Single Rising Dose Study of MK-8723 in Healthy Participants and Participants With Immune Thrombocytopenia Purpura (MK-8723-001)

February 28, 2019 updated by: Merck Sharp & Dohme LLC

A Two-Part, Single Rising Dose Study to Assess the Safety, Pharmacokinetics and Pharmacodynamics of MK-8723 in Healthy Adults and Patients With Immune Thrombocytopenia Purpura

The primary objectives of this study are to assess the safety and tolerability of single rising doses of MK-8723 in healthy adult participants and adult participants with chronic immune thrombocytopenia purpura (ITP) and to assess pharmacodynamics of MK-8723 in participants with ITP. The primary hypothesis is that the true placebo-adjusted platelet response rate to MK-8723 in adult patients with chronic ITP is >50%.

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.

Detailed Description

In Part 1 of the trial, safety and pharmacokinetics of MK-8723 will be evaluated in healthy participants. In Part 2 of the trial, safety, pharmacokinetics, and pharmacodynamics will be evaluated among participants with ITP. In Part 1, dose escalation will occur in up to 5 serial panels of participants; each participant will receive a single intravenous (IV) dose of MK-8723 (or placebo). In Part 2, dose escalation will occur in up to 3 serial panels of participants with ITP; each participant will receive a single IV dose of MK-8723 (or placebo), once safety and tolerability of the corresponding dose is shown in Part 1. Amendment 3 specified a re-enrollment procedure for eligible participants in Part 2 to participate in more than one dosing panel.

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.
50

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

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 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria (Part 1):

  • Female participants must be non-pregnant, non-breast feeding, and of non-childbearing potential
  • Has a Body Mass Index (BMI) <=32 kg/m^2
  • Has a body weight >= 50 kg and <= 100 kg
  • Has been judged to be in good health based on medical history, physical examination, vital sign measurements, electrocardiogram (ECG), and laboratory safety tests
  • Non-smoker or has not used nicotine or nicotine-containing products for at least 3 months

Inclusion Criteria (Part 2):

  • Has been diagnosed with ITP at least 3 months prior
  • Female ITP participants must be non-pregnant, non-breast feeding, and either of 1) non-childbearing potential or 2) must have serum beta human chorionic gonadotropin (HCG) level consistent with a non-pregnant state, and agree to use acceptable contraception from pretrial period until 84 days postdose
  • Has a BMI <=36 kg/m^2
  • Has been judged to be in good health, other than ITP diagnosis, based on medical history, physical examination, vital sign measurements, ECG, and laboratory safety tests

Exclusion Criteria (Part 1):

  • Has a history or clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological abnormalities or diseases
  • Has a history of cancer (malignancy)
  • Has a history of significant multiple and/or severe allergies or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food
  • Is positive for hepatitis B surface antigen, hepatitis C antibodies, or human immunodeficiency virus (HIV)
  • Has had major surgery or donated or lost 1 unit of blood in the 4 weeks prior
  • Has participated in another investigational trial within 4 weeks (12 weeks for biologics)
  • Has received a live virus vaccination within 42 days or plans to receive such while participating in the trial
  • Is unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs and herbal remedies from 2 weeks prior and for the duration of the trial
  • Consumes greater than 3 glasses of alcoholic beverages per day
  • Consumes greater than 6 servings of caffeine-containing beverages per day
  • Is currently a regular user of any illicit drugs or has a history of drug and/or alcohol abuse within 3 months
  • Has a history of ITP or other autoimmune disease
  • Has an active infection that is clinically significant

Exclusion Criteria (Part 2):

  • Has a comorbid and significant hematological or immunological disorder
  • Has a history of significant multiple and/or severe allergies or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food
  • Is positive for hepatitis B surface antigen, hepatitis C antibodies, or HIV
  • Has had major surgery or donated or lost 1 unit of blood within 4 weeks
  • Has participated in another investigational trial within 4 weeks (12 weeks for biologics), excluding prior participation in the current study
  • Has a history of ITP unresponsive to intravenous immunoglobulin (IVIG)
  • Has had systemic corticosteroid use within 1 month (with the exception of stable low dose oral corticosteroids)
  • Has had systemic IVIG or other systemic immunomodulatory therapy, excluding MK-8723 administration in the current study, within 3 months
  • Has received a thrombopoietin receptor antagonist within 3 months
  • Is unable to refrain from using thrombopoietin receptor agonists and/or systemic immune modulatory medications throughout the study
  • Has received a live virus vaccine within 42 days prior or plans to receive such during the trial
  • Consumes greater than 3 alcoholic beverages per day
  • Consumes greater than 6 servings of caffeine-containing beverages per day
  • Is currently a regular user of any illicit drugs or has a history of drug and/or alcohol abuse within 3 months
  • Has clinical evidence of bleeding or coagulopathy including petechial rash, easy bruising, or excessive gingival bleeding with routine dental hygiene
  • Has an active infection that is clinically significant

