A Study of the Efficacy and Safety of GB-0998 in Patients With Unexplained Recurrent Miscarriage

Study Overview
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Brief Summary
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The present survey was conducted to evaluate the efficacy and safety of GB-0998(immunoglobulin) in the treatment of unexplained recurrent miscarriage in comparison to placebo using a multicenter, double-blind, intergroup comparison method.

Detailed Description
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Among the patients whose risk factors for recurrent miscarriage are unknown who repeatedly miscarry or patients who repeatedly miscarry despite treatment for risk factors, those who have never given birth and have had four or more miscarriages. Patients were assigned into two groups, GB-0998 or placebo, and received 8 ml/kg body weight of GB-0998 (400 mg/kg body weight) or placebo once a day for 5 days. The primary efficacy endpoint was ongoing pregnancy rate at 22 weeks of gestation (excluding miscarriages associated with fetal chromosomal abnormalities) and one of the secondary endpoint was live birth rate.

Official Title
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A Double-Blind, Randomized, Placebo-Controlled Study of GB-0998 in Patients With Unexplained Recurrent Miscarriage.

Conditions
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Recurrent Miscarriage

Intervention / Treatment
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* Drug: GB-0998
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Patients with primary recurrent miscarriage Patients with a history of at least 4 miscarriages (not including biochemical pregnancy in the count of prior miscarriages) Patients with any of the following risk factors for recurrent miscarriage 【Patients with unknown risk factors】 Patients with normal test results for each of the following risk factors who have experienced miscarriage of a fetus with normal chromosome karyotype Abnormal uterine morphology Thyroid dysfunction Chromosome abnormality in the couple Positive antiphospholipid antibody Factor XII deficiency Protein S deficiency Protein C deficiency 【Patients determined to have risk factors】 Patients with the following risk factors who have experienced miscarriage of a fetus with normal chromosome karyotype despite receiving treatment for these factors Abnormal uterine morphology (septate uterus): Patients who have undergone surgery Thyroid dysfunction: Patients receiving medical treatment Incidentally positive antiphospholipid antibody, factor XII deficiency, protein S deficiency, protein C deficiency:Patients receiving combination therapy with aspirin and heparin 4．Regardless of whether or not risk factors are present, patients should have experienced at least 1 a miscarriage of a fetus with normal chromosome karyotype 5．Patients below the age of 42 years at the time of obtaining informed consent 6．Patients who can be admitted for at least the period from the start date of administration of the study drug to the date of examination and assessment 1 week after the start of administration of the study drug 7．Patients who have given written informed consent to participate in this study Exclusion Criteria: Patients with chromosome abnormalities in themselves or their partners that are risk factors for recurrent miscarriage, patients with antiphospholipid syndrome, and patients with incidentally positive antiphospholipid antibody (when the latest test result is positive) Patients in whom complications of diabetes mellitus or impaired glucose tolerance has been identified, but who have not received appropriate treatment for this condition Patients who have received intravenous immunoglobulin therapy as treatment for recurrent miscarriage in the past Patients with a history of stillbirth at 22 weeks of gestation or later Patients receiving treatment for malignant tumor Patients with a history of thromboembolism Patients with a history of shock or hypersensitivity in response to the ingredients of this drug or patients with hereditary fructose intolerance Patients who have been diagnosed with IgA deficiency in the past or patients who have a serum IgA level of <5 mg/dL at laboratory tests at registration Patients who have received another study drug within the period of 12 weeks prior to informed consent or who are currently participating in another clinical trial Patients who are unsuitable for this study for any other reason, in the opinion of a principal investigator or sub-investigators

Ages Eligible for Study
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Maximum Age: 41 Years

Sexes Eligible for Study
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Female

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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Infusion of normal saline | Drug: Placebo<br>* Subjects received the same dose of saline as GB-0998 for 5 days after confirmation of the gestational sac by ultrasonography, up to 6 weeks and 6 days of gestation.<br>* Other names: normal saline;|
| Experimental: GB-0998<br>Infusion of GB-0998 (Immunoglobulin) | Drug: GB-0998<br>* Subjects received GB-0998 at 400 mg/kg body weight once daily for 5 days until 6 weeks and 6 days of gestation after confirmation of the gestational sac by ultrasonography.<br>* Other names: Intravenous Immunoglobulin （Venoglobulin®IH，2.5g/50ml）;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ongoing pregnancy rate (excluding miscarriages associated with fetal chromosomal abnormalities) | To evaluate the effectiveness of the drug in preventing miscarriages, we examined the ongoing pregnancy rate at 22 weeks and 0 days of gestation in cases excluding cases of fetal chromosome aberration miscarriages. | At 22 weeks of gestation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ongoing pregnancy rate(all patients) | To evaluate the effectiveness of the drug in preventing miscarriages, we examined the ongoing pregnancy rate at 22 weeks and 0 days of gestation in all patients. | At 22 weeks of gestation | 
| Live birth rate (excluding miscarriages associated with fetal chromosomal abnormalities) | To evaluate the effectiveness of the drug in total outcome of pregnancy, we examined the live birth rate in cases excluding cases of fetal chromosome aberration miscarriages. | At the time of birth | 
| Live birth rate(all patients) | To evaluate the effectiveness of the drug in total outcome of pregnancy, we examined the live birth rate in all patients. | At the time of birth | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IVIG, Unexplained Recurrent miscarriage, Primary Recurrent miscarriage, Intravenous immunoglobulin