Phase III Randomized, Double-Blind, Placebo-Controlled Study of Mocravimod as Adjunctive and Maintenance Therapy in Acute Myeloid Leukemia Undergoing Allo-HCT
- Trial ID
- 2024-512752-38-00
- Protocol
- PKRPC001
- Sponsor
- Priothera S.A.S.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this phase III study is to compare the **efficacy** of **mocravimod** to that of placebo in adult patients with acute myeloid leukemia (AML) undergoing allogeneic hematopoietic cell transplantation (HCT). This comparison is clinically relevant as it aims to determine the potential benefit of mocravimod as an adjunctive and maintenance treatment, which could improve patient outcomes in this high-risk population.
Secondary objectives include:
- Comparing mocravimod's effect on overall survival (OS) to that of placebo.
Participants
The clinical trial involves a total of **183 participants** who are being studied to compare the efficacy of mocravimod to that of placebo as an adjunctive and maintenance treatment to **hematopoietic cell transplantation (HCT)**. The study population includes both male and female subjects, aged between 18 and 75 years, with a diagnosis of acute myeloid leukemia (AML), excluding acute promyelocytic leukemia, as per the World Health Organization (WHO) 2022 classification. Participants are selected based on specific criteria, including those with European LeukemiaNet (ELN) high risk or intermediate risk, or AML in complete remission (CR1), or AML of any risk in CR2, with complete remission defined by specific hematological parameters. The trial includes individuals with a life expectancy of at least six months and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. The selection process also considers the planned use of a related or unrelated donor with no more than one antigen mismatch or a haploidentical donor. The trial population is characterized by a vulnerable group, reflecting the serious nature of the condition being studied. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data. The sponsor has not provided additional information regarding lifestyle considerations or other demographic details.
Plans and Procedures
The clinical trial is a **randomized**, **double-blind**, placebo-controlled, multi-center phase III study designed to evaluate the efficacy and safety of **mocravimod** as an adjunctive and maintenance treatment in adult patients with acute myeloid leukemia (AML) undergoing allogeneic hematopoietic cell transplantation (HCT). The trial aims to compare the efficacy of mocravimod to that of a placebo, with the primary endpoint being relapse-free survival (RFS). Secondary endpoints include overall survival (OS), RFS at the end of the study, survival free from Grade III/IV acute graft-versus-host disease (aGvHD) at 12 months, and survival free from moderate/severe chronic graft-versus-host disease (cGvHD) at the end of the study.
The trial is expected to run from July 2022 to April 2027, with participants involved for a maximum treatment period of 12 months. The study will include an initial screening visit to confirm eligibility based on criteria such as a diagnosis of AML according to the World Health Organization (WHO) 2022 classification, planned use of a related or unrelated donor, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Participants must be aged between 18 and 75 years and have a life expectancy of at least 6 months at screening.
Following the screening visit, participants will be randomized to receive either mocravimod or a placebo, administered orally in capsule form. The study will include regular follow-up visits to monitor the participants' health, assess the efficacy of the treatment, and record any adverse events. The end-of-study visit will evaluate the long-term outcomes and safety of the treatment. Participants may be withdrawn from the study early if they experience significant adverse effects, fail to comply with the study protocol, or if the investigator deems it necessary for their safety.
Treatment
The clinical trial involves the administration of **Mocravimod (KRP203)**, an experimental medication, in the form of **capsules**. The active substance, **mocravimod**, is of chemical origin. The medication is administered orally with a maximum daily dose of 3.00 mg, and the total dose over the treatment period should not exceed 1095.00 mg. The treatment period is set for a maximum of 12 months. The pharmaceutical form is specifically designed for adult patients and is not a pediatric formulation. The study aims to evaluate the efficacy and safety of mocravimod as an adjunctive and maintenance treatment in adult patients with acute myeloid leukemia (AML) undergoing allogeneic hematopoietic cell transplantation (HCT).
The trial also includes a **placebo** group, which consists of hard capsules containing maize starch, microcrystalline cellulose, and magnesium stearate. These capsules do not contain any active pharmaceutical ingredient and are used to maintain the double-blind nature of the study. The placebo is administered in a manner identical to the experimental medication to ensure consistency in the trial's methodology. The placebo capsules are also not a pediatric formulation and are intended for adult use only. Compliance with the dosing schedule and administration is monitored throughout the study to ensure adherence to the protocol.
