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Lanadelumab in FXII-associated Cold Autoinflammatory Syndrome (FACAS) (LANA-FXII)

Primary Purpose

Hereditary Autoinflammatory Disease

Status
Recruiting
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
Lanadelumab
Sponsored by
Charite University, Berlin, Germany
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hereditary Autoinflammatory Disease focused on measuring FXII-associated cold autoinflammatory syndrome (FACAS)

Eligibility Criteria

12 Years - 120 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Adults (18 years or older)
  • Documented FXII-associated autoinflammatory disorder (FACAS) by positive genetic analysis result
  • Clinical symptoms of cold-associated wheals, arthralgia, headache, fatigue (FACAS)
  • Able to read, understand and willing to sign the informed consent form and abide with study procedures
  • Males and females who are fertile and sexually active must adhere to contraception requirements for the duration of the study as follows:
  • Females of childbearing potential must agree to be abstinent or else use any two of the following medically acceptable forms of contraception from the screening period through 30 days after the final study visit: progestin-only oral contraceptive, condom with or without spermicidal jelly, diaphragm or cervical cap with spermicidal jelly, or intra-uterine device (IUD, all types). Female participants whose male partner has had a vasectomy must agree to use one additional form of medically acceptable contraception.
  • 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 do not require contraception during the study.
  • Males, including males who are surgically sterile (post vasectomy), with female partners of childbearing potential must agree to be abstinent or else use a medically acceptable form of contraception from the screening period through 60 days after the last IMP injection.

Exclusion Criteria:

  • 1. Any other forms of urticaria or angioedema not related to genetic mutations within the FXII gene 2. Concurrent/ongoing treatment with biologics or recent treatment (less than 5 half-lives) 3. Concurrent/ongoing treatment with anakinra within 7 days prior to screening, with canakinumab within 100 days prior to screening 4. Concurrent/ongoing treatment with oral/parenteral corticosteroids greater than 10 mg/d within 2 weeks prior to screening 5. Concurrent/ongoing treatment with other immunosuppressives within 4 weeks or 5 half-lives prior to screening, whichever is longer 6. Treatment with a live (attenuated) virus vaccine within 4 weeks prior to Baseline visit 7. Exposure to angiotensin-converting enzyme (ACE) inhibitors or any estrogen-containing medications with systemic absorption (such as oral contraceptives or hormonal replacement therapy) within 4 weeks prior to screening.

    8. Use of prophylactic therapy with C1-INH, attenuated androgens, or antifibrinolytics within 2 weeks prior to the start of the treatment period (Day 0).

    9. Any of the following liver function test abnormalities:

    • alanine aminotransferase (ALT) > 3x upper limit of normal, or
    • aspartate aminotransferase (AST) > 3x upper limit of normal, or
    • total bilirubin > 2x upper limit of normal (unless the bilirubin elevation is a result of Gilbert's Syndrome).

      10. Pregnancy or breastfeeding. 11. Subject has any condition that, in the opinion of the Investigator or Sponsor, may compromise their safety or compliance, preclude successful conduct of the study, or interfere with interpretation of the results (e.g., history of substance abuse or dependence, a significant pre-existing illness or other major comorbidity that the Investigator considers may confound the interpretation of study results).

      12. Significant medical condition rendering the patient immunocompromised or not suitable for a clinical trial.

      13. Enrollment in another investigational treatment or device study or use of an investigational agent, or less than 4 weeks or 5 half-lives, whichever is longer, since end of another investigational device or drug trial.

      14. Patients with known hypersensitivity to any constituent of the products of lanadelumab.

      15. Dementia, altered mental status, or any psychiatric condition, or stay in an institution further to an official or court order that would prohibit the understanding or rendering of informed consent or participation in the study.

