A Phase 3 Study of AGA111 in Patients With Degenerative Disc Disease Undergoing Lumbar Interbody Fusion

Study Overview
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Brief Summary
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The primary objective of the study is to assess the overall efficacy of a single intervertebral local administration of AGA111 in patients with degenerative disc disease undergoing lumbar interbody fusion.

Detailed Description
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This is a phase 3, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of a single intervertebral local administration of AGA111 in patients with degenerative disc disease undergoing lumbar interbody fusion. About 400 subjects who meet the eligibility criteria will be randomly assigned to the following two treatment groups in a 1:1 ratio.

Official Title
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A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of a Single Lntervertebral Local Administration of AGA111 in Patients With Degenerative Disc Disease Undergoing Lumbar Lnterbody Fusion

Conditions
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Degenerative Disc Disease

Intervention / Treatment
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* Drug: AGA111
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has degenerative disc disease of L3-S1 with low back pain, with or without a history of radiating leg or buttock pain, paresthesia, numbness or weakness secondary to radiculopathy of the corresponding spinal segment; Has radiographic evidence (e.g., X-ray and CT/magnetic resonance imaging MRI) of degenerative disc disease; Adults ≥ 18 and ≤ 80 years of age and skeletally mature at the time of surgery; Plan to undergo a single-level lumbar interbody fusion; Preoperative ODI score ≥ 30; Has not respond to conservative treatment (e.g, bed rest, physical therapy, drugs, local injections, manipulation and other non-surgical treatments) for a period of at least 3 months; Willing and able to comply with the protocol and able to understand and sign the subject's informed consent form (ICF) ; Female subjects of child-bearing potential must agree to use a highly effective method of birth control during the study and for 1 year after the administration of investigational drug, and must have a negative pregnancy test prior to the randomization. Exclusion Criteria: Has undergone other decompression, fusion, and/or other non-fusion spinal surgery at the spinal segment intended to undergo the surgery prior to the screening (except for transforaminal endoscopic discectomy); Known other significant lumbar instability; Lumbar scoliosis > 30 degrees (evaluated by investigators); Presence of active malignancy or prior history of malignancy; Overt or active infection, either local to surgical space or systemic; Patients with a dual-energy X-ray absorption (DXA) total hip T-score ≤ -3.0; Body weight index (BMI) <18.5 kg/m2 or BMI > 35 kg/m2; Have received other treatments affecting fusion surgery, such as radiotherapy near the surgical site; Presence of other co-morbidities of the spine or upper/lower extremities that may affect the investigator's assessment of the lumbosacral nervous system and/or pain; Presence of mental disease or psychiatric condition that interferes with the patient's self-assessment of function, pain, or quality of life; History of progressive osseous heteroplasia or fibrodysplasia ossificans progressiva; Known hypersensitivity or allergy to bone morphogenetic protein (BMP) products or their excipient; and/or instrumentation materials in surgery, e.g., titanium, titanium alloy, cobalt chrome, cobalt chrome alloy, or polyetheretherketone (PEEK); Pregnant or lactating women; or plan to become pregnant within 1 year following the study surgery. Other conditions that, in the opinion of the investigator, would interfere with the subject's ability to comply with the protocol, and other conditions that will make the subject inappropriate for participation in the study as judged by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

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 |
| --- | --- |
| Experimental: AGA111<br>AGA111 in autologous blood coagulum (ABC) is locally delivered at the intervertebral space. | Drug: AGA111<br>* AGA111 is locally administered in an ABC carrier at the intervertebral space during the lumbar interbody fusion.<br>|
| Placebo Comparator: Placebo<br>Placebo in ABC is locally delivered at the intervertebral space. | Drug: Placebo<br>* Placebo is locally administered in an ABC carrier at the intervertebral space during the lumbar interbody fusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall success rate: Proportion of subjects who achieve overall success. |  | Up to 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Success rate of radiographic fusion |  | Up to 52 weeks | 
| Mean change of ODI score |  | Up to 52 weeks |