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

Immune Thrombocytopenia Purpura Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01963260
• Other study ID #: 8723-001
• Status: Completed
• Phase: Phase 1
• Start date: October 31, 2013
• Est. completion date: April 26, 2015

Study information

• Verified date: February 2019
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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%.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: April 26, 2015
• Est. primary completion date: April 26, 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Immune Thrombocytopenia Purpura
• Purpura
• Purpura, Thrombocytopenic
• Purpura, Thrombocytopenic, Idiopathic
• Thrombocytopenia

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Up to 84 days
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.	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.	Up to Day 14
Secondary	Area Under the Concentration-time Curve of MK-8723 From Time 0 to Infinity (AUC0-8) Among Healthy Participants and Participants With ITP	AUC0-8 is a measure of total body exposure to drug. Serum samples for determination of AUC0-8 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
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.	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