Clinical trial • Phase III • Rare Disease|Endocrinology

ALXN1850 for Hypophosphatasia

Phase III trial of ALXN1850 for Hypophosphatasia.

Overview

Trial Therapeutic Area
Rare Disease|Endocrinology
Trial Disease
Hypophosphatasia
Trial Stage
Phase III
Drug Modality
Peptide/protein/enzyme
Paediatric Trial
Yes

Key dates

Initial CTIS Submission Date
20-11-2023
First CTIS Authorization Date
27-03-2024

Trial design

Randomised, open-label, alxn1850 group: body weight-based dose of alxn1850 every 2 weeks via subcutaneous (sc) injection during the randomized evaluation period; placebo group: placebo every 2 weeks via sc injection during the randomized evaluation period.-controlled Phase III trial in Austria, Belgium, Slovakia and others.

Randomised
Yes
Open Label
Yes
Comparator
ALXN1850 group: body weight-based dose of ALXN1850 every 2 weeks via subcutaneous (SC) injection during the Randomized Evaluation Period; Placebo group: placebo every 2 weeks via SC injection during the Randomized Evaluation Period.
Target Sample Size
88
Trial Duration For Participant
169

Eligibility

Recruits 88 paediatric patients.

Pregnancy Exclusion
Participants who are pregnant, planning to become pregnant, or breastfeeding during the course of the study.
Vulnerable Population
Adolescents (participants ≥ 12 to <18 years) are included. The protocol requires that the participant or their legal representative be capable of giving signed informed consent. For adolescent participants the participant's legal guardian must be willing and able to provide written informed consent and the adolescent participant must be willing to give written informed assent if applicable as determined by the central or local IRB/IEC. (Text from inclusion criteria)

Inclusion criteria

  • {"criterion_text":"- Participant must be ≥ 12 years of age at Day 1\n- Diagnosis of HPP documented in the medical records\n- Must meet 1 of the following criteria: a. Documented ALPL gene variant (pathogenic, likely pathogenic, or variant of unknown significance) from a Clinical Laboratory Improvement Amendam ents (CLIA) or ISO 15189 certified laboratory b. PLP above the upper limit of normal (ULN) during the Screening Period (central or local laboratory results allowed per local regulations)\n- Must meet 1 of the following criteria without a probable cause other than HPP: a.\tSerum ALP activity below the age- and sex-adjusted normal range during the Screening Period, as measured by the Central Laboratory b.\tTwo documented serum ALP activity results, at least 15 days apart, below the age- and sex-adjusted local laboratory normal range during the 24 months before the Day 1 Visit. Note: Local laboratories need to be CLIA or ISO 15189 certified, or have other local equivalent laboratory certification with Alexion’s approval.\n- Two separate 6MWTs at below 85% of the predicted distance (for age, sex, weight, and height) during the Screening Period without a probable cause other than HPP (Note: participants who require assistive walking devices may be included)\n- Female participants of childbearing potential and male participants must follow protocol specified contraception requirements and guidance\n- The participant or their legal representative must be capable of giving signed informed consent as described in the protocol. For adolescent participants, the participant’s legal guardian must be willing and able to provide written informed consent (as defined in the protocol) and the participant must be willing to give written informed assent (if applicable as determined by the central or local Institutional Review Board [IRB]/Institutional [or independent] Ethics Committee [IEC]). Written informed consent/assent includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.\n- Not willing or able to receive asfotase alfa for any reason, including not willing or able to comply with the injection schedule for asfotase alfa."}

