ALXN1850 for Hypophosphatasia

Inclusion criteria

• {"criterion_text":"- Participant must be ≥ 2 and < 12 years of age at Day 1\n- Diagnosis of HPP documented in the medical records, and the following criteria fulfilled without other probable cause than HPP: a.\tPresence of HPP-related rickets on skeletal X-rays during the Screening Period, with a minimum Rickets Severity Score (RSS) of 1.0 AND b.\tSerum ALP activity below the age- and sex-adjusted normal range during the Screening Period as measured by the Central Laboratory OR 2 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 Clinical Laboratory Improvement Amendments (CLIA) or ISO 15189 certified, or have other local equivalent laboratory certification with Alexion’s approval.\n- Must meet 1 of the following criteria: a.\tDocumented ALPL gene variant (pathogenic, likely pathogenic, or variant of unknown significance) from a CLIA or ISO 15189 certified laboratory (Section 8.7) b.\tPLP above the upper limit of normal (ULN) during the Screening Period (central or local laboratory results allowed per local regulations)\n- Tanner stage 2 or less during the Screening Period\n- Female participants of childbearing potential and male participants must follow contraception requirements and guidance as defined in the protocol.\n- 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 the protocol."}

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- Received oral bisphosphonate within 6 months before Day 1\n- Received IV bisphosphonate within 12 months before Day 1\n- Received a 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 or estrogen agonist/antagonist/inhibitor within 2 months before Day 1 unless used as contraception or for treatment of dysmenorrhea\n- Received a receptor activator of nuclear factor kappa B ligand (RANKL) inhibitor within 6 months before Day 11\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- Diagnosis of primary or secondary hyperparathyroidism\n- Serum phosphorus levels below the age-adjusted normal range during Screening\n- Evidence of a treatable form of rickets (eg, vitamin D deficiency) other than HPP 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.\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"}

Primary endpoints

• {"endpoint_text":"- RGI-C score at the end of the Randomized Evaluation Period (Day 169)","definition_or_measurement_approach":"RGI-C score measured at Day 169 (end of Randomized Evaluation Period) as stated in endpoint description."}

Secondary endpoints

• {"endpoint_text":"- Change from baseline in RSS at the end of the Randomized Evaluation Period (Day 169)","definition_or_measurement_approach":"Change from baseline in Rickets Severity Score (RSS) measured at Day 169."}
• {"endpoint_text":"- \"Change from baseline at the end of the Randomized Evaluation Period (Day 169) in the following: -\t6MWT (≥ 5 years of age) -\t% Predicted 6MWT (≥ 5 years of age) -\tBOT-2 (≥ 4 years of age) -\tPDMS-3 (< 4 years of age)\"","definition_or_measurement_approach":"Change from baseline at Day 169 in specified functional tests: 6-minute walk test (6MWT) and % predicted 6MWT for ≥5 years; BOT-2 for ≥4 years; PDMS-3 for <4 years."}
• {"endpoint_text":"- RGI-C responder at the end of the Randomized Evaluation Period (Day 169)","definition_or_measurement_approach":"Responder status based on RGI-C at Day 169 as defined in protocol."}
• {"endpoint_text":"- Change from baseline at the end of the Randomized Evaluation Period (Day 169) in the following: -\tEQ-5D-Y health state score (≥ 8 years of age) -\tEQ-5D-Y-Proxy Version 1 health state score (≥ 4 to < 8 years of age) -\tPODCI-Parent global function score -\tAPPT score (≥ 8 years of age) -\tPediatric FACIT-Fatigue score (≥ 8 years of age) -Pediatric FACIT-Fatigue Proxy score (≥ 2 to < 8 years of age)","definition_or_measurement_approach":"Change from baseline at Day 169 in health-related quality of life and symptom scales (EQ-5D-Y, EQ-5D-Y Proxy, PODCI, APPT, Pediatric FACIT-Fatigue and proxy versions) per age-specified instruments."}
• {"endpoint_text":"- TSQM-9 score at the end of the Randomized Evaluation Period (Day 169)","definition_or_measurement_approach":"Treatment Satisfaction Questionnaire for Medication (TSQM-9) score at Day 169."}
• {"endpoint_text":"- Incidence of TEAEs, TESAEs, AESIs, and AEs leading to study intervention discontinuation or interruption","definition_or_measurement_approach":"Safety reporting of treatment-emergent adverse events, serious adverse events, adverse events of special interest, and AEs causing discontinuation/interruption throughout the study."}
• {"endpoint_text":"- \"Estimation of PK parameters and accumulation ratios -\tALXN1850 PK: AUC(0-24h) at Day 1, AUC(0-24h) and C(trough) at D85; accumulation ratio of D85 to Day 1 based on AUC(0-24h)\"","definition_or_measurement_approach":"PK parameters: AUC(0-24h) Day 1, AUC(0-24h) and trough concentration at Day 85; accumulation ratio D85/Day1 based on AUC(0-24h)."}
• {"endpoint_text":"- Plasma ALXN1850 C(trough) over time through the end of the Randomized Evaluation Period (Day 169)","definition_or_measurement_approach":"Plasma trough concentrations measured over time through Day 169."}
• {"endpoint_text":"- \"Estimation of PD parameters -\tObserved, change, and percent changes in plasma concentration of PPi, PLP, PA, and PLP/PL ratio from baseline through the end of the Randomized Evaluation Period (Day 169)\"","definition_or_measurement_approach":"PD measurements: plasma PPi, PLP, PA, PLP/PL ratio observed and percent changes from baseline through Day 169."}
• {"endpoint_text":"- ADA incidence, ADA response categories, and ADA titer, as well as NAb incidence and NAb titers","definition_or_measurement_approach":"Immunogenicity assessments: anti-drug antibody incidence, response categories, titers, and neutralizing antibody incidence/titers during study."}

