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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%.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1: MK-8723 1 mg/kg in Healthy Participants | Experimental | 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 | Experimental | 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 | Experimental | 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 | Experimental | 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 | Experimental | MK-8723 100 mg/kg administered as a single IV infusion to healthy participants in Part 1. |
|
| Part 1: Matching Placebo to MK-8723 |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MK-8723 | Drug | MK-8723 administered as a single IV infusion over approximately 4 hours on Day 1. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Up to 84 days |
| Number of Participants Discontinuing Study Due to an Adverse Event (AE) | 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 | 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 |
| 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 | 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 |
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Inclusion Criteria (Part 1):
Inclusion Criteria (Part 2):
Exclusion Criteria (Part 1):
Exclusion Criteria (Part 2):
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
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2 participants that completed Part 2 10 mg/kg were re-enrolled in Part 2 100 mg/kg & dosed. Both participants completed Part 2 100 mg/kg. 1 participant originally assigned to Part 2 30 mg/kg received placebo in error & is included in Part 2 Placebo.
Amendment 3 specified a re-enrollment procedure for eligible participants in Part 2 to participate in more than one dosing panel.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| FG002 | 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. |
| FG003 | 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. |
| FG004 | 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. |
| FG005 | Part 1: Matching Placebo to MK-8723 | Matching placebo to MK-8723 administered as a single IV infusion to healthy participants in Part 1. |
| FG006 | Part 2: MK-8723 10 mg/kg in ITP Participants | MK-8723 10 mg/kg administered as a single IV infusion to participants with immune thrombocytopenia purpura (ITP) in Part 2. 2 participants were subsequently enrolled in Part 2 MK-8723 100 mg/kg. |
| FG007 | 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. |
| FG008 | 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. 2 participants with ITP from Part 2 MK-8723 10 mg/kg were re-enrolled into Part 2 100 mg/kg and dosed (not shown). |
| FG009 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Baseline characteristics are presented for all participants that enrolled in the study according to the actual treatment administered (i.e., as treated). 2 participants that completed Part 2 MK-8723 10 mg/kg were re-enrolled in Part 2 MK-8723 100 mg/kg and dosed per protocol procedure.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | Part 1: MK-8723 3 mg/kg in Healthy Participants |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | The All Participants as Treated (APaT) population consisting of all participants who received at least one dose of study drug was used for the safety analysis. | Posted | Number | Participants | Up to 84 days |
|
Up to 84 days
The APaT population consisting of all participants who received at least one dose of study drug was used for the safety analysis. AEs are presented according to the actual treatment administered (i.e., as treated). 2 participants that completed Part 2 MK-8723 10 mg/kg were re-enrolled in Part 2 MK-8723 100 mg/kg & dosed per protocol procedure.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal distension | Gastrointestinal disorders | MedDRA version 18.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
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| Placebo Comparator |
Matching placebo to MK-8723 administered as a single IV infusion to healthy participants in Part 1. |
|
| Part 2: MK-8723 10 mg/kg in ITP Participants | Experimental | MK-8723 10 mg/kg administered as a single IV infusion to participants with ITP in Part 2. |
|
| Part 2: MK-8723 30 mg/kg in ITP Participants | Experimental | MK-8723 30 mg/kg administered as a single IV infusion to participants with ITP in Part 2. |
|
| Part 2: MK-8723 100 mg/kg in ITP Participants | Placebo Comparator | 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 | Placebo Comparator | Matching placebo to MK-8723 administered as a single IV infusion to participants with ITP in Part 2. |
|
| Matching Placebo | Drug | Matching placebo to MK-8723 administered as a single IV infusion over approximately 4 hours on Day 1. |
|
| 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. | 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 |
MK-8723 3 mg/kg administered as a single IV infusion to healthy participants in Part 1.
