CHESTNUT: Phase 3 Study of ALXN1850 in Pediatric Participants With HPP Previously Treated With Asfotase Alfa

Sponsor

Alexion (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT06079372

Collaborator

(none)

Enrollment

Locations

Arms

45.5

Anticipated Duration (Months)

Patient Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary purpose of this study is to assess the safety and tolerability of ALXN1850 versus asfotase alfa in pediatric participants with HPP previously treated with asfotase alfa.

Condition or Disease	Intervention/Treatment	Phase
Hypophosphatasia	Drug: ALXN1850 Drug: asfotase alfa	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 3, Randomized, Open-label, Parallel-arm, Active-controlled, Multicenter Study to Evaluate Safety and Efficacy of ALXN1850 Versus Asfotase Alfa Administered Subcutaneously in Pediatric Participants (2 to < 12 Years of Age) With Hypophosphatasia (HPP) Previously Treated With Asfotase Alfa

Anticipated Study Start Date :

Nov 16, 2023

Anticipated Primary Completion Date :

Feb 18, 2025

Anticipated Study Completion Date :

Aug 31, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ALXN1850 Starting at Day 1 of the Randomized Evaluation Period participants will receive ALXN1850 for a total of 24 weeks. Participants will receive bodyweight dependent doses of either 20mg, 35mg or 50mg of ALXN1850 once q2w via SC injection. During Part A of the OLE Period, participants will have frequent visits over the first 24 weeks; Part B of the OLE Period participants will have visits every 9 months for up to approximately 108 weeks.	Drug: ALXN1850 ALXN1850 will be administered via subcutaneous (SC) injection. Drug: asfotase alfa Asfotase alfa will be administered via SC injection.
Experimental: asfotase alfa Starting at Day 1 of the Randomized Evaluation Period, participants will receive asfotase alfa for a total of 24 weeks. Participants will receive 6 mg/kg/week of asfotase alfa via SC injection as either 2 mg/kg 3 times per week or 1 mg/kg 6 times per week. Part A of the OLE Period participants will have frequent visits over the first 24 weeks; Part B will have visits every 9 months for up to approximately 108 weeks.	Drug: asfotase alfa Asfotase alfa will be administered via SC injection.

Arm

Intervention/Treatment

Experimental: ALXN1850

Starting at Day 1 of the Randomized Evaluation Period participants will receive ALXN1850 for a total of 24 weeks. Participants will receive bodyweight dependent doses of either 20mg, 35mg or 50mg of ALXN1850 once q2w via SC injection. During Part A of the OLE Period, participants will have frequent visits over the first 24 weeks; Part B of the OLE Period participants will have visits every 9 months for up to approximately 108 weeks.

Drug: ALXN1850

ALXN1850 will be administered via subcutaneous (SC) injection.

Drug: asfotase alfa

Asfotase alfa will be administered via SC injection.

Experimental: asfotase alfa

Starting at Day 1 of the Randomized Evaluation Period, participants will receive asfotase alfa for a total of 24 weeks. Participants will receive 6 mg/kg/week of asfotase alfa via SC injection as either 2 mg/kg 3 times per week or 1 mg/kg 6 times per week. Part A of the OLE Period participants will have frequent visits over the first 24 weeks; Part B will have visits every 9 months for up to approximately 108 weeks.

Drug: asfotase alfa

Asfotase alfa will be administered via SC injection.

Outcome Measures

Primary Outcome Measures

Number of Participants with Treatment-emergent Adverse Events (TEAEs) [Baseline Through Day 169]

Secondary Outcome Measures

Radiographic Global Impression of Change (RGI-C) Score at the end of the Randomized Evaluation Period (Day 169) [Baseline, Day 169]
Change from Baseline in Rickets Severity Score (RSS) at the end of the Randomized Evaluation Period (Day 169) [Baseline, Day 169]
Change from Baseline in 6-Minute Walk Test (6MWT) at the end of the Randomized Evaluation Period (Day 169) [Baseline, Day 169]
Change from Baseline in Percent Predicted 6MWT at the end of the Randomized Evaluation Period (Day 169) [Baseline, Day 169]
Change from Baseline in Bruininks Oseretsky Test of Motor Proficiency, Second Edition (BOT2) Score at the end of the Randomized Evaluation Period (Day 169) [Baseline, Day 169]
Change from Baseline in Peabody Developmental Motor Scales, Third Edition (PDMS-3) Score at the end of the Randomized Evaluation Period (Day 169) [Baseline, Day 169]

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years to 11 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosis of HPP documented in the medical records
Presence of open growth plates by X-ray during Screening Period
Tanner stage 2 or less during the Screening Period
Must have been treated with 6 mg/kg/ week of asfotase alfa via SC injection administered as either 2mg/kg 3 times per week or 1 mg/kg 6 times per week for ≥ 6 months before Day 1

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 asfotase alfa or ALXN1850
Body weight < 10 kg during the Screening Period

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Hartford	Connecticut	United States	06106
2	Research Site	Baltimore	Maryland	United States	21287
3	Research Site	Boston	Massachusetts	United States	02115
4	Research Site	Minneapolis	Minnesota	United States	55455
5	Research Site	Kansas City	Missouri	United States	64108
6	Research Site	Saint Louis	Missouri	United States	63110
7	Research Site	Durham	North Carolina	United States	27705
8	Research Site	Nashville	Tennessee	United States	37232
9	Research Site	Buenos Aires		Argentina	C1425BPE
10	Research Site	Córdoba		Argentina	5000
11	Research Site	Mar del Plata		Argentina	B7600FYK
12	Research Site	Mar del Plata		Argentina	B7600
13	Research Site	South Brisbane		Australia	4101
14	Research Site	Westmead		Australia	2145
15	Research Site	Winnepeg	Manitoba	Canada	R3E 3P4
16	Research Site	Ottawa	Ontario	Canada	K1H 8L1
17	Research Site	Le Kremlin Bicêtre		France	94270
18	Research Site	Paris		France	75015
19	Research Site	Homburg		Germany	66421
20	Research Site	Würzburg		Germany	97074
21	Research Site	Genova		Italy	16147
22	Research Site	Milano		Italy	20133
23	Research Site	Roma		Italy	00190
24	Research Site	Kyoto-shi		Japan	606-8507
25	Research Site	Minato-ku		Japan	105-8471
26	Research Site	Suita-shi		Japan	565-0871
27	Research Site	Istanbul		Turkey	34020
28	Research Site	Birmingham		United Kingdom	B4 6NH
29	Research Site	Manchester		United Kingdom
30	Research Site	Sheffield		United Kingdom	S10 2TH

Sponsors and Collaborators

Alexion

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Alexion

ClinicalTrials.gov Identifier:

NCT06079372

Other Study ID Numbers:

D8590C00004
ALXN1850-HPP-303

First Posted:

Oct 12, 2023

Last Update Posted:

Oct 12, 2023

Last Verified:

Oct 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Alexion

Additional relevant MeSH terms:

Hypophosphatasia

Study Results

No Results Posted as of Oct 12, 2023