Methods

• Recruitment Brochure (K2_Recruitment material_Recruitment Brochure) - patient/caregiver-facing brochure materials (multiple language versions) used to inform and recruit pediatric participants and caregivers; country-specific brochures provided (e.g., Belgium and other participating Member States).
• Recruitment Poster (K2_Recruitment material_Recruitment Poster) - posters for site/display to reach patients/caregivers in clinic settings (multiple language versions).
• Social posts and social media materials (K2_Recruitment Material_Social Posts) - digital/social channels targeting patient communities and caregivers to raise awareness.
• Website/Newsletter postings (K2_Recruitment Material_Website Newsletter Posting Long/Short) - content for websites and newsletters to reach caregivers and patient communities.
• Half-page ad (K2_Recruitment Material_Half Page Ad) - print/digital advertisement material for outreach.
• Patient Study Fact Sheet / Patient Study Fact Sheet Brochure - informational leaflet for potential participants and caregivers summarizing trial purpose and participation requirements.
• Patient Invitation to Trial Letter / Patient Invitation documents - direct invitation materials for potential participants identified through clinics.
• Assent tools and age-specific recruitment materials (Assent Tool Ages 5-8, Assent Tool Ages 9-12, Assent materials for 6-11yo and 8-12y) - tools to support assent and engagement of pediatric participants.
• ICF tools and caregiver information sheets (L1_SIS and ICF caregiver, L1_SIS and ICF pediatric participant) - informed consent materials provided to guardians and caregivers.

France

Earliest CTIS Part Ii Submission Date

11-12-2023

Latest Decision Or Authorization Date

04-03-2024

Processing Time Days

84

Number Of Sites

2

Number Of Participants

1

Italy

Earliest CTIS Part Ii Submission Date

05-02-2024

Latest Decision Or Authorization Date

27-02-2024

Processing Time Days

22

Number Of Sites

3

Number Of Participants

3

Belgium

Earliest CTIS Part Ii Submission Date

10-01-2024

Latest Decision Or Authorization Date

04-07-2025

Processing Time Days

541

Number Of Sites

1

Number Of Participants

1

Spain

Earliest CTIS Part Ii Submission Date

11-12-2023

Latest Decision Or Authorization Date

08-07-2025

Processing Time Days

575

Number Of Sites

2

Number Of Participants

1

Poland

Earliest CTIS Part Ii Submission Date

27-11-2024

Latest Decision Or Authorization Date

09-07-2025

Processing Time Days

224

Number Of Sites

2

Number Of Participants

3

Sweden

Earliest CTIS Part Ii Submission Date

17-09-2024

Latest Decision Or Authorization Date

04-07-2025

Processing Time Days

290

Number Of Sites

1

Number Of Participants

1

Finland

Earliest CTIS Part Ii Submission Date

28-01-2025

Latest Decision Or Authorization Date

07-07-2025

Processing Time Days

160

Number Of Sites

1

Number Of Participants

2

Romania

Earliest CTIS Part Ii Submission Date

09-12-2024

Latest Decision Or Authorization Date

09-07-2025

Processing Time Days

212

Number Of Sites

1

Number Of Participants

1

Primary sponsor

Full Name

Alexion Pharmaceuticals Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States