- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02663687
Phase 1 Study to Assess the Safety, Tolerability, and Pharmacokinetics of Recombinant Human C1 Esterase Inhibitor in Healthy Adult Subjects
May 13, 2021 updated by: Shire
A Randomized, Double-blind, Placebo-controlled, Ascending Dose, Phase 1 Study to Assess the Safety, Tolerability, and Pharmacokinetics of Single Intravenous and Subcutaneous Doses of Recombinant Human C1 Esterase Inhibitor in Healthy Adult Subjects
This trial is looking to gain information about the safety and tolerability of an investigational treatment (SHP623) in healthy adult volunteers.
This study will also collect pharmacokinetic data (how the body absorbs and breaks down the study drug).
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
48
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Florida
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Miami, Florida, United States, 33014
- Clinical Pharmacology of Miami
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 50 years (Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Must be considered healthy. Healthy status is defined by absence of evidence of any active or chronic disease
- Male, or non-pregnant, non-lactating female, who agrees to comply with any applicable contraceptive requirements of the protocol, or females of non-child-bearing potential.
- Body mass index between 18.0 and 30.0 kg/m2 inclusive with a body weight >50 kg (110 lbs.). This inclusion criterion will be assessed only at the first screening visit.
- Hemoglobin ≥12.0g/ld.
Exclusion Criteria:
- Have a history of allergic reaction to C1 INH products (e.g. C1 Inhibitor [Human], Berinert [C1 Estrace Inhibitor (Human)] and C1 estrace [recombinant]
- Known history of alcohol or other substance abuse within the last year.
- Donation of blood or blood products within 60 days prior to receiving investigational product.
- Current use of any medication except hormonal replacement therapy, hormonal contraceptives and occasional use of any over-the-counter non-steroidal anti-inflammatory drug (NSAID) or acetaminophen.
- Have a history of hypercoagulability or other predisposition to thrombotic events.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment 1- 4
Treatment A: 9 Subjects will receive dose level I of SHP623 intravenously (IV).
B: 9 Subjects will receive dose level I of SHP623 subcutaneously(SC).
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Subjects will receive escalating doses I-IV as both IV and SC injections
Other Names:
SHP623
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Placebo Comparator: Placebo
3 Subjects will receive placebo for each cohort
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Placebo
Subjects will receive matching placebo
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Treatment-emergent Adverse Events (TEAEs ) Including Serious Adverse Events (SAEs)
Time Frame: From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
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An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that did not necessarily have a causal relationship with this treatment.
An AE was considered to be a TEAE in a specific treatment period of the study if the date and time of onset were after investigational product administration in that period and if it occurred less than equals to (<=) Day 28 and was both not present at the start of that period and was not a chronic condition that was part of the participant's medical history, or it was present at the start of that period or as part of the participant's medical history but the severity or frequency increased during that period <= Day 28.
An SAE was defined as any untoward medical occurrence (whether considered to be related to investigational product or not) that at any dose.
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From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Observed Plasma Concentration (Cmax) of SHP623 Occurring at Time of Maximum Observed Concentration During a Dosing Interval (Tmax)
Time Frame: Pre-dose, 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216, 312, 648 hours post-dose.
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Cmax of SHP623 recombinant human C1 esterase inhibitor (rC1 INH) antigen at Tmax was calculated based on observed concentration-versus-time data.
Cmax at Tmax of SHP623 for both treatment period 1 (IV) and treatment period 2 (SC) was presented in the categories for each dosing group.
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Pre-dose, 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216, 312, 648 hours post-dose.
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Time of Maximum Plasma Concentration (Tmax) of SHP623 Sampled During a Dosing Interval
Time Frame: Pre-dose, 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216, 312, 648 hours post-dose.
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Tmax of SHP623 (rC1 INH) antigen was calculated based on observed concentration-versus-time data.
Tmax of SHP623 for both treatment period 1 (IV) and treatment period 2 (SC) was presented in the categories for each dosing group.
|
Pre-dose, 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216, 312, 648 hours post-dose.
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Terminal Half-life (t1/2) of SHP623
Time Frame: Pre-dose, 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216, 312, 648 hours post-dose.
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t1/2 is the time required for the concentration of the drug to reach half of its original value.
t1/2 of SHP623 (rC1 INH) antigen for both treatment period 1 (IV) and treatment period 2 (SC) was presented in the categories for each dosing group.
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Pre-dose, 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216, 312, 648 hours post-dose.
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Area Under the Plasma Concentration Curve From Time Zero to Infinity (AUC 0-inf) of SHP623
Time Frame: Pre-dose, 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216, 312, 648 hours post-dose.
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AUC 0-inf is the area under the curve extrapolated to infinity, calculated using the observed value of the last non-zero concentration.
