Primary: To evaluate the long-term safety of repeated subcutaneous(SC) administrations of lanadelumab in adolescents and adults with nonhistaminergicangioedema with normal C1-INH
ID
Source
Brief title
Condition
- Angioedema and urticaria
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Safety measures, including:
- Adverse events (AEs), including serious adverse events (SAEs) and
adverse events of special interest (AESI)
- Clinical laboratory testing (hematology, clinical chemistry, coagulation,
and urinalysis)
- Vitals signs including blood pressure, heart rate (HR), body
temperature
- Weight and height (height for subjects <18 years old)
- 12-lead ECGs
Secondary outcome
- Number of investigator-confirmed angioedema attacks during the
treatment period
- Number of moderate or severe angioedema attacks during the
treatment period
- Number of high-morbidity angioedema attacks during the treatment
period; a high-morbidity angioedema attack is defined as any attack that
has at least one of the following characteristics: severe, results in
hospitalization (except hospitalization for observation <24 hours),
hemodynamically significant (systolic blood pressure <90 mmHg,
requires intravenous (IV) hydration, or associated with syncope or nearsyncope)
or laryngeal.
- Analysis of pharmacokinetics (PK) effects through measurement of
plasma concentrations of lanadelumab.
- Evaluation of the pharmacodynamic (PD) effects of lanadelumab
through cHMWK and fluorogenic plasma kallikrein (pKal) assay with
FXIIa activation.
- Presence of anti-drug antibodies (ADAs), including evaluation of
neutralizing antibodies (if any confirmed positive anti-drug antibodies
are detected)
- Health-related quality of life assessments will be assessed using the
AE-QoL questionnaire.
- Lanadelumab Injection Report
Safety measures, including:
- AEs, including SAEs and AESIs
- Clinical laboratory testing (hematology, clinical chemistry, coagulation,
and urinalysis)
- Vitals signs including blood pressure (BP), HR, body temperature
- Weight and height (height for subjects <18 years old)
- 12-lead ECGs
Efficacy measures, including:
- Number of investigator-confirmed angioedema attacks during the
treatment period
- Number of moderate or severe angioedema attacks during the
treatment period
- Number of high-morbidity angioedema attacks during the treatment
period; a high-morbidity angioedema attack is defined as any attack that
has at least one of the following characteristics: severe, results in
hospitalization (except hospitalization for observation <24 hours),
hemodynamically significant (systolic blood pressure <90 mmHg,
requires IV hydration, or associated with syncope or near-syncope) or
laryngeal.
Background summary
Unlike HAE Types I and II, there are no approved treatments for the other forms
of non-histaminergic angioedema which are unresponsive to conventional
antihistamine / glucocorticoid treatment. Lanadelumab is expected to fulfil an
unmet medical need for patients with non-histaminergic angioedema with normal
C1-INH and AAE due to C1-INH deficiency by providing a long-term safe,
effective and convenient intervention to prevent angioedema attacks. Based on
the mechanism of action and past case studies with icatibant and ecallantide,
there is a strong scientific rationale to expand the use of lanadelumab.
The targeted indications for lanadelumab (TAK-743/SHP643) currently under study
are:
• prophylaxis to prevent attacks of non-histaminergic angioedema with normal
C1-INH in patients 12 years and older
• prophylaxis to prevent attacks of AAE due to C1-INH deficiency in patients 30
years and older.
Study objective
Primary: To evaluate the long-term safety of repeated subcutaneous
(SC) administrations of lanadelumab in adolescents and adults with
nonhistaminergic
angioedema with normal C1-INH
Study design
An Open-Label Study to Evaluate the Long-Term Safety and Efficacy of
Lanadelumab for
Prevention Against Acute Attacks of Non-histaminergic Angioedema with Normal
C1-Inhibitor (C1-INH)
Intervention
Subjects may receive lanadelumab 300 mg every 2 weeks (q2wks)
or may consider lanadelumab 300 mg q4wks if they have been well-controlled (eg,
attack-free) for 26 consecutive weeks across Study SHP643-303 and Study
TAK-743-3001. The dose frequency change to q4wks will be based on the
investigator*s discretion and consultation with the sponsor*s medical monitor.
