- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01963260
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
Completed
Conditions
Intervention / Treatment
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
Interventional
Enrollment (Actual)
50
Phase
- 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
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 |
Intervention / Treatment |
---|---|
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.
|
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.
|
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.
|
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.
|
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.
|
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.
|
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.
|
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.
|
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.
|
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.
|
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
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
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
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)
October 31, 2013
Primary Completion (Actual)
April 26, 2015
Study Completion (Actual)
April 26, 2015
Study Registration Dates
First Submitted
October 11, 2013
First Submitted That Met QC Criteria
October 11, 2013
First Posted (Estimate)
October 16, 2013
Study Record Updates
Last Update Posted (Actual)
March 15, 2019
Last Update Submitted That Met QC Criteria
February 28, 2019
Last Verified
February 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Immune System Diseases
- Autoimmune Diseases
- Hematologic Diseases
- Hemorrhage
- Hemorrhagic Disorders
- Blood Coagulation Disorders
- Skin Manifestations
- Blood Platelet Disorders
- Thrombotic Microangiopathies
- Purpura
- Purpura, Thrombocytopenic
- Purpura, Thrombocytopenic, Idiopathic
- Thrombocytopenia
Other Study ID 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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