      16. Subjects who are study site employees, or immediate family members of a study site or sponsor employee.

Sites / Locations

  • Charite University, Berlin, GermanyRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Lanadelumab

Arm Description

Outcomes

Primary Outcome Measures

Change in total disease activity score as assessed by daily health assessment form (DHAF) questionnaire following lanadelumab treatment
Patient-reported total disease activity is assessed by a disease-specific daily health assessment form (FXII-associated Cold autoinflammatory Syndrome daily Health assessment form; FACAS-DHAF) grading the severity of 5 key symptoms of FACAS: urticarial rash, fatigue, chills/fever, arthralgia and headache (scale 0=no symptoms to 50=max. of symptoms).

Secondary Outcome Measures

Change in urticarial rash disease activity score as assessed by daily health assessment form (DHAF) questionnaire following lanadelumab treatment
Patient-reported urticarial rash disease activity is assessed by a disease-specific daily health assessment form (FXII-associated Cold autoinflammatory Syndrome daily Health assessment form; FACAS-DHAF; scale 0=no symptoms to 10=max. of symptoms)
Change in fatigue disease activity score as assessed by daily health assessment form (DHAF) questionnaire following lanadelumab treatment
Patient-reported fatigue disease activity is assessed by a disease-specific daily health assessment form (FXII-associated Cold autoinflammatory Syndrome daily Health assessment form; FACAS-DHAF; scale 0=no symptoms to 10=max. of symptoms)
Change in chills/fever disease activity score as assessed by daily health assessment form (DHAF) questionnaire following lanadelumab treatment
Patient-reported chills/fever disease activity is assessed by a disease-specific daily health assessment form (FXII-associated Cold autoinflammatory Syndrome daily Health assessment form; FACAS-DHAF;scale 0=no symptoms to 10=max. of symptoms)
Change in arthralgia disease activity score as assessed by daily health assessment form (DHAF) questionnaire following lanadelumab treatment
Patient-reported arthralgia disease activity is assessed by a disease-specific daily health assessment form (FXII-associated Cold autoinflammatory Syndrome daily Health assessment form; FACAS-DHAF; scale 0=no symptoms to 10=max. of symptoms)
Change in headache disease activity score as assessed by daily health assessment form (DHAF) questionnaire following lanadelumab treatment
Patient-reported headache disease activity is assessed by a disease-specific daily health assessment form (FXII-associated Cold autoinflammatory Syndrome daily Health assessment form; FACAS-DHAF; scale 0=no symptoms to 10=max. of symptoms)
Change in total disease activity score as assessed by daily health assessment form (DHAF) questionnaire following lanadelumab Treatment over Long-term use
Patient-reported total disease activity is assessed by a disease-specific daily health assessment form (FXII-associated Cold autoinflammatory Syndrome daily Health assessment form; FACAS-DHAF; scale 0=no symptoms to 50=max. of symptoms
Change in inflammation markers following lanadelumab Treatment
Assessment of CRP levels
Change in inflammation markers following lanadelumab Treatment
Assessment of ESR levels
Change in inflammation markers following lanadelumab Treatment
Assessment of SAA levels
Change in inflammation markers following lanadelumab Treatment
Assessment of S100 A8/9 levels
Change in dermatology-specific quality-of-life following lanadelumab Treatment
assessed by Dermatology Life Quality Index (DLQI); scale 0=no impairment to 30=max. impairment
Changes in generic Health-related quality-of-life
assessed by 36-Item Short Form Health Survey (SF-36); scale 0=max. impairment to 100=no impairment (best Quality of life)
Incidence of of Treatment-emergent adverse Events, abnormal physical examination, abnormal Routine safety laboratory assessments, abnormal vital signs (safety and tolerability)
Safety of lanadelumab Treatment is assessed by physical examination, routine safety laboratory assessments, vital signs, and adverse Event reporting.
Change in physician global assessment following lanadelumab Treatment as assessed by verbal rating scale
Verbal Rating scale assesses overall Symptoms from 0-10 (0=no symptoms; 10=very severe symptoms)
Changes of plasma levels of potential biomarkers following Lanadelumab treatment
Potential biomarkers include Plasma FXII Levels
Changes of plasma levels of potential biomarkers following Lanadelumab treatment
Potential biomarkers include Plasma prekallikrein Levels
Changes of plasma levels of potential biomarkers following Lanadelumab treatment
Potential biomarkers include Plasma cHMWK Levels
Changes of plasma levels of potential biomarkers following Lanadelumab treatment
Potential biomarkers include IL-1ß release from donor PBMCs

