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

NCT04948554 | Terminated Phase 1 FDA Drug

• 4 other identifiers: 2225-002A1334-02MK-2225-0022021-001004-15
• Study Type: interventional
• Target: 5
• Locations: 4 countries
• Sites: 16

Brief Summary

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.

Conditions

Systemic Sclerosis With and Without Interstitial Lung Disease

Keywords

Diffuse Systemic Sclerosis; Scleroderma; Systemic Sclerosis; Systemic Sclerosis-associated Interstitial Lung Disease

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• Area Under the Concentration-Time Curve (AUC0-tau) of MK-2225

  Up to 12 Weeks

• Serum Maximum Concentration (Cmax) of MK-2225

  Up to 12 Weeks

• Time to peak Serum Concentration (Tmax) of MK-2225

  Up to 12 Weeks

• Serum Apparent Terminal Half-Life (t1/2) of MK-2225

  Up to 12 Weeks

• Accumulation ratio of AUCtau (RAUC)

  Up to 12 Weeks

Study Arms (12)

Cohort 1: MK-2225

EXPERIMENTAL

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

Cohort 1: Placebo

PLACEBO COMPARATOR

Participants in Cohort 1 will receive placebo Q2W plus SOC for 12 weeks.

Biological: Placebo

Cohort 2: MK-2225

EXPERIMENTAL

Participants in Cohort 2 will receive MK-2225 at 0.5 mg/kg (or lower) Q2W plus SOC for 12 weeks.

Biological: MK-2225

Cohort 2: Placebo

PLACEBO COMPARATOR

Participants in Cohort 2 will receive placebo Q2W plus SOC for 12 weeks.

Biological: Placebo

Cohort 3: MK-2225

EXPERIMENTAL

Participants in Cohort 3 will receive MK-2225 at 1.0 mg/kg (or lower) Q2W plus SOC for 12 weeks.

Biological: MK-2225

Cohort 3: Placebo

PLACEBO COMPARATOR

Participants in Cohort 3 will receive placebo Q2W plus SOC for 12 weeks.

Biological: Placebo

Cohort 4: MK-2225

EXPERIMENTAL

Participants in Cohort 4 will receive MK-2225 at ≤2.0 mg/kg Q2W if needed plus SOC for 12 weeks.

Biological: MK-2225

Cohort 4: Placebo

PLACEBO COMPARATOR

Participants in Cohort 4 will receive placebo Q2W plus SOC for 12 weeks.

Biological: Placebo

Cohort 5: MK-2225

EXPERIMENTAL

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

Cohort 5: Placebo

PLACEBO COMPARATOR

Participants in Cohort 5 will receive (no more frequent than Q2W) placebo plus SOC for 12 weeks.

Biological: Placebo

Cohort 6: MK-2225

EXPERIMENTAL

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

Cohort 6: Placebo

PLACEBO COMPARATOR

Participants in Cohort 6 will receive (no more frequent than Q2W) placebo plus SOC for 12 weeks.

Biological: Placebo

Interventions

MK-2225 BIOLOGICAL

Administered Subcutaneously (SC)

Also known as: ACE-1334

Cohort 1: MK-2225; Cohort 2: MK-2225; Cohort 3: MK-2225; Cohort 4: MK-2225; Cohort 5: MK-2225; Cohort 6: MK-2225

Placebo BIOLOGICAL

Administered SC

Cohort 1: Placebo; Cohort 2: Placebo; Cohort 3: Placebo; Cohort 4: Placebo; Cohort 5: Placebo; Cohort 6: Placebo

Eligibility Criteria

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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA: lead

Study Sites (16)

UCSD Altman Clinical and Translational Research Institute (Site 1013)

La Jolla, California, 92037-0943, United States

Location

Keck Medical Center ( Site 1001)

Los Angeles, California, 90033, United States

Location

Georgetown University Medical Center ( Site 1010)

Washington D.C., District of Columbia, 20007, United States

Location

University of Florida ( Site 1002)

Gainesville, Florida, 32610, United States

Location

Central Florida Pulmonary Group ( Site 1005)

Orlando, Florida, 32803, United States

Location

Medster Research, LLC ( Site 1017)

Valdosta, Georgia, 31605-1096, United States

Location

University of Kansas Medical Center ( Site 1007)

Kansas City, Kansas, 66160, United States

Location

The Cleveland Clinic Foundation ( Site 1003)

Cleveland, Ohio, 44195, United States

Location

Penn State Milton S Hershey Medical Center ( Site 1004)

Hershey, Pennsylvania, 17033, United States

Location

West Tennessee Research Institute ( Site 1012)

Jackson, Tennessee, 38305, United States

Location

Metroplex Clinical Research Center ( Site 1018)

Dallas, Texas, 75231-4446, United States

Location

Mount Sinai Hospital ( Site 1101)

Toronto, Ontario, M5T 3L9, Canada

Location

Azienda Ospedaliero Universitaria Careggi (Site 1401)

Florence, Tuscany, 50134, Italy

Location

Azienda Ospedaliera Universitaria Integrata Di Verona ( Site 1402)

Verona, Veneto, 37134, Italy

Location

Kantonsspital St. Gallen (Site 1301)

Sankt Gallen, Canton of St. Gallen, 9000, Switzerland

Location

Hôpital Neuchatelois ( Site 1304)

Neuchâtel, Neuchâtel (fr), 2000, Switzerland

Location

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Scleroderma, Diffuse; Scleroderma, Systemic

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: June 4, 2021
• First Posted: July 2, 2021
• Study Start: March 10, 2023
• Primary Completion: October 18, 2023
• Study Completion: October 18, 2023
• Last Updated: November 24, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share

Locations

CA (1); US (11); CH (2); IT (2)