Safety and Pharmacokinetics of MK-2060 in Older Participants With End-Stage Renal Disease on Hemodialysis (MK-2060-004)

NCT03873038 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 2060-004MK-2060-004
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of MK-2060 after intravenous (IV) administration of single and multiple doses in older adult participants with end-stage renal disease (ESRD) on hemodialysis (HD).

Conditions

Renal Dialysis; Kidney Failure, Chronic

Outcome Measures

Primary Outcomes (10)

• Part 1: Percentage of Participants With Any Adverse Event (AE)

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants that experienced an AE was summarized.

  Up to 164 days

• Part 2: Percentage of Participants With Any AE

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who experienced an AE was summarized.

  Up to 118 days

• Part 1: Percentage of Participants With Any Serious Adverse Event

  A serious adverse event (SAE) is an AE that results in death, is life threatening, requires or prolongs an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is another important medical event deemed such by medical or scientific judgment. The percentage of participants who experienced an SAE was summarized.

  Up to 164 days

• Part 2: Percentage of Participants With Any SAE

  An SAE is an AE that results in death, is life threatening, requires or prolongs an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is another important medical event deemed such by medical or scientific judgment. The percentage of participants who experienced an SAE was summarized.

  Up to 118 days

• Part 1: Percentage of Participants With a Systemic AE

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The solicited systemic AEs assessed included but not limited to fever, vital sign (VS) changes (tachycardia/hypotension), pruritis, urticarial (hives), lip swelling, angioedema, bronchospasm, stridor, hoarseness, and shortness of breath.

  Up to 164 days

• Part 2: Percentage of Participants With a Systemic AE

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The solicited systemic AEs assessed included but not limited to fever, vital sign (VS) changes (tachycardia/hypotension), pruritis, urticarial (hives), lip swelling, angioedema, bronchospasm, stridor, hoarseness, and shortness of breath.

  Up to 118 days

• Part 1: Percentage of Participants With an Injection-Site AE

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The solicited injection-site AEs assessed were pain, tenderness, erythema/redness, and induration/swelling.

  Up to 164 days

• Part 2: Percentage of Participants With an Injection-Site AE

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The solicited injection-site AEs assessed were pain, tenderness, erythema/redness, and induration/swelling.

  Up to 118 days

• Part 1: Percentage of Participants Discontinuing the Study Due to an AE

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants that discontinued the study due to an AE was summarized.

  Up to 164 days

• Part 2: Percentage of Participants Discontinuing Study Drug Due to an AE

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants that had study drug discontinued regardless of study completion status was summarized.

  Up to 4 weeks

Secondary Outcomes (14)

• Part 1: Area Under the Plasma Concentration-Time Curve of MK-2060 From 0 to Infinity (AUC0-inf)

  Predose Day 1 and 1, 12, 24, 48, 52, 96, 168 hours postdose, then Days 12, 15, 22, 29, 60, 90, 120, 150

• Part 1: Area Under the Plasma Concentration-Time Curve of MK-2060 From Time 0 to 168 Hours (AUC0-168)

  Predose Day 1 and 1, 12, 24, 48, 52, 96, 168 hours postdose

• Part 1: Maximum Observed Plasma Concentration (Cmax) of MK-2060

  Predose Day 1 and 1, 12, 24, 48, 52, 96, 168 hours postdose, then Days 12, 15, 22, 29, 60, 90, 120, 150

• Part 1: Plasma Concentration of MK-2060 at 168 Hours (C168)

  168 hours post dose

• Part 1: Time to Maximum Observed Plasma Drug Concentration (Tmax) of MK-2060

  Predose Day 1 and 1, 12, 24, 48, 52, 96, 168 hours postdose

Study Arms (6)

Part 1: Panel A- MK-2060 (8 mg)

EXPERIMENTAL

Participants will receive a single 8-mg dose of MK-2060 via intravenous (IV) infusion.

Drug: MK-2060

Part 1: Panel B- MK-2060 (20 mg)

EXPERIMENTAL

Participants will receive a single 20-mg dose of MK-2060 via IV infusion.

Drug: MK-2060

Part 1: Panel C- MK-2060 (40 mg)

EXPERIMENTAL

Participants will receive a single 40-mg dose of MK-2060 via IV infusion.

Drug: MK-2060

Part 1: Placebo

PLACEBO COMPARATOR

Participants will receive a single dose of placebo via IV infusion.

Drug: Placebo

Part 2: MK-2060 25-mg Loading/ 25-mg Maintenance

EXPERIMENTAL

Participants will receive three doses of up to 25 mg MK-2060 via IV infusion in the first week (Week 1), followed by a single dose of up to 25 mg MK-2060 via IV infusion weekly for 3 weeks (Weeks 2-4)

Drug: MK-2060

Part 2: Placebo

PLACEBO COMPARATOR

Participants will receive three doses of placebo via IV infusion in the first week and then a single dose of placebo via IV infusion weekly for 3 weeks (Weeks 2-4)

Drug: Placebo

Interventions

MK-2060 DRUG

Part 1: Single doses (8 mg, 20 mg, or 40 mg) of MK-2060 will be administered via IV infusion on Day 1. Part 2: Three doses of 25 mg of MK- 2060 administered via IV infusion on Days 1, 3 and 5; Followed by single doses of 25 mg of MK-2060 administered via IV infusion on Days 8, 15, and 22.

