Phase 3 Study of ALXN1850 in Pediatric Participants with HPP Previously Treated with Asfotase Alfa

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Alexion Pharmaceuticals Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Decision date (initial)

2024-04-17

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacokinetic, Pharmacodynamic

To assess the safety and tolerability of ALXN1850 versus asfotase alfa in pediatric participants with HPP previously treated with asfotase alfa

Secondary objectives 6

1. To evaluate the efficacy of ALXN1850 versus asfotase alfa on radiographic outcomes in pediatric participants with HPP previously treated with asfotase alfa
2. To assess the efficacy of ALXN1850 versus asfotase alfa on functional outcomes in pediatric participants with HPP previously treated with asfotase alfa
3. To evaluate the effect of treatment with ALXN1850 versus asfotase alfa on fatigue, pain, and health related quality of life outcomes in pediatric participants with HPP previously treated with asfotase alfa
4. To assess treatment satisfaction with ALXN1850 versus asfotase in pediatric participants with HPP previously treated with asfotase alfa
5. To assess the PK and PD of treatment with ALXN1850 versus asfotase alfa in pediatric participants with HPP previously treated with asfotase alfa
6. To assess the immunogenicity to ALXN1850 and asfotase alfa in pediatric participants with HPP previously treated with asfotase alfa

Conditions and MedDRA coding

Hypophosphatasia

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

Pharmaceuticals And Medical Devices Agency, Food And Drug Administration

EMA paediatric investigation plan (PIP)

EMEA-003343-PIP01-22

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Participant must be ≥ 2 and < 12 years of age at Day 1.
2. Diagnosis of HPP documented in the medical records.
3. Presence of open growth plates by X-ray during Screening Period.
4. Tanner stage 2 or less during the Screening Period.
5. Must have been treated with 6 mg/kg/week of asfotase alfa via SC injection administered as either 2 mg/kg 3 times per week or 1 mg/kg 6 times per week for ≥ 6 months before Day 1.
6. Female participants of childbearing potential and male participants must follow contraception requirements and guidance as defined in the protocol.
7. 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 this protocol.

Exclusion criteria 25

1. 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.
2. Diagnosis of primary or secondary hyperparathyroidism.
3. Hypoparathyroidism, unless secondary to HPP.
4. Any new fracture within 12 weeks before Day 1 (excluding pseudofractures).
5. Planned surgical intervention which may impact the results of study assessments (in the opinion of the Investigator) during the Randomized Evaluation Period.
6. History of allergy or hypersensitivity to any ingredient contained in asfotase alfa or ALXN1850.
7. Body weight < 10 kg during the Screening Period.
8. Received vitamin B6 (including vitamin supplements that contain vitamin B6) within 6 weeks before Day 1.
9. Received oral bisphosphonate within 6 months before Day 1.
10. Received IV bisphosphonate within 12 months before Day 1.
11. Received a parathyroid hormone (PTH)-related protein analog (eg, abaloparatide) or PTH analog (eg, teriparatide) within 2 weeks before Day 1.
12. Received strontium within 6 months before Day 1.
13. Received sclerostin inhibitors within 6 months before Day 1.
14. Received growth hormone therapy within 6 months before Day 1.
15. Received estrogen agonist/antagonist/inhibitor within 2 months before Day 1 unless used as contraception or for treatment of dysmenorrhea.
16. Received a RANKL inhibitor within 6 months before Day 1.
17. 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.
18. Corrected calcium levels (adjusted for albumin) below age-adjusted normal range during Screening.
19. Serum phosphorus levels below the age-adjusted normal range during Screening.
20. Evidence of a treatable form of rickets (eg, vitamin D deficiency) other than HPP during Screening.
21. Serum 25-hydroxy (25-OH) vitamin D below 20 ng/mL during Screening.
22. PTH > upper limit of normal (ULN) of the laboratory reference range during Screening.
23. Participants who are unwilling to undergo genetic testing for the ALPL gene.
24. Participants who are pregnant, planning to become pregnant, or breastfeeding during the course of the study.
25. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence of TEAEs, TESAEs, AESIs and AEs leading to study intervention discontinuation or interruption

Secondary endpoints 11

1. RGI-C score at the end of the Randomized Evaluation Period (Day 169)
2. Change from baseline in RSS at the end of the Randomized Evaluation Period (Day 169)
3. Change from baseline in 6MWT at the end of the Randomized Evaluation Period (Day 169) (≥ 5 years of age)
4. Change from baseline in % Predicted 6MWT at the end of the Randomized Evaluation Period (Day 169) (≥ 5 years of age)
5. Change from baseline in BOT-2 at the end of the Randomized Evaluation Period (Day 169) (≥ 4 years of age)
6. Change from baseline in PDMS-3 at the end of the Randomized Evaluation Period (Day 169) (< 4 years of age)
7. Change from baseline at the end of the Randomized Evaluation Period (Day 169) in the following:- EQ-5D-Y health state score (≥ 8 years of age)- EQ-5D-Y-Proxy Version 1 health state score (≥ 4 to < 8 years of age)- PODCI Self-Report global function score (≥ 11 years of age)- PODCI-Parent global function score (< 11 years of age)- APPT score (≥ 8 years of age)- Pediatric FACIT-Fatigue score (≥ 8 years of age)- Pediatric FACIT-Fatigue Proxy score (≥ 2 to < 8 years of age)
8. TSQM-9 score at the end of the Randomized Evaluation Period (Day 169)
9. Plasma ALXN1850 and asfotase alfa concentration or activity at predose or trough (Ctrough) over time through the end of the Randomized Evaluation Period (Day 169)
10. Plasma PPi, PLP, PA, and PLP/PL concentration or ratio and change from baseline over time through the end of the Randomized Evaluation Period (Day 169)
11. ADA incidence, ADA response categories, and ADA titer, as well as NAb incidence and NAb titers in participants treated with ALXN1850 or asfotase alfa, as appropriate.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Alexion Pharmaceuticals Inc.

Sponsor organisation

Alexion Pharmaceuticals Inc.

Address

121 Seaport Boulevard

City

Boston

Postcode

02210-2050

Country

United States

Scientific contact point

Organisation

Alexion Pharmaceuticals Inc.

Contact name

European Clinical Trial Information

Public contact point

Organisation

Alexion Pharmaceuticals Inc.

Contact name

European Clinical Trial Information

Locations

3 EU/EEA countries · 7 investigational sites

By country

Investigational sites

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Application history

1 submissions — initial application plus substantial / non-substantial modifications