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: Part 1: MK-8723 1 mg/kg in Healthy Participants
MK-8723 1 mg/kg administered as a single IV infusion to healthy participants in Part 1.
Drug: MK-8723
MK-8723 administered as a single IV infusion over approximately 4 hours on Day 1.
Experimental: Part 1: MK-8723 3 mg/kg in Healthy Participants
MK-8723 3 mg/kg administered as a single IV infusion to healthy participants in Part 1.
Drug: MK-8723
MK-8723 administered as a single IV infusion over approximately 4 hours on Day 1.
Experimental: Part 1: MK-8723 10 mg/kg in Healthy Participants
MK-8723 10 mg/kg administered as a single IV infusion to healthy participants in Part 1.
Drug: MK-8723
MK-8723 administered as a single IV infusion over approximately 4 hours on Day 1.
Experimental: Part 1: MK-8723 30 mg/kg in Healthy Participants
MK-8723 30 mg/kg administered as a single IV infusion to healthy participants in Part 1.
Drug: MK-8723
MK-8723 administered as a single IV infusion over approximately 4 hours on Day 1.
Experimental: Part 1: MK-8723 100 mg/kg in Healthy Participants
MK-8723 100 mg/kg administered as a single IV infusion to healthy participants in Part 1.
Drug: MK-8723
MK-8723 administered as a single IV infusion over approximately 4 hours on Day 1.
Placebo Comparator: Part 1: Matching Placebo to MK-8723
Matching placebo to MK-8723 administered as a single IV infusion to healthy participants in Part 1.
Drug: Matching Placebo
Matching placebo to MK-8723 administered as a single IV infusion over approximately 4 hours on Day 1.
Experimental: Part 2: MK-8723 10 mg/kg in ITP Participants
MK-8723 10 mg/kg administered as a single IV infusion to participants with ITP in Part 2.
Drug: MK-8723
MK-8723 administered as a single IV infusion over approximately 4 hours on Day 1.
Experimental: Part 2: MK-8723 30 mg/kg in ITP Participants
MK-8723 30 mg/kg administered as a single IV infusion to participants with ITP in Part 2.
Drug: MK-8723
MK-8723 administered as a single IV infusion over approximately 4 hours on Day 1.
Placebo Comparator: Part 2: MK-8723 100 mg/kg in ITP Participants
MK-8723 100 mg/kg administered as a single IV infusion to participants with ITP in Part 2.
Drug: MK-8723
MK-8723 administered as a single IV infusion over approximately 4 hours on Day 1.
Placebo Comparator: Part 2: Matching Placebo to MK-8723
Matching placebo to MK-8723 administered as a single IV infusion to participants with ITP in Part 2.
Drug: Matching Placebo
Matching placebo to MK-8723 administered as a single IV infusion over approximately 4 hours on Day 1.

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 Experiencing an Adverse Event
Time Frame: Up to 84 days
An AE is defined as any unfavorable and unintended medical occurrence in a clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Up to 84 days
Number of Participants Discontinuing Study Due to an Adverse Event (AE)
Time Frame: Up to 84 Days
An AE is defined as any unfavorable and unintended medical occurrence in a clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Up to 84 Days
Number of Participants With a Positive Platelet Response to MK-8723
Time Frame: Up to Day 14
In participants with ITP, platelet response is a rapid, sensitive, and highly qualitative measure of response to anti-inflammatory therapy. A positive platelet response was defined as: 1) A doubling of platelet counts at the time point of maximum response (through Day 14) as compared to Day 0 AND an increase to an absolute level of ≥50,000/μL in participants with a baseline platelet count of <50,000/μL, OR 2) A 50% increase in the platelet count at the time point of maximum response (through Day 14) as compared to Day 0 in participants with a baseline platelet count of ≥50,000/μL. The analysis was specified only for participants with ITP (Part 2) that received treatment with MK-8723 or matching placebo.
Up to Day 14

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
Area Under the Concentration-time Curve of MK-8723 From Time 0 to Infinity (AUC0-∞) Among Healthy Participants and Participants With ITP
Time Frame: All dose groups: Predose and 4 (end of infusion), 6, 12, 24 hrs postdose and Days 3, 4, 5, 7, 10, 14, 21, 28; 30 mg/kg and 100 mg/kg dose groups: Days 43, 56, 71, 84
AUC0-∞ is a measure of total body exposure to drug. Serum samples for determination of AUC0-∞ were collected at pre-specified time-points.
All dose groups: Predose and 4 (end of infusion), 6, 12, 24 hrs postdose and Days 3, 4, 5, 7, 10, 14, 21, 28; 30 mg/kg and 100 mg/kg dose groups: Days 43, 56, 71, 84
Maximum Concentration (Cmax) of MK-8723 Among Healthy Participants and Participants With ITP
Time Frame: All dose groups: Predose and 4 (end of infusion), 6, 12, 24 hrs postdose and Days 3, 4, 5, 7, 10, 14, 21, 28; 30 mg/kg and 100 mg/kg dose groups: Days 43, 56, 71, 84
Serum samples for determination of Cmax were collected at pre-specified time-points.
All dose groups: Predose and 4 (end of infusion), 6, 12, 24 hrs postdose and Days 3, 4, 5, 7, 10, 14, 21, 28; 30 mg/kg and 100 mg/kg dose groups: Days 43, 56, 71, 84

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.
Merck Sharp & Dohme LLC

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.
October 31, 2013

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.
April 26, 2015

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.
April 26, 2015

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).
October 11, 2013

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.
October 11, 2013

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.
October 16, 2013

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.
March 15, 2019

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.
February 28, 2019

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.
February 1, 2019

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.
  • 8723-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

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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