Clinical trial NCT06079281: Phase 3 Study of ALXN1850 Versus Placebo in Adolescent and Adult Participants With HPP Who Have Not Previously Been Treated With Asfotase Alfa
Official title: A Phase 3, Randomized, Double-blinded, Placebo-controlled, Multicenter Study to Evaluate Efficacy and Safety of ALXN1850 (Recombinant Alkaline Phosphatase) Administered Subcutaneously in Adolescent (12 to < 18 Years of Age) and Adult Participants With Hypophosphatasia Who Have Not Previously Been Treated With Asfotase Alfa
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Hypophosphatasia
Keywords: Hypophosphatasia
HPP
Asfotase Alfa
ALXN1850
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2023-10-12
Enrollment: 124
Sex: ALL
Minimum age (years): 12
Maximum age (years): 130
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Change from Baseline in 6-Minute Walk Test (6MWT) at the end of the Randomized Evaluation Period (Day 169)
timeFrame: Baseline, Day 169
Secondary outcomes:
measure: Change from Baseline in 30-second Sit to Stand (STS) Test Score at the end of the Randomized Evaluation Period (Day 169)
timeFrame: Baseline, Day 169
measure: Change from Baseline in Lower Extremity Functional Scale (LEFS) Score at the end of the Randomized Evaluation Period (Day 169)
timeFrame: Baseline, Day 169
measure: Change from Baseline in BPI-SF pain severity score at the end of the Randomized Evaluation Period (Day 169) (adult cohort only)
timeFrame: Baseline, Day 169
measure: Change from Baseline in FACIT-Fatigue score at the end of the Randomized Evaluation Period (Day 169) (adult cohort only)
timeFrame: Baseline, Day 169
measure: Change from Baseline in Timed Up-and-Go (TUG) at the end of the Randomized Evaluation Period (Day 169)
timeFrame: Baseline, Day 169
measure: Change from Baseline in Percent Predicted 6MWT at the end of the Randomized Evaluation Period (Day 169)
timeFrame: Baseline, Day 169
measure: Radiographic Global Impression of Change (RGI-C) Score at the end of the Randomized Evaluation Period (Day 169)
timeFrame: Day 169
measure: RGI-C Responder at the end of the Randomized Evaluation Period (Day 169)
timeFrame: Day 169
measure: Change from Baseline in Rickets Severity Score (RSS) at the end of the Randomized Evaluation Period (Day 169)
timeFrame: Baseline, Day 169
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Research Site
state: Indiana
city: Garden City
country: United States
facility: Research Site
state: New York
city: Durham
country: United States
facility: Research Site
state: North Carolina
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Buenos Aires
country: Argentina
facility: Research Site
city: Clayton
country: Australia
facility: Research Site
city: Herston
country: Australia
facility: Research Site
city: Parkville
country: Australia
facility: Research Site
city: st Leonards
country: Australia
facility: Research Site
city: Belo Horizonte
country: Brazil
facility: Research Site
city: Brasilia
country: Brazil
facility: Research Site
city: Recife
country: Brazil
facility: Research Site
city: Salvador
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: São Paulo
country: Brazil
facility: Research Site
city: Calgary
country: Canada
facility: Research Site
state: Alberta
city: Edmonton
country: Canada
facility: Research Site
state: Alberta
city: Winnepeg
country: Canada
facility: Research Site
state: Manitoba
city: Oakville
country: Canada
facility: Research Site
state: Ontario
city: Trois-Rivières
country: Canada
facility: Research Site
state: Quebec
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Nanchang
country: China
facility: Research Site
city: Qingdao
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shenzhen
country: China
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Poitiers
country: France
facility: Research Site
city: Bad Reichenhall
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Bonn
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Würzburg
country: Germany
facility: Research Site
city: Ashkelon
country: Israel
facility: Research Site
city: Ramat Gan
country: Israel
facility: Research Site
city: Firenze
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Padova
country: Italy
facility: Research Site
city: Pisa
country: Italy
facility: Research Site
city: San Giovanni Rotondo
country: Italy
facility: Research Site
city: Verona
country: Italy
facility: Research Site
city: Hiroshima-shi
country: Japan
facility: Research Site
city: Iizuka-shi
country: Japan
facility: Research Site
city: Osaka
country: Japan
facility: Research Site
city: Sapporo-shi
country: Japan
facility: Research Site
city: Yaizu-shi
country: Japan
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Suwon-si
country: Korea, Republic of
facility: Research Site
city: Łódź
country: Poland
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Granada
country: Spain
facility: Research Site
city: La Laguna
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Santander
country: Spain
facility: Research Site
city: Vitoria
country: Spain
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan
country: Taiwan
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Erzurum
country: Turkey
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
Study officials:
References: