pilot trial of single dose ilofotase alfa in hypophosphatasia

Conditions: Hypophosphatasia

Summary: the goal of this clinical trial is to compare the effectiveness of two doses of ilofotase alfa, an enzyme replacement treatment, in patients with hypophosphatasia (hpp). the main question it aims to answer is if the harmful accumulating levels of extracellular inorganic pyrophosphate (ppi) and pyridoxal 5'-phosphate (plp) can be reduced with ilofotase alfa. researchers will compare the two doses of ilofotase alfa to see if treatment effects differ between the doses.

recombinant human alkaline phosphatase (ilofotase alfa) is a full-length human chimeric alkaline phosphatase (alp) that could benefit patients with hypophosphatasia (hpp), which is characterized by low activity of tissue-nonspecific isoenzyme of alkaline phosphatase (tnsalp). this is a pilot trial for a potential future trial aimed at identifying whether treatment with ilofotase alfa can normalize circulating levels of ppi, plp and other biochemical markers of tnsalp deficiency along with the safety/tolerability of different doses of ilofotase alfa. the trial is designed as a single-center, open-label, randomized, parallel group clinical trial in adult patients with hpp. two different dose levels (0.8 mg/kg and 3.2 mg/kg) of ilofotase alfa will be assessed. participants will receive a single dose of ilofotase alfa, administered as a 1-hour intravenous infusion on study day 1. participants will stay at the research center for a total of 12 days; from 2 days before study drug administration (run-in) to 10 days after treatment. an additional follow-up assessment is scheduled 14 days after administration of ilofotase alfa. blood and urine samples will be taken daily for drug concentration and laboratory measurements assessing safety and effectiveness of treatment. in addition physical examinations will be performed on day 1 and as needed afterwards.

Eligibility criteria:
inclusion criteria: * genetically confirmed variant in the tissue-nonspecific isozyme alkaline phosphatase (alpl)-gene. * clinical symptoms of hpp. * 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). * provision of signed and dated informed consent form (icf) in accordance with local regulations at screening. * patients must agree not to get pregnant/not to get their partner pregnant, during the trial. consequently, patients must agree to use adequate contraception as detailed in study protocol. exclusion criteria: * participant is unable or unwilling to participate in all scheduled visits and perform all protocol-mandated assessments. * has a known or suspected hypersensitivity to ilofotase alfa or any components of the formulation used. * body weight \ 120 kilogram. * 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. * nsaid use in the past 2 weeks. * use of corticosteroids in the past 4 weeks. * use of compounds intended to interfere with bone metabolism (e.g. denosumab, teriparatide, romosozumab, raloxifene) in the past 3 months. * use of bisphosphonates in the past 2 years. * participation in a drug trial within 60 days, or five times the half-life of the drug, whichever is longer, prior to administration of ilofotase alfa. * use of asfotase alfa in the previous 3 months. patients will not be withheld from approved asfotase alfa if medically indicated. * a patient who is currently pregnant or lactating. * use of supplements including vitamin b6.

Keywords: enzyme replacement therapy