Full Information

First Posted
February 13, 2020
Last Updated
January 31, 2023
Sponsor
Charite University, Berlin, Germany
Collaborators
Shire International GmbH
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1. Study Identification

Unique Protocol Identification Number
NCT04278885
Brief Title
Lanadelumab in FXII-associated Cold Autoinflammatory Syndrome (FACAS)
Acronym
LANA-FXII
Official Title
Factor XII-associated Cold Autoinflammatory Syndrome (FACAS) Linked to Kallikrein-kinin Pathology: Proof of Concept Treatment With Lanadelumab (DX-2930)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 5, 2020 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Charite University, Berlin, Germany
Collaborators
Shire International GmbH

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a Phase 2, exploratory, proof-of-concept, single-center, open-label pilot study to assess the effects and safety of Lanadelumab in patients with FXII-associated cold autoinflammatory syndrome (FACAS).
Detailed Description
Factor XII is a serine protease with diverse functions that participates in coagulation, fibrinolysis, complement and contact system activation. So far, mutations in the factor XII gene were linked to the rare coagulation disorder Hagemann factor deficiency and hereditary angioedema (FXII-HAE). The investigators recently identified a novel FXII mutation in a 4-generation family with profound contact system activation and an autoinflammatory clinical phenotype. Lanadelumab is a specific kallikrein Inhibitor that is known to prevent clinical symptoms and contact system activation in hereditary angioedema. This study aims at assessing the clinical effects and safety of Lanadelumab in patients with FXII-associated cold autoinflammatory syndrome (FACAS).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hereditary Autoinflammatory Disease
Keywords
FXII-associated cold autoinflammatory syndrome (FACAS)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
exploratory, proof-of-concept, single-center, open-label pilot study
Masking
None (Open Label)
Allocation
N/A
Enrollment
3 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Lanadelumab
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Lanadelumab
Other Intervention Name(s)
DX-2930
Intervention Description
300mg Lanadelumab s.c. administration every 2 weeks
Primary Outcome Measure Information:
Title
Change in total disease activity score as assessed by daily health assessment form (DHAF) questionnaire following lanadelumab treatment
Description
Patient-reported total disease activity is assessed by a disease-specific daily health assessment form (FXII-associated Cold autoinflammatory Syndrome daily Health assessment form; FACAS-DHAF) grading the severity of 5 key symptoms of FACAS: urticarial rash, fatigue, chills/fever, arthralgia and headache (scale 0=no symptoms to 50=max. of symptoms).
Time Frame
weeks 9 to 12 compared to weeks -4 to -1 (baseline)
Secondary Outcome Measure Information:
Title
Change in urticarial rash disease activity score as assessed by daily health assessment form (DHAF) questionnaire following lanadelumab treatment
Description
Patient-reported urticarial rash disease activity is assessed by a disease-specific daily health assessment form (FXII-associated Cold autoinflammatory Syndrome daily Health assessment form; FACAS-DHAF; scale 0=no symptoms to 10=max. of symptoms)
Time Frame
weeks 9 to 12 and weeks 24 to 28, each compared to weeks -4 to -1 (baseline)
Title
Change in fatigue disease activity score as assessed by daily health assessment form (DHAF) questionnaire following lanadelumab treatment
Description
Patient-reported fatigue disease activity is assessed by a disease-specific daily health assessment form (FXII-associated Cold autoinflammatory Syndrome daily Health assessment form; FACAS-DHAF; scale 0=no symptoms to 10=max. of symptoms)
Time Frame
weeks 9 to 12 and weeks 24 to 28, each compared to weeks -4 to -1 (baseline)
Title
Change in chills/fever disease activity score as assessed by daily health assessment form (DHAF) questionnaire following lanadelumab treatment
Description