Exclusion criteria

  • {"criterion_text":"- History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinological, hematological, neurological disorders, or any other disorders that are capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data as determined by the Investigator\n- Diagnosis of primary or secondary hyperparathyroidism\n- Hypoparathyroidism, unless secondary to HPP\n- Any new fracture within 12 weeks before Day 1 (excluding pseudofractures)\n- Planned surgical intervention which may impact the results of study assessments (in the opinion of the Investigator) during the Randomized Evaluation Period\n- History of allergy or hypersensitivity to any ingredient contained in ALXN1850 or the placebo comparator\n- Body weight < 10 kg during the Screening Period\n- Received asfotase alfa or ALXN1850 at any time before Day 1\n- Received vitamin B6 (including vitamin supplements that contain vitamin B6) within 6 weeks before Day 1\n- Received oral bisphosphonate within 6 months before Day 1\n- Received IV bisphosphonate within 12 months before Day 1\n- Received parathyroid hormone (PTH)-related protein analog (eg, abaloparatide) or PTH analog (eg, teriparatide) within 2 weeks before Day 1\n- Received strontium within 6 months before Day 1\n- Received sclerostin inhibitors within 6 months before Day 1\n- Received growth hormone therapy within 6 months before Day 1\n- Received estrogen agonist/antagonist/inhibitor within 2 months before Day 1 unless used as contraception or for treatment of dysmenorrhea\n- Received a RANKL inhibitor within 6 months before Day 1\n- Participation in any other clinical study involving an investigational study intervention within 30 days before initiation of the first dose of study intervention. Participants involved in interventional studies are not eligible unless the time since last treatment has exceeded 30 days or 5 half-lives of the study intervention, whichever is longer.\n- Corrected calcium levels (adjusted for albumin) below age-adjusted normal range during Screening\n- Serum phosphorus levels below the age-adjusted normal range during Screening\n- Serum 25-hydroxy (25-OH) vitamin D below 20 ng/mL during Screening\n- PTH > ULN of the laboratory reference range during Screening\n- Participants who are unwilling to undergo genetic testing for the ALPL gene.\n- Participants who are pregnant, planning to become pregnant, or breastfeeding during the course of the study.\n- Investigational site personnel involved directly in the study and/or their immediate families. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Change from baseline in 6MWT at the end of the Randomized Evaluation Period (Day 169)","definition_or_measurement_approach":"Change from baseline in the 6-minute walk test (6MWT) at Day 169 (end of Randomized Evaluation Period) as specified in the protocol."}

Secondary endpoints

  • {"endpoint_text":"- Change from baseline in 30-second STS test at the end of the Randomized Evaluation Period (Day 169)\n- Change from baseline in LEFS at the end of the Randomized Evaluation Period (Day 169)\n- Change from baseline in BPI-SF pain severity score at the end of the Randomized Evaluation Period (Day 169)\n- Change from baseline in FACIT-Fatigue score at the end of the Randomized Evaluation Period (Day 169)\n- Change from baseline in Timed Up-and-Go (TUG) at the end of the Randomized Evaluation Period (Day 169)\n- Change from baseline in % Predicted 6MWT at the end of the Randomized Evaluation Period (Day 169)\n- RGI-C Score at the end of the Randomized Evaluation Period (Day 169)\n- RGI-C responder at the end of the Randomized Evaluation Period (Day 169)\n- Change from baseline in RSS at the end of the Randomized Evaluation Period (Day 169)\n- Change from baseline at the end of the Randomized Evaluation Period (Day 169) in: - EuroQoL 5 Dimensions 5 Level (EQ-5D-5L) scale - SF-36v2 PCS score\n- Change from baseline in BPI-SF pain interference score at the end of the Randomized Evaluation Period (Day 169)\n- Change from baseline at the end of the Randomized Evaluation Period (Day 169) in: - PODCI Adolescent – Self-reported - APPT score - Pediatric FACIT-Fatigue score\n- TSQM-9 score at the end of the Randomized Evaluation Period (Day 169)\n- Incidence of TEAEs, TESAEs, AESIs, and AEs leading to study intervention discontinuation or interruption\n- Plasma ALXN1850 Ctrough over time through the end of the Randomized Evaluation Period (Day 169)\n- Plasma ALXN1850 PK parameters in adolescent participants during the Randomized Evaluation Period\n- Observed, change from baseline, and percent change from baseline in plasma concentration of PPi, PLP, PA, and PLP/PL ratio over time through the end of the Randomized Evaluation Period (Day 169)\n- ADA incidence, ADA response categories, and ADA titer, as well as NAb incidence and NAb titer","definition_or_measurement_approach":"Each secondary endpoint is assessed as change from baseline or incidence as specified, generally evaluated at the end of the Randomized Evaluation Period (Day 169) or observed over time through Day 169 as described in the protocol."}

Recruitment

Digital Remote Recruitment
Yes
Planned Sample Size
88
Recruitment Window Months
44
Consent Approach
Informed consent must be provided in writing by the participant or their legal representative. For adolescent participants (≥12 to <18 years) the legal guardian must provide written informed consent and the adolescent must provide written informed assent if required by the central or local IRB/IEC. Subject information and informed consent materials (ICFs and supporting materials) are provided in multiple languages (examples in the dossier: EN, DE, FR, ES, IT, PL, SK, NL-BE) and include supporting materials such as injection instructions and patient information documents.

