HealthyEarly Phase 1NCT01889147

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

A Early Phase 1 study testing hRESCAP in people with Healthy, run by TNO at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 to 45 years, men onlyHealthy volunteers can take part
Conditions the study is for: Healthy
What is being tested?: hRESCAP
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 4 participants
Where: 1 siteNetherlands
Study dates: Jun 2013to Oct 2013
Phase: Early Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 45 years
Men only
Healthy volunteers accepted
Adult

Who may be able to join

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.

Who cannot join

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;

Show all 17Show fewer

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;
Not willing to give permission to have the general practitioner to be notified upon participation in this study;
Prior participation in part 1 is not allowed for subjects participating in part 2.

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

Centre for Human Drug Research
Leiden, South Holland, 2333CL

Other trials in Netherlands

About this study

Official title: A Single Dose Study to Assess the Peak Plasma Concentration of a Microdose of Recombinant Human Placental Alkaline Phosphatase (hRESCAP, Part 1) Followed by a Single Ascending Dose, FIH Study to Assess Safety and Tolerability of hRESCAP (Part 2).

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.

Read the detailed description

In the current study the peak plasma concentration (pharmacokinetics/elimination) of [14C]-labelled hRESCAP in healthy volunteers will be investigated at increasing single doses (up to anticipated therapeutic dose), with a microdose (≤30 nmol) as a safe starting dose.

Part 1: To assess the peak plasma concentration of a single microdose (≤30 nmol) of a recombinant human protein (hRESCAP), administered intravenously, as a suitable technique to predict the pharmacokinetics in humans at pharmacologically relevant doses;
Part 2: To determine the safety and tolerability of single dose of hRESCAP up to 5300 µg in healthy male volunteers administered intravenously;
To determine the peak plasma concentration of hRESCAP in healthy male volunteers within a pharmacologically relevant dose-range and compare this with BIAP pharmacokinetics with emphasis on half-life (t1/2).

Conditions: Healthy
Being tested: hRESCAP, Placebo
Keywords: Peak plasma concentration, safety and efficacy, therapeutic agent, LPS-mediated diseases, Pharmacokinetics of administered hRESCAP, Determine half-time

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

hRESCAPBiological
Also called recombinant human placental alkaline phosphatase
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)
PlaceboBiological

Study groups in NCT01889147
Study group	Role	What they receive
14C-hRESCAP	Active comparator	Peak plasma concentration response of a dose hRESCAP will be examined and compared with the saline condition Receives: Biological: hRESCAP
saline	Placebo comparator	Peak plasma concentration response of different dosages of hRESCAP will be examined and controlled with the saline condition Receives: 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). Receives: Biological: hRESCAP

What is being measured

The primary outcome is the main question the study is designed to answer.

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).
Measured: 35 days

Secondary outcomes (1)

In the ascending dose study increased dosages of of hRESCAP will be supplied till finally the therapeutic dose.
In three subjects a low, medium and high dose of hRESCAP will be administered and a control saline administration in one subject. The peak plasma concentration of hRESCAP response of different dosages will be useful for treatment evaluation. The administration of the different dosages supplied is one week apart for safety reasons.
Measured: Two weeks (based upon time phrame of micodose section of the study)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2013Oct 2013

First posted28 Jun 2013 (estimated)
Study startJun 2013
Primary completionJul 2013
Study completionOct 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for HealthyStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Early Phase 1
Primary purpose: Diagnosis
Allocation: Randomised
Intervention model: Single group
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 4 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01889147
Sponsor's protocol ID: CHDR1220
Status last verified: Oct 2013
First submitted: 18 Jun 2013
Last updated: 24 Oct 2013
Results posted: No
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Recruiting
THE EFFECTS OF GAME-BASED EXERCISE PROGRAMS
Physical Activity, Body Image
Not yet recruitingPhase 1
A Phase I Study of GLR2053 Tablets in Chinese Healthy Adult Participants
Atopic Dermatitis
Recruiting
Colon-delivered Riboflavin and Gut Microbiota Composition
Microbiome Dysbiosis, Gut Health
Not yet recruiting
Neuroergonomic Analysis of a Brain-Computer Interface Device (BCI)
Healthy Volunteers - Male and Female
RecruitingPhase 1
First-in-Human Trial to Assess REGN20423 in Healthy Adult Participants and Adult Participants With Atopic Dermatitis
Healthy Volunteer, Atopic Dermatitis

