A Clinical Study to Evaluate the Long-Term Safety Sodium Oligomannate Capsules (GV-971)

Study Overview
=================
Brief Summary
-----------------
A clinical study to evaluate the long-term safety of Sodium Oligomannate Capsules (GV-971)

Detailed Description
-----------------
Sodium oligomannate (Code: GV-971), a marine-derived oligosaccharide after extraction, separation and degradation from algae, can play a role in the treatment of Alzheimer's disease by reconditioning the dysbiosis of gut microbiota, preventing peripheral immune cells from invading the brain, inhibiting the inflammatory response in the brain, and targeting protein folding errors in the brain tissue. Phase I clinical study shows GV-971 was safe and tolerated in healthy adult volunteers when administered continuously at 1200 mg/dose or 1500 mg/day (750 mg/dose, bid) for 5 days. Phase II and III clinical studies show that the treatment of GV-971 at 900 mg/day dosage for 36 weeks can significantly improve the cognitive function of patients with mild to moderate Alzheimer's disease (AD) and was safe and well-tolerated. Sodium Oligomannate Capsules obtained approval from China's National Medical Products Administration (NMPA) on November 2, 2019, with approval letter number of 2019S00571. This product is a chemical drug with a registration classification of 1.2. It is approved for the clinical indication of mild to moderate Alzheimer's disease and the function of improving the cognitive function of patients. The clinical dosage and administration is 3 capsules (450 mg)/time, bid, po. Due to the limited number of subjects and observation period of medication in completed GV-971 clinical studies, and the screening of patients with the strict inclusion and exclusion criteria, the adverse reactions and long-term safety of GV-971 cannot be comprehensively observed and recorded. Therefore, according to the requirements of the NMPA for the marketing of new drugs, this study is intended to further carry out a post-marketing investigation on expanded population using a design of a 96-week intensive monitoring clinical trial to determine the incidence of known adverse reactions of GV-971 under long-term administration, observe the occurrence of new adverse reactions, analyze the correlation, incidence, severity, and risk factors of adverse reactions/events, and better guide the rational use of drugs in clinical practice.

Official Title
-----------------
A Clinical Study to Evaluate the Long-Term Safety Sodium Oligomannate Capsules

Conditions
-----------------
Alzheimer Disease

Intervention / Treatment
-----------------
* Drug: Sodium Oligomannate Capsules


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects eligible for this study must meet all of the following criteria: ≥18 years of age; Signed informed consent form; Patients receiving GV-971 treatment prescribed by clinicians; Exclusion Criteria: A subject may be excluded from participation in the study if any of the following apply: Patients who may be allergic to Sodium Oligomannate Capsules as judged by the investigator; Female participants who are pregnant or lactating; Patients who cannot cooperate to complete the follow-up inquiries; Any other diseases or conditions that are inappropriate to participate in this clinical trial in the opinion of the investigator.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GV-971<br>The recommended dose regimen for subjects: GV-971 450 mg (3 capsules) per dose, bid, po. in morning and evening | Drug: Sodium Oligomannate Capsules<br>* Sodium Oligomannate Capsules, each capsule contains 150 mg of sodium oligomannate. The recommended treatment is oral administration, 450 mg (3 capsules) per dose, bid, in morning and evening.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Long-term safety of GV-971 in clinical practice during 48 weeks | The incidence of adverse reactions and AE/SAE in patients treated with GV-971 during the 48-week monitoring period | Week 48 | 
| Long-term safety of GV-971 in clinical practice during 96 weeks | The incidence of adverse reactions and AE/SAE in patients treated with GV-971 during the 96-week monitoring period | Week 96 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Endpoints: Vital signs, laboratory tests , electrocardiogram, and early withdrawal from the study during 48 weeks | The incidence of adverse events and adverse reactions in patients with liver insufficiency and renal insufficiency receiving GV-971 during 48 weeks | 48-week | 
| Safety Endpoints: Vital signs, laboratory tests , electrocardiogram, and early withdrawal from the study during 96 weeks | The incidence of adverse events and adverse reactions in patients with liver insufficiency and renal insufficiency receiving GV-971 during 96 weeks | 96-week |