Study burden and risks
Subjects will need to complete up to 14 study visits over the course of the
study. Subjects will also receive 1 telephone call from the study team.
Subjects participation in the study will last for 196 days. The subjects will
need to visit the site every 2 - 4 weeks and will, next to the intervention
described above, be subjected to: measurement of vital signs, physical exam,
ECGs, Urine sample collection, blood tests, completing an injection report,
daily angioedema attack diary and study questionnaires
The most common side effects (reported in more than 10% of subjects) were:
- Injection site pain (53.6%),
- Viral upper respiratory tract infection (43.2%),
- Headache (27.7%),
- Upper respiratory tract infection (25.9%),
- Injection site redness (18.2%),
- Injection site bruising (13.6%),
- Joint pain (13.2%),
- Back pain (12.7%),
- Nausea (11.4%),
- Urinary tract infection (11.4%),
- Diarrhea (10.9%),
- Sinusitis (10.9%),
- Abdominal pain (10.5%),
- Fatigue (10.0%),
- Influenza (10.0%),
- Pain in the extremities (10.0%)..
Based on the mechanism of action and past case studies with icatibant
(FIRAZYR®) and ecallantide (KALBITOR®), there is a strong scientific rationale
and high unmet medical need to expand the use of lanadelumab as a prophylactic
therapy for patients with likely bradykinin-mediated angioedema other than Type
I/II HAE.
Hayden Avenue 95
Lexington MA 02421
US
Hayden Avenue 95
Lexington MA 02421
US
Listed location countries
Age
Inclusion criteria
1. Males and females, 12 years of age and older diagnosed with nonhistaminergic
normal C1-INH angioedema at the time of enrollment into
the antecedent Study SHP643-303.
2. Subjects must have completed the treatment period (through Day
182) of Study SHP643-303 without reporting a clinically significant
treatment-emergent adverse event (TEAE) that would preclude
subsequent exposure to lanadelumab.
3. Agree to adhere to the protocol-defined schedule of treatments,
assessments, and procedures.
4. Males, or non-pregnant, non-lactating females who are of childbearing
potential and who agree to be abstinent or agree to comply with the applicable
contraceptive requirements of this protocol for the
duration of the study;
or females of non-childbearing potential, defined as surgically sterile
(status post hysterectomy, bilateral oophorectomy, or bilateral tubal
ligation) or post-menopausal for at least 12 months.
5. The subject (or the subject's parent/legal guardian, if applicable) has
provided written informed consent approved by the institutional review
board/research ethics board/ethics committee (IRB/REB/EC) at any
time prior to study start. If the subject is a minor (ie, <18 years of age),
have a parent/legal guardian who is informed of the nature of the study
provide written informed consent (ie, permission) for the minor to
participate in the study before any study-specific procedures are
performed. Assent will be obtained from minor subjects.
Exclusion criteria
1. Discontinued from Study SHP643-303 after enrollment but before Visit
26 for any reason.
2. Presence of important safety concerns identified in Study SHP643-303
that would preclude participation in this study.
3. Dosing with an investigational product (IP, not including IP defined in
antecedent Study SHP643-303) or exposure to an investigational device
within 4 weeks prior to Day 0.
4. Subject has a known hypersensitivity to the investigational product or
its components.
5. Have any condition (surgical or medical) that, in the opinion of the
investigator or sponsor, may compromise their safety or compliance,
preclude the successful conduct of the study, or interfere with
interpretation of the results (eg, significant pre-existing illness or other
major comorbidities that the investigator considers may confound the
interpretation of study results).
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2019-004823-20-NL |
| Other | IND 116647 |
| CCMO | NL75740.056.21 |