Patient-reported chills/fever disease activity is assessed by a disease-specific daily health assessment form (FXII-associated Cold autoinflammatory Syndrome daily Health assessment form; FACAS-DHAF;scale 0=no symptoms to 10=max. of symptoms)
Time Frame
weeks 9 to 12 and weeks 24 to 28, each compared to weeks -4 to -1 (baseline)
Title
Change in arthralgia disease activity score as assessed by daily health assessment form (DHAF) questionnaire following lanadelumab treatment
Description
Patient-reported arthralgia disease activity is assessed by a disease-specific daily health assessment form (FXII-associated Cold autoinflammatory Syndrome daily Health assessment form; FACAS-DHAF; scale 0=no symptoms to 10=max. of symptoms)
Time Frame
weeks 9 to 12 and weeks 24 to 28, each compared to weeks -4 to -1 (baseline)
Title
Change in headache disease activity score as assessed by daily health assessment form (DHAF) questionnaire following lanadelumab treatment
Description
Patient-reported headache disease activity is assessed by a disease-specific daily health assessment form (FXII-associated Cold autoinflammatory Syndrome daily Health assessment form; FACAS-DHAF; scale 0=no symptoms to 10=max. of symptoms)
Time Frame
weeks 9 to 12 and weeks 24 to 28, each compared to weeks -4 to -1 (baseline)
Title
Change in total disease activity score as assessed by daily health assessment form (DHAF) questionnaire following lanadelumab Treatment over Long-term use
Description
Patient-reported total disease activity is assessed by a disease-specific daily health assessment form (FXII-associated Cold autoinflammatory Syndrome daily Health assessment form; FACAS-DHAF; scale 0=no symptoms to 50=max. of symptoms
Time Frame
weeks 24 to 28 compared to weeks -4 to -1 (baseline)
Title
Change in inflammation markers following lanadelumab Treatment
Description
Assessment of CRP levels
Time Frame
from Baseline to week 12 and week 28
Title
Change in inflammation markers following lanadelumab Treatment
Description
Assessment of ESR levels
Time Frame
from Baseline to week 12 and week 28
Title
Change in inflammation markers following lanadelumab Treatment
Description
Assessment of SAA levels
Time Frame
from Baseline to week 12 and week 28
Title
Change in inflammation markers following lanadelumab Treatment
Description
Assessment of S100 A8/9 levels
Time Frame
from Baseline to week 12 and week 28
Title
Change in dermatology-specific quality-of-life following lanadelumab Treatment
Description
assessed by Dermatology Life Quality Index (DLQI); scale 0=no impairment to 30=max. impairment
Time Frame
from Baseline to week 12 and week 28
Title
Changes in generic Health-related quality-of-life
Description
assessed by 36-Item Short Form Health Survey (SF-36); scale 0=max. impairment to 100=no impairment (best Quality of life)
Time Frame
from Baseline to week 12 and week 28
Title
Incidence of of Treatment-emergent adverse Events, abnormal physical examination, abnormal Routine safety laboratory assessments, abnormal vital signs (safety and tolerability)
Description
Safety of lanadelumab Treatment is assessed by physical examination, routine safety laboratory assessments, vital signs, and adverse Event reporting.
Time Frame
from Baseline to end of study (week 36 follow-up)
Title
Change in physician global assessment following lanadelumab Treatment as assessed by verbal rating scale
Description
Verbal Rating scale assesses overall Symptoms from 0-10 (0=no symptoms; 10=very severe symptoms)
Time Frame
from Baseline to week 12 and week 28
Title
Changes of plasma levels of potential biomarkers following Lanadelumab treatment
Description
Potential biomarkers include Plasma FXII Levels
Time Frame
from Baseline to week 28
Title
Changes of plasma levels of potential biomarkers following Lanadelumab treatment
Description
Potential biomarkers include Plasma prekallikrein Levels
Time Frame
from Baseline to week 28
Title
Changes of plasma levels of potential biomarkers following Lanadelumab treatment
Description
Potential biomarkers include Plasma cHMWK Levels
Time Frame
from Baseline to week 28
Title
Changes of plasma levels of potential biomarkers following Lanadelumab treatment
Description
Potential biomarkers include IL-1ß release from donor PBMCs
Time Frame
from Baseline to week 28

