Adults with Warm Autoimmune Hemolytic Anemia MedDRA version: 20.1 Level: LLT Classification code 10002285 Term: Anemia hemolytic autoimmune (NOS) System Organ Class: 100000004851
Conditions
Interventions
Product Name: M281
Product Code: M281
Pharmaceutical Form: Solution for injection
INN or Proposed INN: N/A
CAS Number: 2211985-36-1
Current Sponsor code: M281
Other descriptive name: M281
Concentratio
Sponsors
Momenta Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria - 1. Male or female =18 years of age. 2. Diagnosed with active primary or secondary wAIHA, defined as having all of the following: a.Hemoglobin level <9 g/dL or <10 g/dL if symptomatic or on corticosteroids/immunosuppressants AND b.Signs of hemolysis, defined as: lactate dehydrogenase (LDH) levels above the upper limit of normal (ULN), or haptoglobin below the lower limit of normal, or total bilirubin above the ULN AND c.Serological evidence of anti-erythrocyte antibodies associated with a positive DAT that is either positive for IgG only or is positive for IgG and C3d (fragment of the third component of complement) at time of diagnosis. 3.Has been diagnosed with wAIHA for at least 3 months, has received standard of care treatment for wAIHA but is not currently under adequate control 4.If on corticosteroids, are on a dose that has been stable for at least 14 days prior to randomization. 5.If currently receiving immunosuppressants, has been on a stable dose for 30 days prior to Screening. Allowed concomitant immunosuppressants are azathioprine, mycophenolate mofetil/mycophenolic acid, cyclosporine, cyclophosphamide. 6.Have a platelet count =30 × 109/L. 7.Have screening serum albumin and serum calcium concentrations within the normal range. 8.Have screening total serum IgG of at least 600 mg/dL. 9.Have a screening creatine kinase (CK) value <2 × ULN. 10.Have a negative QuantiFERON®-TB Gold test. 11.Patients who have undergone splenectomy must be at least 3 months post resection prior to screening and must be vaccinated as per the United States Center for Disease Control and Prevention (CDC) annual Recommended Immunization Schedule for Adults Aged 19 Years or Older, United States 12.Patients with autoimmune disease (eg, systemic lupus erythematosus or rheumatoid arthritis) and lymphoproliferative disorders may be eligible if they are stable (no changes in concomitant disease-related medications and severity of disease for at least 3 months). Patients with lymphoproliferative disease must have a low grade, be stable and be, in the opinion of the Investigator, unlikely to require chemotherapy or monoclonal antibody therapy during the study. Patients requiring change of treatment or new treatment (but not rescue therapy) during the study will be terminated from the study 13.Have sufficient venous access to allow drug administration by IV infusion and blood sampling as per the protocol. 14.Women of childbearing potential (WOCBP), defined as women physiologically capable of becoming pregnant, must have a negative serum pregnancy test at screening and a negative urine pregnancy test at Baseline. Menopausal women must have an elevated serum folliclestimulating hormone (FSH) level at Screening; if the FSH is not elevated, they are considered to be of childbearing potential and must have a negative serum pregnancy test at screening and a negative urine pregnancy test at Baseline to be eligible. 15.Women of childbearing potential (including menopausal women who do not have elevated FSH) must agree to remain totally abstinent (ie, refrain from sexual intercourse during the study) or to consistently use a reliable and highly effective method of contraception (eg, condom plus diaphragm, condom plus spermicide, diaphragm plus spermicide, or intrauterine device or oral/injectable/implanted hormonal contraceptive used in combination with an additional barrier method) during the
Exclusion criteria
Exclusion criteria: Exclusion Criteria - 1.Have received a transfusion within 30 days prior to randomization. 2.Have any other associated cause of hereditary or acquired hemolytic anemia. 3.Have received rituximab within 6 months prior to randomization. Note: Patients who received rituximab within 3 months but have evidence of worsening hemolysis (defined as LDH levels above ULN or haptoglobin levels below the lower limit of the normal range (LLN) or total bilirubin levels above the ULN) may be included in the study. 4. Has received IVIG within 6 weeks prior to randomization on Day 1. The patient may be re-screened after the exclusionary period of 6 weeks has passed. 5.Have cold antibody AIHA, cold agglutinin syndrome, mixed type (ie, warm and cold) AIHA, or paroxysmal cold hemoglobinuria. 6.Have a severe infection (eg, pneumonia, biliary tract infection, diverticulitis, Clostridium difficile infection) that requires parenteral anti-infectives and/or hospitalization, and/or is assessed as serious/clinically significant by the Investigator, within 8 weeks prior to screening. The patient may be re-screened after the 8 week exclusionary period has passed. Any patient with an infection requiring oral antiinfectives (eg, sinusitis, bronchitis, uncomplicated urinary tract infection) within 4 weeks prior to screening will be excluded, but may be subsequently re-screened after the 4 week exclusionary period has passed. 7.Have a chronic infection (eg, bronchiectasis, chronic osteomyelitis, chronic pyelonephritis) or require chronic treatment with anti-infectives (eg, antibiotics, antivirals). 8.Have received a live vaccine within 3 months prior to screening, or have a known need to receive a live vaccine during the study or within at least 3 months after the last dose of study drug. The patient may be re screened after the 3 month exclusionary period has ended. 