germany

Austria1 site
  • Study Center

    Vienna, 1090

Other trials in Austria

Hungary1 site
  • Study Center

    Budapest, H-1225

Other trials in Hungary

North Macedonia1 site
  • Study Center

    Skopje, 1000

Other trials in North Macedonia

Romania1 site
  • Study Center

    Sângeorgiu de Mureș, Jud. Mureș, 547530

Other trials in Romania

About this study

Official 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

This is a phase 3, multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of oral BCX7353 in preventing acute angioedema attacks in patients with Type I and Type II HAE.

Being tested
BCX7353 capsules, Placebo oral capsule
Keywords
BCX7353, Berotralstat
Medical subject headings
Angioedemas, Hereditary

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BCX7353 capsulesDrug

    Also called Berotralstat

    BCX7353 oral capsules administered once daily

  • Placebo oral capsuleDrug

    Matching oral capsules administered once daily

Study groups in NCT03485911
Study groupRoleWhat they receive
BCX7353 110 mg once dailyExperimentalBCX7353 administered as oral capsules once daily
Receives: Drug: BCX7353 capsules
BCX7353 150 mg once dailyExperimentalBCX7353 administered as oral capsules once daily
Receives: Drug: BCX7353 capsules
PlaceboPlacebo comparatorMatching placebo administered as oral capsules once daily
Receives: Drug: Placebo oral capsule

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part 1: The Rate of Investigator-confirmed HAE Attacks During Dosing in the Entire 24-week Treatment Period (Day 1 to Day 168)

    Treatment comparisons between each berotralstat dose and placebo in the rate of investigator-confirmed HAE attacks during the Part 1 dosing period were analyzed using a negative binomial model. The number of investigator-confirmed attacks was included as the dependent variable, the treatment was included as a fixed effect, the stratification variable (baseline attack rate) was included as a covariate, and the logarithm of duration on treatment was included as an offset variable. The estimated attack rate for each treatment group, the treatment differences expressed as the attack rate ratio (berotralstat over placebo rate ratio), and the associated 95% confidence intervals (CIs) were provided from the negative binomial model.

    Measured: 24 weeks

  2. Part 2 & 3: To Evaluate the Long-term Safety and Tolerability of Berotralstat 110 and 150 mg in Subjects With HAE

    The safety data was assessed for the safety population, for subjects who entered Part 2 and Part 3, and includes TEAEs that began in Part 2 or 3, respectively, for these subjects. Safety data for Part 2 and Part 3 is combined to clearly show TEAEs occurring in subjects as the proceeded through the 2 study parts. TEAEs are defined as AEs that occurred on or after first dose of study treatment, whether in Part 1 or 2, and were assigned to the relevant treatment depending on when the TEAE began (Part 2 or Part 3 treatment). No statistical analysis was performed on this safety data.

    Measured: Part 2: 24 weeks (Days 169 to 337). Part 3: 48 weeks (Days 338 to 674).

Secondary outcomes (6)
  1. Part 1: Change From Baseline in Angioedema Quality of Life Questionnaire at Week 24 (Total Score)

    Change in Quality of Life, on a 1-100 scale, where higher scores indicate more impairment and a decrease (change with a negative value) in AE-QoL questionnaire scores indicates an improvement in the subject's QoL. The minimum clinically important difference (MCID) for the AE-QoL questionnaire is -6 (total score). The AE-QoL is only validated for adults; however, data were collected on all adult and adolescent study subjects.

    Measured: Baseline and 24 weeks

  2. Part 1: Proportion of Days With Angioedema Symptoms Through 24 Weeks

    Assessment of proportion of days subjects had angioedema symptoms from expert-confirmed HAE attacks during Part 1.

    Measured: 24 weeks

  3. Part 1: Rate of Expert-confirmed Angioedema Events During Dosing in the Effective Treatment Period

    The rate of expert-confirmed HAE attacks for the effective treatment period gives an analysis of the efficacy of active treatment after berotralstat had reached steady-state concentrations, given the effective half-life of 150 mg berotralstat in Study BCX7353-106 (Study 106) of 89 hours.

    Measured: Day 8 through to 24 weeks (or or the last dose date/time in Part 1 + 24 hours for subjects who discontinued drug in Part 1)

  4. Part 2: To Assess the Effectiveness of Berotralstat Over a 24- to 48 Week Period

    Monthly Attack Rate was defined as the total number of investigator-confirmed HAE attacks experienced during the treatment period adjusted for the length of a month (defined as 28 days) and the number of days the subject was on treatment during that month. The end of Month 6 was defined as the start of Part 2 treatment.

    Baseline investigator-confirmed attack rate was defined as the total number of investigator-confirmed HAE attacks experienced in the period between screening and first dose of study drug adjusted for the length of a month (defined as 28 days) and the number of days during that period.

