Phase 3 Study of ALXN1850 Versus Placebo in Adolescent and Adult Participants With HPP Who Have Not Previously Been Treated With Asfotase Alfa

NCT06079281 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: D8590C00002ALXN1850-HPP-301
• Study Type: interventional
• Target: 124
• Locations: 17 countries
• Sites: 65

Brief Summary

The primary objective of this study is to assess the efficacy of ALXN1850 versus placebo on functional outcomes in adolescent and adult participants with HPP who have not previously been treated with asfotase alfa.

Conditions

Hypophosphatasia

Keywords

Hypophosphatasia; HPP; Asfotase Alfa; ALXN1850

Outcome Measures

Primary Outcomes (1)

• Change from Baseline in 6-Minute Walk Test (6MWT) at the end of the Randomized Evaluation Period (Day 169)

  Baseline, Day 169

Secondary Outcomes (9)

• Change from Baseline in 30-second Sit to Stand (STS) Test Score at the end of the Randomized Evaluation Period (Day 169)

  Baseline, Day 169

• Change from Baseline in Lower Extremity Functional Scale (LEFS) Score at the end of the Randomized Evaluation Period (Day 169)

  Baseline, Day 169

• Change from Baseline in BPI-SF pain severity score at the end of the Randomized Evaluation Period (Day 169) (adult cohort only)

  Baseline, Day 169

• Change from Baseline in FACIT-Fatigue score at the end of the Randomized Evaluation Period (Day 169) (adult cohort only)

  Baseline, Day 169

• Change from Baseline in Timed Up-and-Go (TUG) at the end of the Randomized Evaluation Period (Day 169)

  Baseline, Day 169

Study Arms (2)

Placebo Group

PLACEBO COMPARATOR

During the Randomized Evaluation Period, the placebo group will receive placebo on Day 1, followed by once every 2 weeks (q2w) via SC injection for 24 weeks. Participants will enter the OLE Period and receive bodyweight dependent doses of either 20mg, 35mg, or 50mg of ALXN1850 and continue q2w dosing with ALXN1850 for up to 132 weeks.

Drug: Placebo

ALXN1850 Group

EXPERIMENTAL

Starting at Day 1 of the Randomized Evaluation Period, the ALXN1850 group will receive bodyweight dependent doses of either 20mg, 35mg or 50mg of ALXN1850 once q2w via SC injection, for 24 weeks. Participants will enter the OLE Period and continue q2w dosing with ALXN1850 for up to 132 weeks.

Drug: ALXN1850; Drug: Placebo

Interventions

ALXN1850 DRUG

ALXN1850 will be administered via subcutaneous (SC) injection.

ALXN1850 Group

Placebo DRUG

Placebo will be administered via SC injection.

ALXN1850 Group; Placebo Group

Eligibility Criteria

• Age: 12 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of HPP documented in the medical records
• Must meet 1 of the following criteria:
• Documented ALPL gene variant (pathogenic, likely pathogenic, or variant of unknown significance) from a Clinical Laboratory Improvement Amendments (CLIA) or ISO 15189 certified laboratory (Section 8.7 )
• Plasma PLP above the upper limit of normal (ULN) during the Screening Period (central or local laboratory results allowed per local regulations)
• Must meet 1 of the following criteria without a probably cause other than HPP:
• Serum ALP activity below the age- and sex-adjusted normal range during the screening period as measured by the Central Laboratory
• Two 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.
• 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

You may not qualify if:

• 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
• Diagnosis of primary or secondary hyperparathyroidism
• Hypoparathyroidism, unless secondary to HPP
• Any new fracture within 12 weeks before Day 1 (excluding pseudofractures)
• Planned surgical intervention which may impact the results of study assessments (in the opinion of the Investigator) during the Randomized Evaluation Period
• History of allergy or hypersensitivity to any ingredient contained in ALXN1850 or the placebo comparator (Table 9)

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead

Study Sites (65)

Research Site

Indianapolis, Indiana, 46202, United States

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Garden City, New York, 11530, United States

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Durham, North Carolina, 27705, United States

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Columbus, Ohio, 43203, United States

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Nashville, Tennessee, 37212, United States

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Ciudad de Buenos Aires, C1199, Argentina

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Clayton, 3168, Australia

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Herston, 4029, Australia

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Parkville, 3052, Australia

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St Leonards, 2065, Australia

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Belo Horizonte, 30130-100, Brazil

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Brasília, 71625-009, Brazil

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Recife, 50740-465, Brazil

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Salvador, 40050-410, Brazil

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São Paulo, 01409-902, Brazil

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São Paulo, 05403-900, Brazil

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Calgary, Alberta, T2E 7H7, Canada

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Edmonton, Alberta, T6G 2R7, Canada

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Winnepeg, Manitoba, R3E 3P4, Canada

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Oakville, Ontario, L6M 1M1, Canada

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Trois-Rivières, Quebec, G9A 4P3, Canada

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Beijing, 100039, China

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Beijing, 100730, China

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Changsha, 430033, China

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Chengdu, 610041, China

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Nanchang, 330006, China

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Qingdao, 266035, China

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Shanghai, 201306, China

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Shenzhen, 518053, China

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Paris, 75014, France

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Poitiers, 86000, France

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Bad Reichenhall, 83435, Germany

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Berlin, 10117, Germany

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Bonn, 53127, Germany

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Hamburg, 20251, Germany

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Würzburg, 97074, Germany

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Ashkelon, 7830604, Israel

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Ramat Gan, 52621, Israel

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Florence, 50139, Italy

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Milan, 20122, Italy

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Milan, 20132, Italy

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Padova, 35128, Italy

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Pisa, 56126, Italy

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San Giovanni Rotondo, 71013, Italy

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Verona, 37134, Italy

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Hiroshima, 734-8551, Japan

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Iizuka-shi, 820-8505, Japan

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Osaka, 545-8586, Japan

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Sapporo, 060-8648, Japan

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Yaizu-shi, 425-8505, Japan

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Lodz, 93-338, Poland

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Seoul, 03722, South Korea

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Seoul, 07061, South Korea

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Suwon, 16499, South Korea

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Barcelona, 08003, Spain

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Granada, 18016, Spain

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Madrid, 28046, Spain

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San Cristóbal de La Laguna, 38320, Spain

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Santander, 39008, Spain

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Vitoria-Gasteiz, 01009, Spain

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Taipei, 100, Taiwan

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Taoyuan, 333, Taiwan

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Ankara, 06560, Turkey (Türkiye)

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Yakutiye, 25040, Turkey (Türkiye)

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London, SW170QT, United Kingdom

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Related Links

• Routing the applicable forms for final approval prior to submission by the CTIS Expert

MeSH Terms

Conditions

Hypophosphatasia

Condition Hierarchy (Ancestors)

Metal Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2023
• First Posted: October 12, 2023
• Study Start: January 3, 2024
• Primary Completion: July 9, 2025
• Study Completion (Estimated): March 29, 2028
• Last Updated: May 28, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR

Locations

JP (5); DE (5); ES (6); TW (2); FR (2); KR (3); AU (4); IT (7); AR (1); CA (5); IL (2); CN (8); BR (6); PL (1); GB (1); US (5); TU (2)