A Study of MK-2225 / ACE-1334 in Participants With Systemic Sclerosis With and Without Interstitial Lung Disease (MK-2225-002)

A Phase 1b Randomized, Double-Blind, Placebo-Controlled, Multiple-Ascending Dose Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of ACE-1334 Plus Standard of Care in Participants With Systemic Sclerosis

The purpose of the MK-2225-002 (A1334-02) study is to evaluate the safety and tolerability of MK-2225 (ACE-1334) plus standard of care (SOC) in participants with Systemic Sclerosis (SSc) following multiple doses.

Study Overview

• Status: Active, not recruiting
• Conditions: Systemic Sclerosis With and Without Interstitial Lung Disease
• Intervention / Treatment: Biological: MK-2225; Biological: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5T 3L9
      • Mount Sinai Hospital ( Site 1101)
• Italy
  • Tuscany
    • Florence, Tuscany, Italy, 50134
      • Azienda Ospedaliero Universitaria Careggi (Site 1401)
  • Veneto
    • Verona, Veneto, Italy, 37134
      • Azienda Ospedaliera Universitaria Integrata Di Verona ( Site 1402)
• Switzerland
  • Neuchâtel (fr)
    • Neuchâtel, Neuchâtel (fr), Switzerland, 2000
      • Hôpital Neuchatelois ( Site 1304)
  • Sankt Gallen
    • St Gallen, Sankt Gallen, Switzerland, 9000
      • Kantonsspital St. Gallen (Site 1301)
• United States
  • California
    • La Jolla, California, United States, 92037-0943
      • UCSD Altman Clinical and Translational Research Institute (Site 1013)
    • Los Angeles, California, United States, 90033
      • Keck Medical Center ( Site 1001)
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Medical Center ( Site 1010)
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida ( Site 1002)
    • Orlando, Florida, United States, 32803
      • Central Florida Pulmonary Group ( Site 1005)
  • Georgia
    • Valdosta, Georgia, United States, 31605-1096
      • Medster Research, LLC ( Site 1017)
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center ( Site 1007)
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation ( Site 1003)
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Milton S Hershey Medical Center ( Site 1004)
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • West Tennessee Research Institute ( Site 1012)
  • Texas
    • Dallas, Texas, United States, 75231-4446
      • Metroplex Clinical Research Center ( Site 1018)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

The main inclusion and exclusion criteria include but are not limited to the following:

Inclusion Criteria:

• Participants must have SSc, as defined using the 2013 American College of Rheumatology/European League Against Rheumatism criteria
• If participant is on a non-excluded immunosuppressive therapy (e.g. mycophenolate, methotrexate, azathioprine, etc.) the dose should be stable for > 2 months at the time of screening

• Women of childbearing potential must:

  • If sexually active, have used, and agree to use, highly effective contraception without interruption, for at least 28 days prior to starting investigational product, during the study (including dose interruptions), and for 17 weeks (119 days) after discontinuation of study treatment
  • Refrain from breastfeeding a child or donating blood, eggs, or ovum for the duration of the study and for at least 17 weeks (119 days) after the last dose of study treatment

• Male participants must:

  • Agree to use a condom, defined as a male latex condom or nonlatex condom NOT made out of natural (animal) membrane (e.g., polyurethane), during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions, and for at least 17 weeks (119 days) following investigational product discontinuation, even if he has undergone a successful vasectomy
  • Refrain from donating blood or sperm for the duration of the study and for 17 weeks (119 days) after the last dose of study treatment
• Must agree to not participate in any other study of investigational drugs/devices while enrolled in this study

Exclusion Criteria:

• Participant with SSc-pulmonary arterial hypertension (PAH) (except those participants with mild PAH on up to 2 oral drugs and mean pulmonary arterial pressure < 30 mmHg or low risk by risk calculator)
• In the opinion of the investigator, other clinically significant pulmonary abnormalities (such as obstructive lung disease, asthma, etc.)
• Other investigational therapy received within 1 month or 6 half-lives (whichever is greater) prior to the Screening Visit
• Prior exposure to MK-2225 or other TGF-β antibodies or any TGF-β family targeted biologic or hypersensitivity to the components of MK-2225
• Hypersensitivity to placebo or any of its components
• Previous hematopoietic stem cell transplantation (HSCT) or HSCT planned within the next year
• Major surgical procedures planned during the study period
• Oral prednisone or equivalent > 10 mg/day
• Participant with history of gastric antral vascular ectasia or gastrointestinal bleed
• On anticoagulation therapy (such as prophylaxis anticoagulation, warfarin, direct thrombin inhibitors or other including low molecular weight subcutaneous or intravenous therapeutic heparin), or antiplatelet therapy including aspirin. Use of fish oil supplements within 2 weeks prior to randomization and throughout study is not permitted.
• History of any other medical condition that might interfere with a participant's ability to participate in the study
• Active clinically significant viral, bacterial, or fungal infection, or any episode of infection requiring hospitalization within 4 weeks prior to screening
• Use of cyclophosphamide ≤ 6 months from screening
• Use of nintedanib or pirfenidone ≤ 28 days from screening
• Recent scleroderma renal crisis < 6 months before screening
• Use of tocilizumab ≤ 2 months from screening
• Has received any nonlive vaccine starting from 14 days prior to study intervention or is scheduled to receive any nonlive vaccine through 30 days following study intervention. Exception: COVID-19 vaccine may be administered.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