Part 1: Panel A- MK-2060 (8 mg); Part 1: Panel B- MK-2060 (20 mg); Part 1: Panel C- MK-2060 (40 mg); Part 2: MK-2060 25-mg Loading/ 25-mg Maintenance

Placebo DRUG

Part 1: Single dose of placebo will be administered via IV infusion on Day 1. Part 2: Three doses of placebo administered via IV infusion on Days 1, 3 and 5; Followed by single doses of placebo administered via IV infusion on Days 8, 15, and 22.

Part 1: Placebo; Part 2: Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, of non-child bearing potential (WONCBP) age ≥40 and ≤80 years for Part 1 and ≥18 and ≤80 years for Part 2.
• End-stage renal disease (ESRD) maintained on stable outpatient hemodialysis (HD) regimen, using an established (\> 3 months) and normally functioning, regular flow, uninfected mature arteriovenous (AV) fistula or AV graft and skin consistent with standard chronic HD access injuries, and HD stability defined as (\[K, dialyzer clearance, multiplied by t, time, divided by V, patient's total body water\] Kt/V) ≥ 1.2 within 3 months prior to dosing at a healthcare center for \> 3 months from dosing.
• On HD regimen at least 3 times per week for a minimum of 3 hours per dialysis session, using a complication-free well-maintained AV fistula or AV graft, expected and plan to continue this throughout and for at least 3 months beyond the study.
• Has a Body Mass Index (BMI) ≥ 18 and ≤ 45 kg/m\^2, BMI = weight (kg)/height (m)\^2.
• Baseline health is judged to be stable based on medical history, physical examination, vital sign measurements and electrocardiogram (ECG) performed prior to randomization.
• Liver function test (serum alanine aminotransferase \[ALT\] and aspartate aminotransferase \[AST\]) must be equal to or below 1.5X upper limit of normal (ULN) and deemed not clinically significant by both the investigator and the Sponsor.
• Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies by agreeing to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant. Also, men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile-vaginal penetration.
• Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies in that a female participant is eligible to participate if she is not pregnant or breastfeeding and she is not a WOCBP in that she is a postmenopausal female without menses for at least 1 year OR is a surgically sterile female, post hysterectomy, bilateral salpingectomy, oophorectomy or tubal ligation.

You may not qualify if:

• Has a history of any clinically significant concomitant disease or condition (including treatment for such conditions) or diseases whose current condition is considered clinically unstable that, in the opinion of the investigator, could either interfere with the study drug, compromise interpretation of study data, or pose an unacceptable risk. Participants with a remote history of uncomplicated medical events (e.g., uncomplicated kidney stones, as defined as spontaneous passage and no recurrence in the last 5 years, or childhood asthma) may be enrolled in the study at the discretion of the investigator.
• Is mentally or legally incapacitated, has significant emotional problems at the time of prestudy (screening) visit or expected during the conduct of the study or has a history of clinically significant psychiatric disorder of the last 5 years. Participants who have had situational depression may be enrolled in the study at the discretion of the investigator.
• Has a history of cancer (malignancy), including adenocarcinoma, with possible exceptions being participants with adequately treated non-melanomatous skin carcinoma; participants with other malignancies which have been successfully treated ≥10 years prior to the pretrial (screening) visit; or participants who, in the opinion of the trial investigator, are highly unlikely to sustain a recurrence for the duration of the trial.
• Has blood coagulation test (activated partial thromboplastin time \[aPTT\], prothrombin time \[PT\]) ≥ 20 % outside of normal range on pretrial (screening), which are considered clinically significant by both the investigator and the sponsor.
• Any other clinically significant abnormalities in laboratory test results at screening that would, in the opinion of the investigator, increase the participant's risk of participation, jeopardize complete participation in the study, or compromise interpretation of study data.
• Has a history of deep vein thrombosis or pulmonary embolism. Has a history of vascular access thrombosis within 1 month prior to enrollment. Has a personal or family history of bleeding disorder.
• Has a history of gastrointestinal (GI) bleeding, duodenal polyps or gastric ulcer in the last 5 years or severe hemorrhoidal bleed in last 3 months.
• Has a history of or current frequent epistaxis within the last 3 months or active gingivitis.
• Has ongoing anticoagulant therapy (warfarin, apixaban, dabigatran, rivaroxaban, edoxaban, betrixaban) or antiplatelet therapy (clopidogrel, prasugrel, ticagrelor, ticlopidine). Intradialytic heparin and aspirin are permitted.
• At the time of screening or pre-dose, has planned significant dental procedures (including planned dental surgery), or other planned surgical procedures within duration of participation in the trial.
• Is positive for hepatitis B surface antigen or human immunodeficiency viruses (HIV).
• Has had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the pre-study (screening) visits.
• Has a history of significant multiple and/or severe allergies (e.g. food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability (i.e. systemic allergic reaction) to prescription or non-prescription drugs or food.
• Has a tattoo, scar, or other physical finding at the area of the infusion site that would interfere with infusion or a local tolerability assessment.
• Has a history of receiving any human immunoglobulin preparation such as intravenous immunoglobulin (IVIG) or RhoGAM within the last year.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (3)

Orlando Clinical Research Center ( Site 0002)

Orlando, Florida, 32809, United States

Location

Prism Research ( Site 0003)

Saint Paul, Minnesota, 55114, United States

Location

New Orleans Center for Clinical Research ( Site 0001)

Knoxville, Tennessee, 37920, United States

Location

MeSH Terms

Conditions

Kidney Failure, Chronic

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2019
• First Posted: March 13, 2019
• Study Start: April 29, 2019
• Primary Completion: December 20, 2021
• Study Completion: December 20, 2021
• Last Updated: June 6, 2024
• Results First Posted: June 6, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share

Locations

US (3)