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

NCT ID: NCT01963260

Last Updated: 2019-03-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-31
• Study Completion Date: 2015-04-26

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.

Conditions

Immune Thrombocytopenia Purpura

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

MK-8723

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

MK-8723

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

MK-8723

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

MK-8723

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

MK-8723

Intervention Type: DRUG

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

Part 1: Matching Placebo to MK-8723

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

Group Type: PLACEBO_COMPARATOR

Matching Placebo

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

MK-8723

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

MK-8723

Intervention Type: DRUG

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

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.

Group Type: PLACEBO_COMPARATOR

MK-8723

Intervention Type: DRUG

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

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.

Group Type: PLACEBO_COMPARATOR

Matching Placebo

Intervention Type: DRUG

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

Interventions

MK-8723

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

Intervention Type: DRUG

Matching Placebo

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

• 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

• 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

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Other Identifiers

8723-001

Identifier Type: -

Identifier Source: org_study_id