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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
48

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • United States
    • Florida
      • Miami, Florida, United States, 33014
        • Clinical Pharmacology of Miami

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Must be considered healthy. Healthy status is defined by absence of evidence of any active or chronic disease
  2. 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.
  3. 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.
  4. Hemoglobin ≥12.0g/ld.

Exclusion Criteria:

  1. Have a history of allergic reaction to C1 INH products (e.g. C1 Inhibitor [Human], Berinert [C1 Estrace Inhibitor (Human)] and C1 estrace [recombinant]
  2. Known history of alcohol or other substance abuse within the last year.
  3. Donation of blood or blood products within 60 days prior to receiving investigational product.
  4. 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.
  5. 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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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).
Drug: Recombinant human C1 esterase inhibitor
Subjects will receive escalating doses I-IV as both IV and SC injections
Other Names:
  • SHP623
Drug: SHP623
SHP623
Placebo Comparator: Placebo
3 Subjects will receive placebo for each cohort
Drug: Placebo
Placebo
Drug: Placebo
Subjects will receive matching placebo

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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)
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.
From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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).
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.
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.
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).
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.
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.
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).
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.
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.
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)].
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.
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.
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)].
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.
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.
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)].
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.
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.
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)].
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Shire

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 19, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 5, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 5, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 21, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 21, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 26, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 3, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 13, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • SHP623-100

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