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

Alexion Pharmaceuticals

Status and phase: Enrolling; Phase 3

Conditions: Hypophosphatasia

Treatments: Drug: Placebo; Drug: ALXN1850

Study type: Interventional

Funder types: Industry

Identifiers

NCT06079281

ALXN1850-HPP-301 (Other Identifier)

D8590C00002

Details and patient eligibility

About

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.

Enrollment: 114 estimated patients

Sex: All

Ages: 12 to 130 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of HPP documented in the medical records

• Must meet 1 of the following criteria:

  1. 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 )
  2. 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:

  1. Serum ALP activity below the age- and sex-adjusted normal range during the screening period as measured by the Central Laboratory
  2. 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

Exclusion criteria

• 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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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114 participants in 2 patient groups, including a placebo group

Placebo Group

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

ALXN1850 Group

Experimental group

Description:

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.

Treatment:

Drug: ALXN1850

Drug: Placebo