Methods

  • Half page ad (K2_Recruitment Material_Half Page Ad) - print/digital ad material for patient outreach.
  • Patient Study Fact Sheet (K2_Recruitment Material_Patient Study Fact Sheet) - informational sheet targeted to potential participants and caregivers.
  • Recruitment Brochure/Poster (K2_Recruitment Material_Recruitment Brochure, K2_Recruitment Material_Recruitment Poster) - printed materials for clinics and patient-facing locations.
  • Social posts (K2_Recruitment Material_Social Posts) - social media outreach material.
  • Website/newsletter postings (K2_Recruitment Material_Website Newsletter Posting_long/short) - digital outreach via websites and newsletters.
  • PI-to-Patient invitation to trial letter (K2_Recruitment material_PI-to-Patient Invitation to Trial Letter) - direct clinician-to-patient invitation.
  • Landing page and online materials (K2_Recruitment material_Landing page_DE) - designated online recruitment landing page and digital assets.
  • Training checklist for site staff and site-facing recruitment materials to support consistent local implementation.

Geography

Total Number Of Sites
27
Total Number Of Participants
34

Austria

Earliest CTIS Part Ii Submission Date
29-02-2024
Latest Decision Or Authorization Date
01-04-2024
Processing Time Days
32
Number Of Sites
1
Number Of Participants
2

Sites

Site Name
Hanusch Krankenhaus Der Wiener Gebietskrankenkasse
Department Name
1. Medical Department
Principal Investigator Name
Roland Kocijan
Principal Investigator Email
roland.kocijan@osteologie.lbg.ac.at
Contact Person Name
Roland Kocijan
Number Of Participants
2

Belgium

Earliest CTIS Part Ii Submission Date
04-03-2024
Latest Decision Or Authorization Date
28-03-2024
Processing Time Days
24
Number Of Sites
3
Number Of Participants
4

Sites

Site Name
Antwerp University Hospital
Department Name
Pediatrics/metabolics
Contact Person Name
Francois Eyskens
Contact Person Email
francois.eyskens@uza.be
Site Name
UZ Leuven
Department Name
Metabolic Center
Contact Person Name
David Cassiman
Contact Person Email
david.cassiman@uzleuven.be
Site Name
Association Hospitaliere De Bruxelles Hopital Universitaire Des Enfants Reine Fabiola
Department Name
Nutrition and Metabolism Clinic
Contact Person Name
Corinne De Laet
Contact Person Email
corinne.delaet@hubruxelles.be

Slovakia

Earliest CTIS Part Ii Submission Date
29-02-2024
Latest Decision Or Authorization Date
27-03-2024
Processing Time Days
27
Number Of Sites
1
Number Of Participants
1

Sites

Site Name
University Hospital Bratislava
Department Name
II. Endocrinological outpatient department
Principal Investigator Name
Martin Kužma
Principal Investigator Email
kuzma@ru.unb.sk
Contact Person Name
Martin Kužma
Contact Person Email
kuzma@ru.unb.sk
Number Of Participants
1

Spain

Earliest CTIS Part Ii Submission Date
13-03-2024
Latest Decision Or Authorization Date
01-04-2024
Processing Time Days
19
Number Of Sites
6
Number Of Participants
4

Sites

Site Name
Hospital Universitario Marques De Valdecilla
Department Name
Internal Medicine department
Contact Person Name
José Antonio Riancho Moral
Contact Person Email
rianchoj@unican.es
Site Name
Hospital Del Mar
Department Name
Rheumatology
Contact Person Name
Manuel Ciria Recasens
Contact Person Email
mciria@psmar.cat
Site Name
Hospital Universitario Araba
Department Name
Pediatrics Endocrinology
Contact Person Name
Ignacio Díez López
Contact Person Email
idlcorreo@hotmail.com
Site Name
Hospital Universitario Clinico San Cecilio
Department Name
Endocrinology and Nutrition service
Contact Person Name
Manuel Muñoz Torres
Contact Person Email
mmt@mamuto.es
Site Name
Hospital Universitario De Canarias
Department Name
Rheumatology Department
Contact Person Name
Iván Ferraz Amaro
Contact Person Email
iferrazamaro@hotmail.com
Site Name
Hospital Universitario La Paz
Department Name
Rheumatology Department
Contact Person Name
Maria Pilar Aguado Acín
Contact Person Email
mpilar.aguado@salud.madrid.org

France

Earliest CTIS Part Ii Submission Date
15-01-2024
Latest Decision Or Authorization Date
18-06-2024
Processing Time Days
155
Number Of Sites
2
Number Of Participants
4