Efficacy
The efficacy of mocravimod as an adjunctive and maintenance treatment in adult patients with acute myeloid leukemia (AML) undergoing allogeneic hematopoietic cell transplantation will be assessed through a prospective, randomized, double-blind, placebo-controlled, multi-center phase III study. The primary endpoint for evaluating efficacy is **Relapse-free survival (RFS)**. Secondary endpoints include Overall Survival (OS), RFS at the end of the study (EOS), survival free from Grade III/IV acute Graft-versus-Host Disease (aGvHD) at 12 months, time to acute GvHD, survival free from moderate/severe chronic GvHD (cGvHD) at EOS, time to cGvHD, and GvHD-free, Relapse-free survival (GRFS) at 12 months and at EOS.
Data collection will occur at specified timepoints throughout the study, including assessments at 12 months and at the end of the study. The analysis will compare the efficacy of mocravimod to that of a placebo, focusing on the aforementioned endpoints. The study is designed to ensure rigorous evaluation of mocravimod's impact on survival and disease progression in the specified patient population.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Subjects with a diagnosis of AML (excluding acute promyelocytic leukemia) according to the World Health Organization (WHO) 2022 classification of AML and related precursor neoplasms, including therapy AML with myelodysplasia related gene mutations.
- Subjects with European LeukemiaNet (ELN) high risk or intermediate risk or AML in CR1, or AML of any risk in CR2. (Complete remission with incomplete count recovery [CRi] is also allowable). - Complete remission is defined as: < 5% marrow blasts by morphologic examination and no circulating peripheral blasts; absence of extramedullary disease; absolute neutrophil count ≥ 1.0x109/L (1000/μL); platelet count ≥ 100x109/L (100 000/μL) - CRi is defined as meeting all complete remission criteria except for residual absolute neutropenia < 1000/μL and/or thrombocytopenia <100 000/μL
- Planned use of a related or unrelated donor or with no more than 1 antigen mismatch or planned use of a haploidentical donor
- Life expectancy ≥ 6 months at screening.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Male or female, age ≥ 18 years and ≤ 75 years.
Exclusion Criteria
- Planned use of CsA, anti-thymocyte globulin (ATG), alemtuzumab, abatacept for GvHD prophylaxis.
- Cardiac dysfunction
- Pulmonary dysfunction.
- Significant liver disease or liver injury or known history of alcohol abuse, chronic liver or biliary disease. Hepatic dysfunction as defined by aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 2.5 x upper limit of normal (ULN); or total bilirubin > 1.5 x ULN
- Renal dysfunction with creatinine clearance < 45 mL/min by the Cockcroft-Gault formula.
- History of stroke or intracranial hemorrhage within 1 year prior to screening.
- Active clinically significant infection (viral, bacterial, or fungal) that requires ongoing antimicrobial therapy and in the judgment of the investigator represents a risk to proceeding with HCT.
- Planned use of serotherapy during conditioning, including ATG and alemtuzumab.
- Planned ex vivo major graft manipulation, including T-cell depletion or CD34+ selection.
- Subjects having received prior allogeneic HCT or recipients of a solid organ transplant.
- Immunosuppressive drugs for concomitant disease. Subjects must be able to be off prednisone (> 10 mg/day) or other immunosuppressive medications for at least 3 days prior to the start of treatment of the study. Physiologic replacement dosing of hydrocortisone is permissible.
- Require treatments for cardiac dysfunction
- Subjects with acute promyelocytic leukemia.
- Blast crisis of chronic myeloid leukemia
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Recruiting | 01 Jul 2022 | 40 |
 Germany | Recruiting | 01 Jul 2022 | 20 |
 Italy | Recruiting | 01 Jul 2022 | 20 |
 Poland | Recruiting | 01 Jul 2022 | 20 |
 Romania | Recruiting | 01 Jul 2022 | 8 |
 Spain | Recruiting | 01 Jul 2022 | 30 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Hard capsules containing maize starch, microcrystalline cellulose, magnesium stearate | Placebo | N/A | — | — | — | N/A |
MocravimodKRP203 | Test | CAPSULES | ORAL USE | 3.00 | 12 | PRD9710650 |