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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Systemic Sclerosis With and Without Interstitial Lung Disease

Intervention / Treatment
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* Biological: MK-2225
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: MK-2225<br>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<br>* Administered Subcutaneously (SC)<br>* Other names: ACE-1334;|
| Placebo Comparator: Cohort 1: Placebo<br>Participants in Cohort 1 will receive placebo Q2W plus SOC for 12 weeks. | Biological: Placebo<br>* Administered SC<br>|
| Experimental: Cohort 2: MK-2225<br>Participants in Cohort 2 will receive MK-2225 at 0.5 mg/kg (or lower) Q2W plus SOC for 12 weeks. | Biological: MK-2225<br>* Administered Subcutaneously (SC)<br>* Other names: ACE-1334;|
| Placebo Comparator: Cohort 2: Placebo<br>Participants in Cohort 2 will receive placebo Q2W plus SOC for 12 weeks. | Biological: Placebo<br>* Administered SC<br>|
| Experimental: Cohort 3: MK-2225<br>Participants in Cohort 3 will receive MK-2225 at 1.0 mg/kg (or lower) Q2W plus SOC for 12 weeks. | Biological: MK-2225<br>* Administered Subcutaneously (SC)<br>* Other names: ACE-1334;|
| Placebo Comparator: Cohort 3: Placebo<br>Participants in Cohort 3 will receive placebo Q2W plus SOC for 12 weeks. | Biological: Placebo<br>* Administered SC<br>|
| Experimental: Cohort 4: MK-2225<br>Participants in Cohort 4 will receive MK-2225 at ≤2.0 mg/kg Q2W if needed plus SOC for 12 weeks. | Biological: MK-2225<br>* Administered Subcutaneously (SC)<br>* Other names: ACE-1334;|
| Placebo Comparator: Cohort 4: Placebo<br>Participants in Cohort 4 will receive placebo Q2W plus SOC for 12 weeks. | Biological: Placebo<br>* Administered SC<br>|
| Experimental: Cohort 5: MK-2225<br>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<br>* Administered Subcutaneously (SC)<br>* Other names: ACE-1334;|
| Placebo Comparator: Cohort 5: Placebo<br>Participants in Cohort 5 will receive (no more frequent than Q2W) placebo plus SOC for 12 weeks. | Biological: Placebo<br>* Administered SC<br>|
| Experimental: Cohort 6: MK-2225<br>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<br>* Administered Subcutaneously (SC)<br>* Other names: ACE-1334;|
| Placebo Comparator: Cohort 6: Placebo<br>Participants in Cohort 6 will receive (no more frequent than Q2W) placebo plus SOC for 12 weeks. | Biological: Placebo<br>* Administered SC<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diffuse Systemic Sclerosis, Scleroderma, Systemic Sclerosis, Systemic Sclerosis-associated Interstitial Lung Disease