9. Has any confirmed or suspected clinical immunodeficiency syndrome not related to treatment of his/her wAIHA, or has a family history of congenital or hereditary immunodeficiency unless confirmed absent in the patient. 10.Have a known history of, or positive test result for human immunodeficiency virus-1 (HIV 1) and HIV 2 antibodies, hepatitis B virus (HBV core antigen), or hepatitis C virus (HCV). Note: Patients with past HCV may be included in the study if they have a documented negative HCV ribonucleic acid level in the serum at 12 weeks or longer after the completion of HCV therapy. 11.Are currently breastfeeding, pregnant, intend to become pregnant during the study, or are planning egg donation during the study or within 30 days after the last dose of study drug. 12.Have current alcohol/substance abuse/dependence, a history of alcohol/substance abuse/dependence within the 12 months prior to screening, or, in the Investigator's opinion, show evidence of ongoing alcohol/substance abuse/dependence. 13.Are currently participating in another interventional clinical trial or have received any investigational drug within the past 3 months. 14.Have had any major surgery within 3 months prior to screening or have plans for or have been scheduled for any elective surgery or major dental procedure during the study. 15.Have a history of a major organ transplant (eg, heart, lung, kidney, liver), or hematopoietic stem cell/marrow transplant. 16.Have a history of severe and/or uncontrolled hepatic, gastrointestinal, renal, pulmonary, cardiovascular, psychiatric,
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): The primary efficacy endpoint is the attainment of the following at 3, where at least the first is consecutive visits at or before Week 16 without the need of rescue therapy: • Hgb level =10 g/dL AND • An increase from baseline in Hgb =2 g/dL The first of the three consecutive visits must be at or before week 16 in order to qualify for success in the primary efficacy endpoint. For example, if a patient attained the above criteria at weeks 18, 20, and 22 and not before, this patient would not be considered a success. If the patient attained the criteria at weeks 16, 18, and 20, the patient would be considered a success. In case 1 of the 3 consecutive Hgb observations is missing and the other 2 met the above criteria, the next non-missing Hgb observation must also meet the criteria in order for the patient to qualify as a success in the primary efficacy endpoint. No more than 1 missing observations is allowed. For example, if a patient met the criteria at weeks 14, 16, and 20, and with a missing value at week 18, this patient would be considered a success in the primary efficacy endpoint. If the patient met the criteria at weeks 14, 18, and 22, but with missing data at weeks 16 and 20, the patient would not be considered a success. Patients who took rescue therapy before reaching the criteria will be treated as having failed the primary efficacy outcome. If a patient has missing Hgb at both baseline and screening but is randomized by mistake, the patient will be excluded from the ITT analysis. This situation is unlikely to happen because the IVRS system requires screening Hgb for randomization to occur.;Timepoint(s) of evaluation of this end point: The first of the three consecutive visits must be at or before week 16 in order to qualify for success in the primary efficacy endpoint. In case 1 of the 3 consecutive Hgb observations is missing and the other 2 met the above criteria, the next non-missing Hgb observation must also meet the criteria in | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The following are secondary efficacy outcome measures: • Change in oral corticosteroid use o Overall percentage of patients that achieved any reduction in the daily dose of corticosteroids while maintaining Hgb response from baseline to the end of the double-blind period o Percent reduction in daily corticosteroid dose in each group between baseline and the end of the double-blind period • Association between IgG reduction and Hgb/hemolysis parameters o Hgb range at steady state (estimated using a model-based longitudinal analysis of Hgb/hemolysis parameters in relationship to IgG level and dose regimen) • Normalization of Hgb level o Hgb level and change from baseline in Hgb level through Week 16 o Hgb level and change from baseline in Hgb level throughout the study • Normalization of hemolytic markers o Attainment of a 2 g/dL Hgb increase from baseline AND normal LDH and haptoglobin levels at any time during the study o Attainment of a 2 g/dL Hgb increase from baseline AND normal LDH and haptoglobin levels at 3 consecutive visits • Duration of response o Duration from the first time point at which the criteria for the primary efficacy endpoint is met until the time point at which it is no longer met o Females: attainment and maintenance of a Hgb level of 11 g/dL during the 24 week double-blind period; Males: attainment and maintenance of a Hgb level of 12 g/dL during the 24 week double-blind period • Change in the level of patient fatigue o Change from baseline in the total score from the FACIT-Fatigue Scale at the end of the double-blind period. Secondary endpoints will be summarized descriptively. Categorical variables will be summarized by treatment group using frequencies and percentages. Differences between each M281 group and placebo will be summarized as differences in proportions. Baseline adjusted estimates of the treatment effect of each M281 group versus placebo will also be derived using logisti | — |
Countries
Czech Republic, Denmark, France, Germany, Greece, Hungary, Italy, Netherlands, Poland, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trial Information Desk
Momenta Pharmaceuticals, Inc.
Outcome results
None listed