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

Phase 1

Completed

• Conditions: Immune Thrombocytopenia Purpura
• Interventions: Drug: MK-8723; Drug: Matching Placebo

• Registration Number: NCT01963260
• Lead Sponsor: Merck Sharp & Dohme LLC

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.

Study Timeline

• Study First Submitted: 2013-10-11
• Study First Submitted QC: 2013-10-11
• Study First Posted: 2013-10-16
• Study Start: 2013-10-31
• Primary Completion: 2015-04-26
• Study Completion: 2015-04-26
• Results First Submitted: 2017-01-31
• Results First Submitted QC: 2017-01-31
• Results First Posted: 2017-03-21
• Status Verified: 2019-02
• Last Update Submitted: 2019-02-28
• Last Update Posted: 2019-03-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part 1: MK-8723 1 mg/kg in Healthy Participants	MK-8723	MK-8723 1 mg/kg administered as a single IV infusion to healthy participants in Part 1.
Part 1: MK-8723 3 mg/kg in Healthy Participants	MK-8723	MK-8723 3 mg/kg administered as a single IV infusion to healthy participants in Part 1.
Part 1: MK-8723 10 mg/kg in Healthy Participants	MK-8723	MK-8723 10 mg/kg administered as a single IV infusion to healthy participants in Part 1.
Part 1: MK-8723 30 mg/kg in Healthy Participants	MK-8723	MK-8723 30 mg/kg administered as a single IV infusion to healthy participants in Part 1.
Part 1: MK-8723 100 mg/kg in Healthy Participants	MK-8723	MK-8723 100 mg/kg administered as a single IV infusion to healthy participants in Part 1.
Part 1: Matching Placebo to MK-8723	Matching Placebo	Matching placebo to MK-8723 administered as a single IV infusion to healthy participants in Part 1.
Part 2: MK-8723 100 mg/kg in ITP Participants	MK-8723	MK-8723 100 mg/kg administered as a single IV infusion to participants with ITP in Part 2.
Part 2: Matching Placebo to MK-8723	Matching Placebo	Matching placebo to MK-8723 administered as a single IV infusion to participants with ITP in Part 2.
Part 2: MK-8723 30 mg/kg in ITP Participants	MK-8723	MK-8723 30 mg/kg administered as a single IV infusion to participants with ITP in Part 2.
Part 2: MK-8723 10 mg/kg in ITP Participants	MK-8723	MK-8723 10 mg/kg administered as a single IV infusion to participants with ITP in Part 2.

Primary Outcome Measures

Name	Time	Method
Number of Participants Experiencing an Adverse Event	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.
Number of Participants Discontinuing Study Due to an Adverse Event (AE)	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.
Number of Participants With a Positive Platelet Response to MK-8723	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.

Secondary Outcome Measures

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