Sites

Site Name
Centre Hospitalier Universitaire De Poitiers
Department Name
Rhumatologie
Contact Person Name
Guillaume Larid
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Rhumatologie
Contact Person Name
Christian Roux
Contact Person Email
christian.roux@aphp.fr

Poland

Earliest CTIS Part Ii Submission Date
12-12-2023
Latest Decision Or Authorization Date
02-04-2024
Processing Time Days
112
Number Of Sites
2
Number Of Participants
5

Sites

Site Name
Wojewodzki Specjalistyczny Szpital Dzieciecy Im Sw Ludwika W Krakowie
Department Name
III Oddział Kliniczny Pediatrii, Reumatologii z Pododdzialem Alergologii
Contact Person Name
Zbigniew Zuber
Contact Person Email
zbyszekzuber@interia.pl
Site Name
Instytut Centrum Zdrowia Matki Polki
Department Name
Klinika Endokrynologii i Chorob Metabolicznych
Contact Person Name
Izabela Michalus
Contact Person Email
izabela.michalus@iczmp.edu.pl

Italy

Earliest CTIS Part Ii Submission Date
01-03-2024
Latest Decision Or Authorization Date
27-03-2024
Processing Time Days
26
Number Of Sites
7
Number Of Participants
7

Sites

Site Name
Azienda Ospedaliera Universitaria Integrata Verona
Department Name
Unità di Reumatologia, Dipartimento di Medicina
Contact Person Name
Elena Fracassi
Contact Person Email
elena.fracassi@univr.it
Site Name
Azienda Ospedale-Universita Padova
Department Name
UOC Clinica Medica 1 Dipartimento di Medicina – DIMED
Contact Person Name
Sandro Giannini
Contact Person Email
sandro.giannini@unipd.it
Site Name
Ospedale San Raffaele S.r.l.
Department Name
Unità di Endocrinologia
Contact Person Name
Andrea Giustina
Contact Person Email
giustina.andrea@hsr.it
Site Name
Careggi University Hospital
Department Name
Malattie del Metabolismo Minerale e Osseo
Contact Person Name
Laura Masi
Contact Person Email
masilau@aou-careggi.toscana.it
Site Name
Casa Sollievo Della Sofferenza
Department Name
Dipartimento di Scienze Mediche Endocrinologia
Contact Person Name
Alfredo Scillitani
Contact Person Email
alfredo.scillitani@gmail.com
Site Name
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
Department Name
Endocrinologia, Malattie Rare Center
Contact Person Name
Cristina Eller Vainicher
Site Name
Azienda Ospedaliero Universitaria Pisana
Department Name
U.O. Reumatologia
Contact Person Name
Maurizio Mazzantini
Contact Person Email
mmazzant@int.med.unipi.it

Germany

Earliest CTIS Part Ii Submission Date
19-02-2024
Latest Decision Or Authorization Date
27-03-2024
Processing Time Days
37
Number Of Sites
5
Number Of Participants
7

Sites

Site Name
University Medical Center Hamburg-Eppendorf
Department Name
Kinder-UKE Department of paediatrics, metabolic unit
Contact Person Name
Ania Carolina Muntau
Contact Person Email
muntau@uke.de
Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
Abteilung für Rheumatologie und Klinische Immunologie
Contact Person Name
Frank Buttgereit
Contact Person Email
frank.buttgereit@charite.de
Site Name
Universitaetsklinikum Wuerzburg AöR
Department Name
Orthopädisches Institut, König-Ludwig-Haus
Contact Person Name
Lothar Seefried
Site Name
Praxis für Innere Medizin Stephan Scharla
Department Name
Praxis für Innere Medizin Stephan Scharla
Contact Person Name
Stephan Scharla
Contact Person Email
Dr.Scharla@t-online.de
Site Name
Universitaetsklinikum Bonn AöR
Department Name
Medizinische Klinik und Poliklinik III
Contact Person Name
Valentin Schäfer
Contact Person Email
valentin.schaefer@ukbonn.de

Sponsor

Primary sponsor

Full Name
Alexion Pharmaceuticals Inc.
Organisation Type
Pharmaceutical company
Country Of Registered Address
United States

Investigational products

Investigational Product Name
ALXN1850
Active Substance
ALXN1850
Modality
Peptide/protein/enzyme
Routes Of Administration
Subcutaneous injection
Route
Subcutaneous injection
Frequency
Every 2 weeks
Investigational Product Name
ALXN1850 placebo product
Modality
Other
Frequency
Every 2 weeks

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