Clinical trial NCT02293915: An Efficacy and Safety Study of Sodium Oligo-mannurarate (GV-971) Capsule for the Treatment of Alzheimer's Disease
Official title: Phase III Study of Sodium Oligo-mannurarate (GV-971) Capsule on Mild to Moderate Alzheimer Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Mild to Moderate Alzheimer Disease
Cognitive Impairment
Lead sponsor: Shanghai Greenvalley Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2014-11-19
Enrollment: 818
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary purpose of this study is to determine the efficacy and safety of Sodium Oligo-mannurarate (GV-971) in 36-week treatment of mild to moderate Alzheimer's disease.


Eligibility criteria: Inclusion Criteria:

1. Aged 50-85 years (inclusive), no gender limitation;
2. Female subjects should be postmenopausal women (menopause \>24 weeks), surgically sterilized women or women of child bearing age who agree to take effective contraceptive measures during the trial. Women of child bearing age and women less than 24 weeks from menopause must undergo urine pregnancy test in screening period and result must be negative;
3. Subjects have received education in primary school and above and are able to complete protocol specified cognitive ability test and other tests;
4. Impaired memory for at least 12 months, with a tendency of progressive aggravation;
5. Meet diagnostic criteria of probable AD according to National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) (1984);
6. Patients with mild to moderate disease, i.e. 11 ≤total MMSE score ≤26 (for subjects with primary school education, 11 ≤total MMSE score ≤22);
7. Total Hachinski Ischemia Scale (HIS) score ≤4 ;
8. Total Hamilton Depression Scale/17-item (HAMD) score ≤10;
9. In screening, cranial MRI plain scan and oblique coronal hippocampus scan must be performed, lacunar infarction lesions with a diameter larger than 2 cm ≤2, without lacunar infarction lesion in vital sites, such as thalamus, hippocampus, entorhinal cortex, paraolfactory cortex, cortex and other subcortical gray matter nuclei; MRI shows highest possibility of Alzheimer's disease (medial temporal lobe atrophy visual rating scale MTA grade ≥2);
10. Neurological examination shows no significant sign;
11. Subjects should have stable, reliable caregivers, or at least have frequent contact with caregivers (at least 4 days every week, at least 2 h every day), and caregivers will help patients in participation in this study. Caregivers must accompany subjects to participate in study visits and have sufficient interaction and communication with subjects, so as to provide valuable information on NPI, ADCS-ADL, CIBIC-plus scales.
12. Before implementation of any protocol related procedure or examination, subjects must sign the written informed consent form. If subjects can not sign due to limited cognition, legal guardians should sign on behalf of subjects and meanwhile, legal guardians should also sign the informed consent form.

Exclusion Criteria:

1. Participate in another clinical trial within 30 days prior to initiation of this study;
2. Pregnant or nursing women;
3. Dementia due to other causes: vascular dementia, central nervous system infection (e.g. AIDS, syphilis), Creutzfeldt-Jakob disease, Huntington's chorea, Parkinson's disease, dementia with Lewy bodies, traumatic dementia, other physical and chemical factors (e.g. drug poisoning, alcoholism, carbon monoxide poisoning), significant physical illness (e.g. hepatic encephalopathy, pulmonary encephalopathy), intracranial occupying lesion (e.g. subdural hematoma, brain tumor), endocrine disorders (e.g. thyroid disease, parathyroid disease) and dementia caused by vitamin or other factors;
4. Previous nervous system disorders (including stroke, optic neuromyelitis, Parkinson's disease, epilepsy);
5. Abnormal laboratory values: liver function (ALT, AST) \> 1.5 times of upper limit of normal, Cr \> 1.5 times of upper limit of normal, white blood cell count, platelet, hemoglobin below the lower limit of normal, blood glucose \>1.5 times of upper limit of normal;
6. In screening, systolic blood pressure ≥160 mmHg or \<90 mmHg, or diastolic blood pressure ≥100 mmHg or \<60 mmHg;
7. Unstable or severe cardiac, pulmonary, hepatic, renal or hematopoietic disease (including unstable angina, uncontrolled asthma, active gastric bleeding and cancer), after 10 min rest, resting heart rate \<55 bpm;
8. Visual or hearing disorder, preventing completion of neuropsychological test and scale evaluation;
9. In screening, MRI examination shows significant focal lesions, more than 2 lacunar infarction lesions with a diameter \>2 cm, lacunar infarction lesions in vital sites, such as thalamus, hippocampus, entorhinal cortex, paraolfactory cortex, cortex and other subcortical gray matter nuclei; Fazekas scale for white matter lesions at ≥ grade 3;
10. Alcohol abuse or drug abuse;
11. Patients with psychosis, including severe depression;
12. Patients who are using drugs for Alzheimer's disease which can not be stopped;
13. Use of heparin, Propylene Glycol Mannurate Sulfate or Alginric Sodium Diester within 3 weeks prior to screening;
14. Inability to take trial drugs according to prescription, previous non-compliance with prescription or possibility of non-compliance with study treatment in the trial;
15. Investigators consider subjects can not complete this study;
16. Subjects in the phase II trial of the study drug;
17. Subjects are investigators participating in this study or their direct relatives, staff of Quintiles (Shanghai) or Shanghai Greenvalley Pharmaceutical Co., Ltd. or their direct relatives.

Primary outcomes:
measure: Improvement of Alzheimer's Disease Assessment Scale-cognitive subscale(ADAS-cog)/12 of sodium oligo-mannurarate capsule
timeFrame: 36 weeks
Secondary outcomes:
measure: Improvement of Clinician's Interview-Based Impression of Change Plus(CIBIC-plus) of sodium oligo-mannurarate capsule
timeFrame: 36 weeks
measure: Improvement of Alzheimer's Disease Cooperative Study/Activities of Daily(ADCS-ADL) of sodium oligo-mannurarate capsule
timeFrame: 36 weeks
measure: Improvement of Neuropsychiatric Inventory(NPI) of sodium oligo-mannurarate capsule
timeFrame: 36 weeks
measure: Glucose metabolism of bilateral temporoparietal cortex
timeFrame: 36 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing
state: Beijing
city: Chongqing
country: China
facility: Chongqing
state: Chongqing
city: Fuzhou
country: China
facility: Fujian
state: Fujian
city: Guangzhou
country: China
facility: Guangzhou
state: Guangdong
city: Wuhan
country: China
facility: Wuhan
state: Hubei
city: Changsha
country: China
facility: Changsha
state: Hunan
city: Nanjing
country: China
facility: Nanjing
state: Jiangsu
city: Suzhou
country: China
facility: Suzhou
state: Jiangsu
city: Yangzhou
country: China
facility: Yangzhou
state: Jiangsu
city: Jinan
country: China
facility: Jinan
state: Shandong
city: Shanghai
country: China
facility: Shanghai
state: Shanghai
city: Xi'an
country: China
facility: Xi'an
state: Shanxi
city: Chengdu
country: China
facility: Sichuan
state: Sichuan
city: Tianjin
country: China
facility: Tianjin
state: Tianjin
city: Hangzhou
country: China
facility: Hangzhou
state: Zhejiang
city: Wenzhou
country: China
facility: Wenzhou
state: Zhejiang
Study officials:
References:
citation: Ferrari C, Sorbi S. The complexity of Alzheimer's disease: an evolving puzzle. Physiol Rev. 2021 Jul 1;101(3):1047-1081. doi: 10.1152/physrev.00015.2020. Epub 2021 Jan 21.