| BG002 | 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. |
| BG003 | 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. |
| BG004 | 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. |
| BG005 | Part 1: Matching Placebo to MK-8723 | Matching placebo to MK-8723 administered as a single IV infusion to healthy participants in Part 1. |
| BG006 | 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. 2 participants subsequently enrolled in Part 2 MK-8723 100 mg/kg. |
| BG007 | 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. |
| BG008 | 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. This group includes 2 participants that re-enrolled from Part 2 MK-8723 10 mg/kg. |
| BG009 | 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. |
| BG010 | Total | Total of all reporting groups |
| Years |
|
| Age, Customized | Number | Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
MK-8723 3 mg/kg administered as a single IV infusion to healthy participants in Part 1. |
| OG002 | 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. |
| OG003 | 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. |
| OG004 | 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. |
| OG005 | Part 1: Matching Placebo to MK-8723 | Matching placebo to MK-8723 administered as a single IV infusion to healthy participants in Part 1. |
| OG006 | 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. 2 participants subsequently enrolled in Part 2 MK-8723 100 mg/kg. |
| OG007 | 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. |
| OG008 | 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. This group includes 2 participants that re-enrolled from Part 2 MK-8723 10 mg/kg. |
| OG009 | 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. |
|
|
| Primary | Number of Participants Discontinuing Study Due to an Adverse Event (AE) | 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. | The APaT population consisting of all participants who received at least one dose of study drug was used for the safety analysis. | Posted | Number | Participants | Up to 84 Days |
|
|
|
| Primary | 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. | The per protocol population consisting of all participants in compliance with the protocol (e.g., availability of measurements, absence of major protocol violations) was used for the pharmacodynamic (platelet response) analysis. | Posted | Number | Participants | Up to Day 14 |
|
|
|
| Secondary | 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. | The per protocol population consisting of all participants in compliance with the protocol (e.g., availability of measurements, absence of major protocol violations) was used for the pharmacokinetic (AUC0-∞) analysis. | Posted | Geometric Mean | Geometric Coefficient of Variation | hr*μg/mL | 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 |
|
|
|
| Secondary | 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. | The per protocol population consisting of all participants in compliance with the protocol (e.g., availability of measurements, absence of major protocol violations) was used for this pharmacokinetic (Cmax) analysis. | Posted | Geometric Mean | Geometric Coefficient of Variation | μg/mL | 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 |
|
|
|
| 0 |
| 6 |
| 2 |
| 6 |
| EG001 | 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. | 0 | 6 | 2 | 6 |
| EG002 | 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. | 0 | 6 | 4 | 6 |
| EG003 | 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. | 0 | 6 | 1 | 6 |
| EG004 | 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. | 0 | 6 | 4 | 6 |
| EG005 | Part 1: Matching Placebo to MK-8723 | Matching placebo to MK-8723 administered as a single IV infusion to healthy participants in Part 1. | 0 | 10 | 6 | 10 |
| EG006 | 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. 2 participants subsequently enrolled in Part 2 MK-8723 100 mg/kg. | 0 | 3 | 1 | 3 |
| EG007 | 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. | 0 | 2 | 2 | 2 |
| EG008 | 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. This group includes 2 participants that re-enrolled from Part 2 MK-8723 10 mg/kg. | 0 | 3 | 2 | 3 |
| EG009 | 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. | 0 | 4 | 2 | 4 |
| Diarrhoea | Gastrointestinal disorders | MedDRA version 18.0 | Systematic Assessment |
|
| Frequent bowel movements | Gastrointestinal disorders | MedDRA version 18.0 | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA version 18.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA version 18.0 | Systematic Assessment |
|
| Feeling abnormal | General disorders | MedDRA version 18.0 | Systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA version 18.0 | Systematic Assessment |
|
| Infectious mononucleosis | Infections and infestations | MedDRA version 18.0 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA version 18.0 | Systematic Assessment |
|
| Wrist fracture | Injury, poisoning and procedural complications | MedDRA version 18.0 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA version 18.0 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA version 18.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA version 18.0 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA version 18.0 | Systematic Assessment |
|
| Myalgia intercostal | Musculoskeletal and connective tissue disorders | MedDRA version 18.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA version 18.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA version 18.0 | Systematic Assessment |
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| Lethargy | Nervous system disorders | MedDRA version 18.0 | Systematic Assessment |
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| Presyncope | Nervous system disorders | MedDRA version 18.0 | Systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA version 18.0 | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA version 18.0 | Systematic Assessment |
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| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA version 18.0 | Systematic Assessment |
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| Blood blister | Skin and subcutaneous tissue disorders | MedDRA version 18.0 | Systematic Assessment |
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| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA version 18.0 | Systematic Assessment |
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| Swelling face | Skin and subcutaneous tissue disorders | MedDRA version 18.0 | Systematic Assessment |
|
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results.