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Adolescents (12 - 17 years) and adults (18 years or older) Documented FXII-associated autoinflammatory disorder (FACAS) by positive genetic analysis result Clinical symptoms of cold-associated wheals, arthralgia, headache, fatigue (FACAS) Able to read, understand and willing to sign the informed consent form and abide with study procedures Males and females who are fertile and sexually active must adhere to contraception requirements for the duration of the study as follows: Females of childbearing potential must agree to be abstinent or else use any two of the following medically acceptable forms of contraception from the screening period through 30 days after the final study visit: progestin-only oral contraceptive, condom with or without spermicidal jelly, diaphragm or cervical cap with spermicidal jelly, or intra-uterine device (IUD, all types). Female participants whose male partner has had a vasectomy must agree to use one additional form of medically acceptable contraception. 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 do not require contraception during the study. Males, including males who are surgically sterile (post vasectomy), with female partners of childbearing potential must agree to be abstinent or else use a medically acceptable form of contraception from the screening period through 60 days after the last IMP injection. Exclusion Criteria: 1. Any other forms of urticaria or angioedema not related to genetic mutations within the FXII gene 2. Concurrent/ongoing treatment with biologics or recent treatment (less than 5 half-lives) 3. Concurrent/ongoing treatment with anakinra within 7 days prior to screening, with canakinumab within 100 days prior to screening 4. Concurrent/ongoing treatment with oral/parenteral corticosteroids greater than 10 mg/d within 2 weeks prior to screening 5. Concurrent/ongoing treatment with other immunosuppressives within 4 weeks or 5 half-lives prior to screening, whichever is longer 6. Treatment with a live (attenuated) virus vaccine within 4 weeks prior to Baseline visit 7. Exposure to angiotensin-converting enzyme (ACE) inhibitors or any estrogen-containing medications with systemic absorption (such as oral contraceptives or hormonal replacement therapy) within 4 weeks prior to screening. 8. Use of prophylactic therapy with C1-INH, attenuated androgens, or antifibrinolytics within 2 weeks prior to the start of the treatment period (Day 0). 9. Any of the following liver function test abnormalities: alanine aminotransferase (ALT) > 3x upper limit of normal, or aspartate aminotransferase (AST) > 3x upper limit of normal, or total bilirubin > 2x upper limit of normal (unless the bilirubin elevation is a result of Gilbert's Syndrome). 10. Pregnancy or breastfeeding. 11. Subject has any condition that, in the opinion of the Investigator or Sponsor, may compromise their safety or compliance, preclude successful conduct of the study, or interfere with interpretation of the results (e.g., history of substance abuse or dependence, a significant pre-existing illness or other major comorbidity that the Investigator considers may confound the interpretation of study results). 12. Significant medical condition rendering the patient immunocompromised or not suitable for a clinical trial. 13. Enrollment in another investigational treatment or device study or use of an investigational agent, or less than 4 weeks or 5 half-lives, whichever is longer, since end of another investigational device or drug trial. 14. Patients with known hypersensitivity to any constituent of the products of lanadelumab. 15. Dementia, altered mental status, or any psychiatric condition, or stay in an institution further to an official or court order that would prohibit the understanding or rendering of informed consent or participation in the study. 16. Subjects who are study site employees, or immediate family members of a study site or sponsor employee.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Karoline Krause, Prof.
Phone
+4930450518336
Email
karoline.krause@charite.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Karoline Krause, Prof.
Organizational Affiliation
Charité University, Berlin, Germany
Official's Role
Principal Investigator
Facility Information:
Facility Name
Charite University, Berlin, Germany
City
Berlin
ZIP/Postal Code
12203
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Krause Karoline, Prof.
Phone
004930450518336
Email
karoline.krause@charite.de

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Lanadelumab in FXII-associated Cold Autoinflammatory Syndrome (FACAS)

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