12

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: MK-2225; Participants in Cohort 1 will receive MK-2225 at 0.25 mg/kg once every two weeks (Q2W) plus standard of care (SOC) for 12 weeks.	Biological: MK-2225; Administered Subcutaneously (SC); Other Names: ACE-1334
Placebo Comparator: Cohort 1: Placebo; Participants in Cohort 1 will receive placebo Q2W plus SOC for 12 weeks.	Biological: Placebo; Administered SC
Experimental: Cohort 2: MK-2225; Participants in Cohort 2 will receive MK-2225 at 0.5 mg/kg (or lower) Q2W plus SOC for 12 weeks.	Biological: MK-2225; Administered Subcutaneously (SC); Other Names: ACE-1334
Placebo Comparator: Cohort 2: Placebo; Participants in Cohort 2 will receive placebo Q2W plus SOC for 12 weeks.	Biological: Placebo; Administered SC
Experimental: Cohort 3: MK-2225; Participants in Cohort 3 will receive MK-2225 at 1.0 mg/kg (or lower) Q2W plus SOC for 12 weeks.	Biological: MK-2225; Administered Subcutaneously (SC); Other Names: ACE-1334
Placebo Comparator: Cohort 3: Placebo; Participants in Cohort 3 will receive placebo Q2W plus SOC for 12 weeks.	Biological: Placebo; Administered SC
Experimental: Cohort 4: MK-2225; Participants in Cohort 4 will receive MK-2225 at ≤2.0 mg/kg Q2W if needed plus SOC for 12 weeks.	Biological: MK-2225; Administered Subcutaneously (SC); Other Names: ACE-1334
Placebo Comparator: Cohort 4: Placebo; Participants in Cohort 4 will receive placebo Q2W plus SOC for 12 weeks.	Biological: Placebo; Administered SC
Experimental: Cohort 5: MK-2225; Participants in Cohort 5 will receive MK-2225 (no more frequent than Q2W) ≤2.25 mg/kg Q2W or ≤4.5 mg/kg Q4W if needed plus SOC for 12 weeks.	Biological: MK-2225; Administered Subcutaneously (SC); Other Names: ACE-1334
Placebo Comparator: Cohort 5: Placebo; Participants in Cohort 5 will receive (no more frequent than Q2W) placebo plus SOC for 12 weeks.	Biological: Placebo; Administered SC
Experimental: Cohort 6: MK-2225; Participants in Cohort 6 will receive MK-2225 (no more frequent than Q2W) ≤2.25 mg/kg Q2W or ≤4.5 mg/kg Q4W if needed plus SOC for 12 weeks.	Biological: MK-2225; Administered Subcutaneously (SC); Other Names: ACE-1334
Placebo Comparator: Cohort 6: Placebo; Participants in Cohort 6 will receive (no more frequent than Q2W) placebo plus SOC for 12 weeks.	Biological: Placebo; Administered SC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with ≥1 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 number of participants who experienced an AE will be reported.	Up to 20 Weeks
Number of Participants Discontinuing from Study Therapy Due to 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 number of participants who discontinued study treatment due to an AE will be reported.	Up to 12 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration-Time Curve (AUC0-tau) of MK-2225	AUC0-tau is the area under the concentration-time curve. Blood samples will be collected at designated timepoints to determine AUC0-tau of MK-2225.	Up to 12 Weeks
Serum Maximum Concentration (Cmax) of MK-2225	Cmax is the maximum concentration of the drug observed in plasma. Blood samples will be collected at designated timepoints to determine Cmax of MK-2225.	Up to 12 Weeks
Time to peak Serum Concentration (Tmax) of MK-2225	Tmax is the amount of time required to reach Cmax. Blood samples will be collected at designated timepoints to determine Tmax of MK-2225.	Up to 12 Weeks
Serum Apparent Terminal Half-Life (t1/2) of MK-2225	t1/2 is the time required for 50% of drug to be cleared from serum. Blood samples will be collected at designated timepoints to determine t1/2 of MK-2225.	Up to 12 Weeks
Accumulation ratio of AUCtau (RAUC)	RAUC is the accumulation ratio of AUCtau after multiple doses relative to after a single dose. Blood samples will be collected at designated timepoints to determine RAUC of MK-2225.	Up to 12 Weeks

Collaborators and Investigators

• Sponsor: Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2023
• Primary Completion (Estimated): June 17, 2027
• Study Completion (Estimated): June 17, 2027

Study Registration Dates

• First Submitted: June 4, 2021
• First Submitted That Met QC Criteria: June 24, 2021
• First Posted (Actual): July 2, 2021

Study Record Updates

• Last Update Posted (Estimated): November 3, 2023
• Last Update Submitted That Met QC Criteria: November 2, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Systemic Sclerosis; Scleroderma; Diffuse Systemic Sclerosis; Systemic Sclerosis-associated Interstitial Lung Disease
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Respiratory Tract Diseases; Connective Tissue Diseases; Sclerosis; Lung Diseases; Scleroderma, Systemic; Scleroderma, Diffuse; Lung Diseases, Interstitial
• Other Study ID Numbers: 2225-002; A1334-02 (Other Identifier: Acceleronpharma); MK-2225-002 (Other Identifier: Merck); 2021-001004-15 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No