All Healthy trials

Study at a glance

From the registry record, last updated by the sponsor on 24 Oct 2013. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Single Dose Study to Assess the Peak Plasma Concentration of a Microdose of Recombinant Human Placental Alkaline Phosphatase (hRESCAP, Part 1) Followed by a Single Ascending Dose, FIH Study to Assess Safety and Tolerability of hRESCAP (Part 2).
ClinicalTrials.gov ID: NCT01889147
Acronym / sponsor ID: CHDR1220
Conditions: Healthy
Keywords: Peak plasma concentration, safety and efficacy, therapeutic agent, LPS-mediated diseases, Pharmacokinetics of administered hRESCAP, Determine half-time
Phase: Early Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 4 participants (estimated)
Lead sponsor: TNOUniversity, hospital or other
Collaborators: Alloksys Life Sciences B.V.
Study start: Jun 2013
Primary completion: Jul 2013 (actual)
Study completion: Oct 2013 (actual)
First posted: 28 Jun 2013 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Part 1: To assess the peak plasma concentration of a single microdose (≤30 nmol) of a recombinant human protein (hRESCAP), administered intravenously, as a suitable technique to predict the pharmacokinetics in humans at pharmacologically relevant doses;
Part 2: To determine the safety and tolerability of single dose of hRESCAP up to 5300 µg in healthy male volunteers administered intravenously;
To determine the peak plasma concentration of hRESCAP in healthy male volunteers within a pharmacologically relevant dose-range and compare this with BIAP pharmacokinetics with emphasis on half-life (t1/2).

Study design

Primary purpose: Diagnosis
Allocation: Randomised
Intervention model: Single group
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
14C-hRESCAP	Active comparator	Biological: hRESCAPPeak plasma concentration response of a dose hRESCAP will be examined and compared with the saline condition
saline	Placebo comparator	Biological: PlaceboPeak plasma concentration response of different dosages of hRESCAP will be examined and controlled with the saline condition
Microdose	Active comparator	Biological: hRESCAPPeak plasma concentration of a very low dose of hRESCAP as a first test in humans (first starting dose, before the other arms).

Who may qualify

Ages: 18 to 45 years
Sex: Male only
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (5 listed)

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.

Key exclusion criteria (17 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
hRESCAPAlso: recombinant human placental alkaline phosphataseone 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)	Biological	14C-hRESCAP, Microdose
Placebo	Biological	saline

Primary outcome

Evaluate the peak plasma concentration of hRESCAP after microdose administration of hRESCAP
Time frame: 35 days
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).

1 secondary outcome

In the ascending dose study increased dosages of of hRESCAP will be supplied till finally the therapeutic dose.
Time frame: Two weeks (based upon time phrame of micodose section of the study)

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Oct 2013.

Related trials for Healthy

Recruiting
THE EFFECTS OF GAME-BASED EXERCISE PROGRAMS
Physical Activity, Body Image
Not yet recruitingPhase 1
A Phase I Study of GLR2053 Tablets in Chinese Healthy Adult Participants
Atopic Dermatitis
Recruiting
Colon-delivered Riboflavin and Gut Microbiota Composition
Microbiome Dysbiosis, Gut Health
Not yet recruiting
Neuroergonomic Analysis of a Brain-Computer Interface Device (BCI)
Healthy Volunteers - Male and Female
RecruitingPhase 1
First-in-Human Trial to Assess REGN20423 in Healthy Adult Participants and Adult Participants With Atopic Dermatitis
Healthy Volunteer, Atopic Dermatitis

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Koos Burggraaf, MD, PhD principal investigator

CHDR

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing hRESCAP in people with Healthy, run by TNO at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Oct 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Evaluate the peak plasma concentration of hRESCAP after microdose administration of hRESCAP (time frame: 35 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01889147.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Oct 2013.