A Phase I/II Study of AGA111 for Lumbar Interbody Fusion in Patients With Degenerative Disc Disease

Study Overview
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Brief Summary
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The objectives of the study are to evaluate the safety and preliminary efficacy of a single administration of AGA111 for lumbar interbody fusion in patients with degenerative disc disease.

Detailed Description
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A randomized, double-blind, placebo-controlled, phase 1/2 study to evaluate the safety and preliminary efficacy of single administration of AGA111 for lumbar interbody fusion in patients with degenerative disc disease. A total of 60 participants will be enrolled and randomized to placebo, AGA111 0.25 mg, or AGA111 0.5 mg at 1: 1: 1 ratio. All participants will undergo lumbar interbody fusion and receive study treatment during the surgery.

Official Title
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A Randomized, Double-blinded, Placebo-controlled, Phase I/II Study to Evaluate the Safety and Preliminary Efficacy of Single Administration of AGA111 for Lumbar Interbody Fusion in Patients With Degenerative Disc Disease

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: Willing and capable of giving signed informed consent. Male or female, age between 40-80 years. Male or female of childbearing potential must agree to use a highly effective contraception throughout the entire study period, and female subjects must have a negative pregnancy test prior to the randomization. Has degenerative disc disease (DDD) of the lumbosacral(L3-S1) spine that results in back pain, with or without radiating leg pain. Has radiographic evidence (e.g. CT, MRI, x-ray, etc.) of degenerative disc disease. Planning to receive single-level lumbar interbody fusion. Willing and capable of adhering to the protocol and visit schedule. Exclusion Criteria: Prior surgical procedure at the involved or adjacent spinal levels. Presence or prior history of inflammatory disease of the spine. Presence or prior history of neoplastic disease of the spine. BMI <18.5 or BMI >35. Documented titanium allergy or intolerance. Presence or prior history of malignancy (except for fully resected basal cell carcinoma of the skin). Presence or history of an uncontrolled, unstable, clinically significant medical condition that, in the opinion of the investigator, could jeopardize or compromise the subject's safety or ability to participate in this study. Active local or systemic infection. Female subject who is pregnant or lactating. Serological evidence of positive human immunodeficiency virus (HIV) antibody. HBsAg positive or HBeAg positive, along with positive HBV DNA test. Serological evidence of HCV antibody, along with HCV RNA > lower limit of detection. Known drug or alcohol abuser.

Ages Eligible for Study
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Minimum Age: 40 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: 0.25 mg AGA111<br>0.25 mg 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>|
| Experimental: 0.5 mg AGA111<br>0.5 mg AGA111 in ABC is locally delivered to the participants 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 |
| --- | --- | --- |
| Number of participants with adverse events (AEs) | An adverse event (AE) is any untoward medical occurrence in clinical study participant, temporally associated with the use of the investigational product (IP), whether or not considered related to the IP. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of IP. | Up to 12 months | 
| Number of participants who develop anti-drug antibody to AGA111 | Blood samples taken prior to the operation and 5 days, 28 days and 90 days post operation were tested for anti-AGA111 antibodies using an immunoassay method. | Up to 90 days post operation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiographic fusion success | Radiographic fusion success is defined as evidence of continuous bone bridging from the superior to the inferior vertebrae via CT evaluation and no evidence of motion as defined by less than 3mm translational motion and less than 5° in angular motion at the treated level via hyperextension and hyperflexion X-rays. | Up to 12 months post operation | 
| New Bone formation | New bone formation is defined as the ratio of successful fusion area to the total area in the transverse plane of CT scan. | Up to 12 months post operation | 
| Oswestry Disability Index (ODI) | The change of point in ODI from baseline. | Up to 12 months post operation | 
| Pain score through Visual Analogue Scale (VAS) | The change of point in VAS from baseline. | Up to 12 months post operation | 
| Maximum Concentration (Cmax) of AGA111 | Maximum concentration of AGA111 after dosing. | 90 minutes before administration, and 30 minutes, 1 hour, 6 hours, and 24 hours post administration. | 
| Time to maximum concentration (Tmax) of AGA111 | Time to maximum concentration of AGA111 after dosing. | 90 minutes before administration, and 30 minutes, 1 hour, 6 hours, and 24 hours post administration. | 
| Area under the concentration time curve (AUC) | Definite integral of the curve describing the variation of AGA111 in blood as a function of time. | 90 minutes before administration, and 30 minutes, 1 hour, 6 hours, and 24 hours post administration. |