Microdose and First-In-Human (FIH) Study of Recombinant Human Placental Alkaline Phosphatase (hRESCAP)

NCT01889147 | Completed Early Phase 1 DMC

• 1 other identifier: CHDR1220
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

In the present study human recombinant placental alkaline phosphatase (hRESCAP) will be investigated. Alkaline Phosphatase is naturally present in the body and reported to use lipopolysaccharde (LPS, bacterial endotoxins) and extracellular nucleotides leaking from damaged and ischemic cells as physiological substrates. The LPS-substrate prevalence makes alkaline phosphatase an interesting novel therapeutic agent in the treatment of LPS-mediated diseases. A bovine homologue of this protein (bovine intestinal alkaline phosphatase, BIAP) has previously been investigated for treatment of acute inflammatory responses such as sepsis, and was shown to be safe in humans. hRESCAP, which will be investigated in the current study, is expected to have a longer half-life in humans than the previously investigated BIAP, due to the fact that it is more sialylated. The possibility to increase the t1/2 to days instead of minutes enables treatment of chronic diseases.

Conditions

Healthy

Keywords

Peak plasma concentration; safety and efficacy; therapeutic agent; LPS-mediated diseases; Pharmacokinetics of administered hRESCAP; Determine half-time

Outcome Measures

Primary Outcomes (1)

• Evaluate the peak plasma concentration of hRESCAP after microdose administration of hRESCAP

  After administration of hRESCAP intravenously, blood will be withdrawn of the subjects frequently for in total 35 days (five times the anticipated half-life period of one week).

  35 days

Secondary Outcomes (1)

• In the ascending dose study increased dosages of of hRESCAP will be supplied till finally the therapeutic dose.

  Two weeks (based upon time phrame of micodose section of the study)

Study Arms (3)

14C-hRESCAP

ACTIVE COMPARATOR

Peak plasma concentration response of a dose hRESCAP will be examined and compared with the saline condition

Biological: hRESCAP

saline

PLACEBO COMPARATOR

Peak plasma concentration response of different dosages of hRESCAP will be examined and controlled with the saline condition

Biological: Placebo

Microdose

ACTIVE COMPARATOR

Peak plasma concentration of a very low dose of hRESCAP as a first test in humans (first starting dose, before the other arms).

Biological: hRESCAP

Interventions

hRESCAP BIOLOGICAL

one acute bolus administration of different dosages of hRESCAP (microdose, part 1; and FIH: low dose, 414 µg; medium dose, 2480 µg; high dose, 5300 µg; part 2)

Also known as: recombinant human placental alkaline phosphatase

14C-hRESCAP; Microdose

Placebo BIOLOGICAL

saline

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male subjects, 18 - 45 years of age, inclusive. Healthy status is defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead ECG, haematology, blood chemistry, and urinalysis;
• Body mass index (BMI) between 18 and 30 kg/m2, inclusive;
• Ability to communicate well with the investigator in the Dutch language;
• Able to participate and willing to give written informed consent and to comply with the study restrictions;
• Venous access sufficient to allow blood sampling as per protocol.

You may not qualify if:

• Any clinically significant abnormality as determined by medical history taking and physical examinations obtained during the screening visit that in the opinion of the investigator would interfere with the study objectives or compromise subject safety;
• History of a surgical event that may significantly affect the study outcome;
• History of allergy or other inflammatory indications;
• History of asthma or other inflammatory disease;
• Use of prescription medications, over the counter medications, vitamin, herbal and dietary supplements within 21 days prior to study drug administrations, or less than 5 half-lives, whichever is longer, and during the course of the study.
• Alkaline Phosphatase levels in plasma of \< 30 IU/L or \> 115 IU/L;
• Clinically relevant abnormal laboratory results, ECG, vital signs, or physical findings at screening that in the opinion of the investigator would interfere with the study objectives or compromise subject safety;
• Participation in an investigational drug, food (ingredients) or device study within 3 months prior to screening or more than 4 times in the past year;
• Any psychological conditions which, in the opinion of the investigator, might create undue risk to the subject or interfere with the subject's ability to comply with the protocol;
• History of alcohol or illicit drug abuse (alcohol abuse defined as alcohol consumption \> 28 units/week);
• Reported unexplained weight loss or weight gain of \> 2 kg in the month prior to screening;
• Positive test results for Hepatitis B, Hepatitis C or HIV;
• Donation of blood within 3 months prior to screening or donation of plasma within 14 days prior to screening;
• Not having a general practitioner;
• Not willing to accept information transfer which concerns participation in the study, or information regarding health, like laboratory results, findings at anamnesis or physical examination and eventual adverse events to and from his general practitioner;

Sponsors & Collaborators

• TNO: lead
• Alloksys Life Sciences B.V.: collaborator

Study Sites (1)

Centre for Human Drug Research

Leiden, South Holland, 2333CL, Netherlands

Location

Study Officials

• Koos Burggraaf, MD, PhD

  CHDR

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Project Manager Clinical Studies Food and Pharma

Study Record Dates

• First Submitted: June 18, 2013
• First Posted: June 28, 2013
• Study Start: June 1, 2013
• Primary Completion: July 1, 2013
• Study Completion: October 1, 2013
• Last Updated: October 24, 2013

Record last verified: 2013-10

Locations

NL (1)