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

Primary Purpose

Immune Thrombocytopenia Purpura

Status

Completed

Phase

Phase 1

Locations

Study Type

Interventional

Intervention

MK-8723

Matching Placebo

About this trial

This is an interventional treatment trial for Immune Thrombocytopenia Purpura

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

Part 1: MK-8723 1 mg/kg in Healthy Participants

Part 1: MK-8723 3 mg/kg in Healthy Participants

Part 1: MK-8723 10 mg/kg in Healthy Participants

Part 1: MK-8723 30 mg/kg in Healthy Participants

Part 1: MK-8723 100 mg/kg in Healthy Participants

Part 1: Matching Placebo to MK-8723

Part 2: MK-8723 10 mg/kg in ITP Participants

Part 2: MK-8723 30 mg/kg in ITP Participants

Part 2: MK-8723 100 mg/kg in ITP Participants

Part 2: Matching Placebo to MK-8723

Arm Description

MK-8723 1 mg/kg administered as a single IV infusion to healthy participants in Part 1.

MK-8723 3 mg/kg administered as a single IV infusion to healthy participants in Part 1.

MK-8723 10 mg/kg administered as a single IV infusion to healthy participants in Part 1.

MK-8723 30 mg/kg administered as a single IV infusion to healthy participants in Part 1.

MK-8723 100 mg/kg administered as a single IV infusion to healthy participants in Part 1.

Matching placebo to MK-8723 administered as a single IV infusion to healthy participants in Part 1.

MK-8723 10 mg/kg administered as a single IV infusion to participants with ITP in Part 2.

MK-8723 30 mg/kg administered as a single IV infusion to participants with ITP in Part 2.

MK-8723 100 mg/kg administered as a single IV infusion to participants with ITP in Part 2.

Matching placebo to MK-8723 administered as a single IV infusion to participants with ITP in Part 2.

Outcomes

Primary Outcome Measures

Number of Participants Experiencing an Adverse Event

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.

Number of Participants Discontinuing Study Due to an Adverse Event (AE)

Number of Participants With a Positive Platelet Response to MK-8723

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.

Secondary Outcome Measures

Area Under the Concentration-time Curve of MK-8723 From Time 0 to Infinity (AUC0-∞) Among Healthy Participants and Participants With ITP

AUC0-∞ is a measure of total body exposure to drug. Serum samples for determination of AUC0-∞ were collected at pre-specified time-points.

Maximum Concentration (Cmax) of MK-8723 Among Healthy Participants and Participants With ITP

Serum samples for determination of Cmax were collected at pre-specified time-points.

Full Information

NCT ID

NCT01963260

First Posted

October 11, 2013

Last Updated

February 28, 2019

Sponsor

Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT01963260

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2019

Overall Recruitment Status

Completed

Study Start Date

October 31, 2013 (Actual)

Primary Completion Date

April 26, 2015 (Actual)

Study Completion Date

April 26, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Merck Sharp & Dohme LLC

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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%.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Immune Thrombocytopenia Purpura

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

50 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part 1: MK-8723 1 mg/kg in Healthy Participants

Arm Type

Experimental

Arm Description

MK-8723 1 mg/kg administered as a single IV infusion to healthy participants in Part 1.

Arm Title

Part 1: MK-8723 3 mg/kg in Healthy Participants

Arm Type

Experimental

Arm Description

MK-8723 3 mg/kg administered as a single IV infusion to healthy participants in Part 1.

Arm Title

Part 1: MK-8723 10 mg/kg in Healthy Participants

Arm Type

Experimental

Arm Description

MK-8723 10 mg/kg administered as a single IV infusion to healthy participants in Part 1.

Arm Title

Part 1: MK-8723 30 mg/kg in Healthy Participants

Arm Type

Experimental

Arm Description

MK-8723 30 mg/kg administered as a single IV infusion to healthy participants in Part 1.

Arm Title

Part 1: MK-8723 100 mg/kg in Healthy Participants

Arm Type

Experimental

Arm Description

MK-8723 100 mg/kg administered as a single IV infusion to healthy participants in Part 1.

Arm Title

Part 1: Matching Placebo to MK-8723

Arm Type

Placebo Comparator

Arm Description

Matching placebo to MK-8723 administered as a single IV infusion to healthy participants in Part 1.

Arm Title

Part 2: MK-8723 10 mg/kg in ITP Participants

Arm Type

Experimental

Arm Description

MK-8723 10 mg/kg administered as a single IV infusion to participants with ITP in Part 2.

Arm Title

Part 2: MK-8723 30 mg/kg in ITP Participants

Arm Type

Experimental

Arm Description

MK-8723 30 mg/kg administered as a single IV infusion to participants with ITP in Part 2.

Arm Title

Part 2: MK-8723 100 mg/kg in ITP Participants

Arm Type

Placebo Comparator

Arm Description

MK-8723 100 mg/kg administered as a single IV infusion to participants with ITP in Part 2.

Arm Title

Part 2: Matching Placebo to MK-8723

Arm Type

Placebo Comparator

Arm Description

Matching placebo to MK-8723 administered as a single IV infusion to participants with ITP in Part 2.

Intervention Type

Drug

Intervention Name(s)

MK-8723

Intervention Description

MK-8723 administered as a single IV infusion over approximately 4 hours on Day 1.

Intervention Type

Drug

Intervention Name(s)

Matching Placebo

Intervention Description

Matching placebo to MK-8723 administered as a single IV infusion over approximately 4 hours on Day 1.

Primary Outcome Measure Information:

Title

Number of Participants Experiencing an Adverse Event

Description

Time Frame

Up to 84 days

Title

Number of Participants Discontinuing Study Due to an Adverse Event (AE)

Description

Time Frame

Up to 84 Days

Title

Number of Participants With a Positive Platelet Response to MK-8723

Description

Time Frame

Up to Day 14

Secondary Outcome Measure Information:

Title

Area Under the Concentration-time Curve of MK-8723 From Time 0 to Infinity (AUC0-∞) Among Healthy Participants and Participants With ITP

Description

AUC0-∞ is a measure of total body exposure to drug. Serum samples for determination of AUC0-∞ were collected at pre-specified time-points.

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

Title

Maximum Concentration (Cmax) of MK-8723 Among Healthy Participants and Participants With ITP

Description

Serum samples for determination of Cmax were collected at pre-specified time-points.

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Director

Organizational Affiliation

Merck Sharp & Dohme LLC

Official's Role

Study Director

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

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

IPD Sharing URL

http://engagezone.msd.com/ds_documentation.php

Learn more about this trial

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

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