    Measured: 24 weeks (Days 169 to 337)

  5. To Evaluate Angioedema Quality of Life Questionnaire (Total Score) Following Berotralstat Administration for up to 144 Weeks

    Angioedema-specific QoL was assessed by the AE-QoL, consisting of 4 domains (i.e., functioning, fatigue/mood, fears/shame, and nutrition) and a total score. The AE-QoL scores range from 0 points (best QoL) to 100 points (worst QoL). A decrease (change with a negative value) in AE-QoL questionnaire scores indicates an improvement in the subject's QoL. The minimum clinically important difference (MCID) for the AE-QoL questionnaire is -6 (total score). The AE-QoL was completed by the subjects at each visit starting at baseline, and questions were answered with regard to the previous 28 days. For subjects who received active treatment following placebo, visits were adjusted according to the date of the first dose of active treatment.

    Measured: Up to 144 weeks

  6. To Evaluate Treatment Satisfaction Questionnaire for Medication (TSQM) Following Berotralstat Administration for up to 144 Weeks

    The Treatment Satisfaction Questionnaire for Medication (TSQM) was completed by subjects at baseline and at each study visit until the end of the study. TSQM scores consisted of 14 items of which 13 items were made up of 3 specific scales (Effectiveness, Side Effects, and Convenience) and 1 global satisfaction scale (Global Satisfaction). At baseline, TSQM questionnaires were completed based on subject's satisfaction with usual medications. At all other time points for collection of TSQM, subjects were asked about their level of satisfaction or dissatisfaction with the study drug. Scales scores were calculated for each scale and were transformed into scores ranging from 0 to 100, with higher scores indicating higher satisfaction. TSQM score and corresponding change from baseline values were calculated at each visit. For subjects who received active treatment following placebo, visits were adjusted according to the date of the first dose of active treatment.

    Measured: Up to 144 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Apr 2018
  2. Study start6 Feb 2018
  3. Primary completion10 Apr 2019
  4. Study completion6 Apr 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
121 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03485911
Sponsor's protocol ID
BCX7353-302
Acronym
APeX-2
Status last verified
May 2023
First submitted
15 Mar 2018
Last updated
26 Jun 2023
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Farkas H, Balla Z. A review of berotralstat for the treatment of hereditary angioedema. Expert Rev Clin Immunol. 2023 Feb;19(2):145-153. doi: 10.1080/1744666X.2023.2150611. Epub 2022 Nov 29.

    PubMed 36408587
  • Beard N, Frese M, Smertina E, Mere P, Katelaris C, Mills K. Interventions for the long-term prevention of hereditary angioedema attacks. Cochrane Database Syst Rev. 2022 Nov 3;11(11):CD013403. doi: 10.1002/14651858.CD013403.pub2.

    PubMed 36326435
  • Wedner HJ, Aygoren-Pursun E, Bernstein J, Craig T, Gower R, Jacobs JS, Johnston DT, Lumry WR, Zuraw BL, Best JM, Iocca HA, Murray SC, Desai B, Nagy E, Sheridan WP, Kiani-Alikhan S. Randomized Trial of the Efficacy and Safety of Berotralstat (BCX7353) as an Oral Prophylactic Therapy for Hereditary Angioedema: Results of APeX-2 Through 48 Weeks (Part 2). J Allergy Clin Immunol Pract. 2021 Jun;9(6):2305-2314.e4. doi: 10.1016/j.jaip.2021.03.057. Epub 2021 Apr 15.

    PubMed 33866032
  • Zuraw B, Lumry WR, Johnston DT, Aygoren-Pursun E, Banerji A, Bernstein JA, Christiansen SC, Jacobs JS, Sitz KV, Gower RG, Gagnon R, Wedner HJ, Kinaciyan T, Hakl R, Hanzlikova J, Anderson JT, McNeil DL, Fritz SB, Yang WH, Tachdjian R, Busse PJ, Craig TJ, Li HH, Farkas H, Best JM, Clemons D, Cornpropst M, Dobo SM, Iocca HA, Kargl D, Nagy E, Murray SC, Collis P, Sheridan WP, Maurer M, Riedl MA. Oral once-daily berotralstat for the prevention of hereditary angioedema attacks: A randomized, double-blind, placebo-controlled phase 3 trial. J Allergy Clin Immunol. 2021 Jul;148(1):164-172.e9. doi: 10.1016/j.jaci.2020.10.015. Epub 2020 Oct 21.

    PubMed 33098856

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing BCX7353 capsules in people with Hereditary Angioedema and HAE, run by BioCryst Pharmaceuticals at 47 sites in 11 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 47 sites in United States, United Kingdom, Canada, Spain, Czechia and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Mar 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1: The Rate of Investigator-confirmed HAE Attacks During Dosing in the Entire 24-week Treatment Period (Day 1 to Day 168) (time frame: 24 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03485911, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jun 2023.

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