Pilot trial of single dose ilofotase alfa in hypophosphatasia

2023-503186-35-00 Protocol AP-recAP-HPP-01-01 Human pharmacology (Phase I) - Other Ended

Start 3 May 2023 · End 12 Jul 2023 · Status Ended · 1 EU/EEA countries · 1 sites · Protocol AP-recAP-HPP-01-01

Overview

Sponsor-declared trial summary

Phase Human pharmacology (Phase I) - Other
Status Ended
Participants planned 12
Countries 1
Sites 1

Hypophosphatasia

The change in Inorganic Pyrophosphate (PPi), and Pyridoxal 5’-phosphate (PLP) levels after low, and high dose ilofotase alfa in adult hypophosphatasia (HPP) patients.

Key facts

Sponsor
AM-Pharma B.V.
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
Trial duration
3 May 2023 → 12 Jul 2023
Decision date (initial)
2023-05-02
Transition trial
No
Low-intervention
No
Rare-disease indication
Yes
Vulnerable population
No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacodynamic, Pharmacokinetic

The change in Inorganic Pyrophosphate (PPi), and Pyridoxal 5’-phosphate (PLP) levels after low, and high dose
ilofotase alfa in adult hypophosphatasia (HPP) patients.

Conditions and MedDRA coding

Hypophosphatasia

VersionLevelCodeTermSystem organ class
20.1 PT 10049933 Hypophosphatasia 100000004850

Regulatory references

Scientific advice from competent authorities
European Medicines Agency

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

  1. 18-85 years old, inclusive.
  2. Genetically confirmed variant in the tissue-nonspecific isozyme alkaline phosphatase (ALPL)-Gene.
  3. Clinical symptoms of HPP.
  4. Medical history with 1) at least two independent measures of Alkaline Phosphatase (ALP) below lower level of normal (LLN) and 2) at least one measurement of either PPi or PLP above upper level of normal (ULN).
  5. Provision of signed and dated informed consent form (ICF) in accordance with local regulations at screening.
  6. Patients must agree to use adequate double-barrier contraception when sexually active. This applies for the period between trial drug administration and 14 days thereafter.

Exclusion criteria 12

  1. Is unable or unwilling to participate in all scheduled visits and perform all protocol-mandated assessments.
  2. Has a known or suspected hypersensitivity to ilofotase alfa or any components of the formulation used.
  3. Body weight < 40 kilogram and > 120 kilogram.
  4. Patient has a history of clinically significant abnormalities or of any illness that, in the opinion of the trial investigator, might confound the results of the trial or pose an additional risk to the patient by their participation in the trial.
  5. NSAID use in the past 2 weeks.
  6. Use of corticosteroids in the past 4 weeks.
  7. Use of compounds intended to interfere with bone metabolism (e.g. Denosumab, Teriparatide, Romosozumab, Raloxifene) in the past 3 months.
  8. Use of bisphosphonates in the past 2 years.
  9. Participation in a drug trial within 60 days prior to administration of ilofotase alfa.
  10. Use of asfotase alfa in the previous 3 months.
  11. A patient who is currently pregnant or lactating.
  12. Use of supplements including Vitamin B6.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. The effect of a low or high dose of ilofotase alfa on the biochemical profile in adult HPP patients.

Investigational products

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

Test 1

Ilofotase alfa

PRD10151386 · Product

Active substance
Ilofotase Alfa
Pharmaceutical form
CONCENTRATE FOR SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS
Max daily dose
3.2 mg/kg milligram(s)/kilogram
Max total dose
3.2 mg/kg milligram(s)/kilogram
Max treatment duration
1 Day(s)
Authorisation status
Not Authorised
MA holder
AM-PHARMA B.V.
Paediatric formulation
No
Orphan designation
Yes
Orphan designation number
EU/3/14/1427

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AM-Pharma B.V.

Sponsor organisation
AM-Pharma B.V.
Address
Stadsplateau 6
City
Utrecht
Postcode
3521 AZ
Country
Netherlands

Scientific contact point

Organisation
AM-Pharma B.V.
Contact name
Juliane Bernholz

Public contact point

Organisation
AM-Pharma B.V.
Contact name
Juliane Bernholz

Locations

1 EU/EEA country · 1 investigational sites

By country

CountryMS statusPlanned subjectsSites
Germany Ended 12 1
Rest of world 0

Investigational sites

Germany

1 site · Ended
Universitatsklinikum Wurzburg AöR
Clinical Osteology and Clinical Trial Unit, Brettreichstrasse 11, Frauenland, Wuerzburg

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
Germany 2023-05-03 2023-07-12 2023-05-15 2023-06-26

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

TitleSubmission dateStatusType
Summary of Results AP-recAP-HPP-01-01
SUM-32656
2024-07-03T09:55:00 Submitted Summary of Results

Layperson summary Annex V

TitleSubmission dateStatusType
Lay Person Summary AP-recAP-HPP-01-01 2024-07-03T09:55:09 Submitted Laypersons Summary of Results

Documents 2 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Laypersons summary of results (for publication) Lay_persons summary_25JUNE2024_v1_0 1
Summary of results (for publication) CTIS_Synopsis_AP-recAP-HPP-01-01 _final_27Jun24 1

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2023-01-27 Germany Acceptable
2023-04-26
2023-05-02
2 NON SUBSTANTIAL MODIFICATION NSM-1 2023-05-09 Germany Acceptable
2023-04-26
2023-05-09