AUC 0-inf of SHP623 (rC1 INH) antigen was calculated from observed concentration-versus-time data.
AUC 0-inf of SHP623 for both treatment period 1 (IV) and treatment period 2 (SC) was presented in the categories for each dosing group.
The unit of measure is hour*microgram per milliliter (hr*mcg/ml).
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Pre-dose, 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216, 312, 648 hours post-dose.
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Area Under the Plasma Concentration Curve From Time Zero to 168 Hours Postdose (AUC 0-168) of SHP623
Time Frame: Pre-dose, 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216, 312, 648 hours post-dose.
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AUC 0-168 is the area under the concentration curve over the interval from 0 to 168 hours after dosing of SHP623.
AUC 0-168 of SHP623 (rC1 INH) was calculated based on observed concentration-versus-time data.
AUC 0-168 of SHP623 for both treatment period 1 (IV) and treatment period 2 (SC) was presented in the categories for each dosing group.
The unit of measure is hour*microgram per milliliter (hr*mcg/ml).
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Pre-dose, 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216, 312, 648 hours post-dose.
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Area Under the Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of SHP623
Time Frame: Pre-dose, 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216, 312, 648 hours post-dose.
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AUClast is the area under the curve from the time 0 to the last measurable concentration of SHP623 (rC1 INH), which was calculated from observed concentration-versus-time data.
AUClast of SHP623 for both treatment period 1 (IV) and treatment period 2 (SC) was presented in the categories for each dosing group.
The unit of measure is hour*microgram per milliliter (hr*mcg/ml).
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Pre-dose, 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216, 312, 648 hours post-dose.
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Total Body Clearance (CL) for Intravascular (IV) Administration of SHP623
Time Frame: Pre-dose, 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216, 312, 648 hours post-dose.
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CL is the total body clearance of SHP623 for IV administration.
The unit of measurement is unit per hour*microgram per milliliter [U/(hr*mcg/ml)].
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Pre-dose, 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216, 312, 648 hours post-dose.
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Volume of Distribution Associated With the Terminal Slope (Vz) Following Intravenous (IV) Administration of SHP623
Time Frame: Pre-dose, 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216, 312, 648 hours post-dose.
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Vz is the volume of distribution associated with the terminal slope following IV administration.
Vz was calculated for SHP 623 (rC1 INH) antigen from observed concentration-versus-time data.
The unit of measure is unit per microgram per milliliter [U/(mcg/ml)].
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Pre-dose, 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216, 312, 648 hours post-dose.
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Total Body Clearance for Extravascular Administration (CL/F) of SHP623 for Subcutaneous (SC) Administration
Time Frame: Pre-dose, 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216, 312, 648 hours post-dose.
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CL/F is the total body clearance for extravascular administration of SHP623 for SC administration divided by the fraction of dose absorbed.
CL/F of SHP623 (rC1 INH) was calculated based on observed concentration-versus-time data.
The unit of measure is unit per hour*microgram per milliliter [U/(hr*mcg/ml)].
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Pre-dose, 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216, 312, 648 hours post-dose.
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Volume of Distribution Influenced by Fraction of Dose Absorbed (Vz/F) Following Extravascular Administration of SHP623
Time Frame: Pre-dose, 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216, 312, 648 hours post-dose.
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Vz/F is the volume of distribution associated with the terminal slope following extravascular administration divided by the fraction of dose absorbed for subcutaneous (SC) administration.
Vz/F of SHP623 (rC1 INH) were calculated from observed concentration-versus-time data.
The unit of measure is unit per microgram per milliliter [U/(mcg/ml)].
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Pre-dose, 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216, 312, 648 hours post-dose.
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
February 19, 2016
Primary Completion (Actual)
December 5, 2016
Study Completion (Actual)
December 5, 2016
Study Registration Dates
First Submitted
December 21, 2015
First Submitted That Met QC Criteria
January 21, 2016
First Posted (Estimate)
January 26, 2016
Study Record Updates
Last Update Posted (Actual)
June 3, 2021
Last Update Submitted That Met QC Criteria
May 13, 2021
Last Verified
May 1, 2021
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Skin Diseases
- Immunologic Deficiency Syndromes
- Immune System Diseases
- Hypersensitivity, Immediate
- Genetic Diseases, Inborn
- Skin Diseases, Vascular
- Hypersensitivity
- Urticaria
- Hereditary Complement Deficiency Diseases
- Primary Immunodeficiency Diseases
- Angioedema
- Angioedemas, Hereditary
- Physiological Effects of Drugs
- Immunosuppressive Agents
- Immunologic Factors
- Complement Inactivating Agents
- Complement C1 Inhibitor Protein
- Complement C1 Inactivator Proteins
- Complement C1s
Other Study ID Numbers
- SHP623-100
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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