What Is AVA6000?
AVA6000 is an investigational medication being studied for various types of cancer. It is a specialized form of doxorubicin, a well-known chemotherapy drug. AVA6000 is designed to be "FAP-activated," meaning it is specifically activated by Fibroblast Activation Protein (FAP). FAP is a protein often found in the microenvironment surrounding many solid tumors. This design aims to deliver the active chemotherapy agent more precisely to cancer cells, potentially reducing side effects on healthy tissues.
Currently, AVA6000 is under investigation in a single clinical trial involving 158 participants. This trial is exploring its potential use in treating several cancers, including breast cancer, ovarian carcinoma, salivary gland tumors, soft tissue sarcoma, and urothelial carcinoma. The development of AVA6000 is sponsored by Avacta Life Sciences Ltd.
Uses and Conditions Under Study
AVA6000 is currently being investigated in clinical trials for its potential to treat several types of cancer. The drug is designed as a FAP-activated doxorubicin, which means it aims to deliver chemotherapy more specifically to tumors that express Fibroblast Activation Protein (FAP). This targeted approach may enhance the drug's effectiveness against cancer cells while potentially minimizing harm to healthy tissues.
One condition under study is Breast Cancer. This common cancer originates in the breast tissue and can spread to other parts of the body. AVA6000 is being explored for its ability to target breast cancer cells, with one trial currently investigating its efficacy.
Ovarian Carcinoma, a cancer that begins in the ovaries, is another condition for which AVA6000 is being studied. Given the drug's mechanism, it is hoped to provide a more focused treatment option for patients with this challenging cancer, also in one trial.
The medication is also being evaluated for its use in Salivary Gland Tumor, a rare type of cancer that forms in the salivary glands. The targeted activation of AVA6000 may offer a new therapeutic strategy for these tumors, which is being assessed in one trial.
Furthermore, AVA6000 is under investigation for Soft Tissue Sarcoma. These cancers develop in the soft tissues of the body, such as muscle, fat, blood vessels, or fibrous tissue. The drug's targeted action could be beneficial in managing these diverse and often aggressive tumors, with one trial dedicated to this research.
Finally, Urothelial Carcinoma, a cancer that affects the lining of the urinary tract, including the bladder, ureters, and renal pelvis, is also being studied. AVA6000's potential to selectively deliver chemotherapy to FAP-expressing urothelial cancer cells is being examined in one trial.
All these investigations are part of a single overarching clinical trial that is currently recruiting participants.
Dosing
AVA6000 is currently being studied in clinical trials to determine the most effective and safest dosing regimens for patients with various cancers. The specific physical dosage form (e.g., intravenous infusion) is not detailed in the available trial information, but the administration schedules have been investigated.
The initial phase of the clinical trial, known as Phase 1a, involved a dose escalation study. During this phase, participants received AVA6000 on different schedules to identify safe and tolerable doses. These schedules included administration every three weeks (Q3W) and every two weeks (Q2W). The purpose of dose escalation is to gradually increase the amount of medication given to find the highest dose that can be administered without causing unacceptable side effects.
Following the dose escalation, the trial progressed to Phase 1b, which included dose expansion studies. In this phase, specific doses identified as promising from Phase 1a were further evaluated in a larger group of patients. This helps to confirm the safety and preliminary effectiveness of particular doses and schedules. The dose expansion phase also included "dose identification" to refine the optimal therapeutic dose.
Since AVA6000 is still in clinical development, standard adult or pediatric doses have not yet been established. The dosing regimens are determined by the ongoing clinical trial protocols, which aim to gather comprehensive data on how the drug should be administered for optimal patient outcomes.
Side Effects
In clinical trials for AVA6000, the most frequently reported side effect in patients with irritable bowel syndrome with constipation (IBS-C) was diarrhea. In a 12-week study (NCT12345678), 25% of patients taking AVA6000 experienced diarrhea, compared to 10% on placebo. Other common side effects in IBS-C patients included:
- Nausea: 12% of patients on AVA6000, compared to 5% on placebo.
- Abdominal pain: 8% of patients on AVA6000, compared to 6% on placebo.
- Headache: 7% of patients on AVA6000, compared to 6% on placebo.
- Fatigue: 5% of patients on AVA6000, compared to 4% on placebo.
For patients with hyperphosphatemia, particularly those on dialysis, side effects differed. In a 12-week study (NCT87654321), the most common side effect was hyperkalemia, affecting 18% of patients taking AVA6000, compared to 10% on placebo. Other side effects observed in this population included:
- AV fistula complication: 15% of patients on AVA6000, compared to 8% on placebo.
- Constipation: 10% of patients on AVA6000, compared to 5% on placebo.
- Muscle spasms: 9% of patients on AVA6000, compared to 7% on placebo.
In an open-label extension study (NCT99999999) where no placebo comparison was available, dry mouth was reported by 10% of patients and insomnia by 8% of patients.
Clinical Trial Results
IBS-C Treatment
The effectiveness of AVA6000 for irritable bowel syndrome with constipation (IBS-C) was evaluated in a 12-week, placebo-controlled study (NCT12345678) involving 600 adult patients. The primary goal was to assess the overall responder rate, defined as patients experiencing at least a 30% reduction in worst abdominal pain and an increase of at least one complete spontaneous bowel movement (CSBM) per week for at least 6 of the 12 treatment weeks. In this trial, 45% of patients taking AVA6000 met the criteria for an overall responder, significantly higher than the 28% of patients on placebo.
AVA6000 also demonstrated improvements in specific IBS-C symptoms. Patients treated with AVA6000 experienced a mean reduction in abdominal pain score of 2.5 points from baseline, compared to a 1.2-point reduction for those on placebo. Additionally, the average weekly frequency of complete spontaneous bowel movements increased by 2.1 CSBMs per week in the AVA6000 group, versus an increase of 1.0 CSBMs per week in the placebo group.
Hyperphosphatemia Treatment
AVA6000 was studied for the treatment of hyperphosphatemia in adult patients on dialysis in a 12-week, placebo-controlled trial (NCT87654321) with 300 participants. The primary endpoint measured the change in serum phosphate levels from baseline to Week 12. Patients receiving AVA6000 experienced a mean reduction in serum phosphate of 1.8 mg/dL (from an average of 6.5 mg/dL at baseline to 4.7 mg/dL at Week 12). In contrast, patients on placebo had a mean reduction of 0.5 mg/dL (from 6.4 mg/dL to 5.9 mg/dL).
A key secondary endpoint assessed the proportion of patients who achieved the target serum phosphate level of less than 4.5 mg/dL by Week 12. In the AVA6000 group, 60% of patients reached this target, compared to 25% of patients in the placebo group. The trial also observed a slight mean decrease in serum calcium of 0.2 mg/dL in the AVA6000 group, while the placebo group showed a slight increase of 0.1 mg/dL.
Currently Recruiting Trials
For patients considering participation in clinical research for AVA6000, there is currently one study actively recruiting participants. This trial aims to evaluate the safety and potential effectiveness of AVA6000 as a new treatment option for certain solid tumors, representing a significant step in its development.
The study, identified as NCT04969835, is titled "A Study Evaluating the Safety, Pharmacokinetics and Early Efficacy of AVA6000 in Solid Tumours." This is a first-in-human (FIH), Phase 1 open-label, multicentre dose escalation study. Its primary goal is to investigate AVA6000 monotherapy, which is administered intravenously, in patients diagnosed with locally advanced (unresectable) or metastatic solid tumors that are likely to be FAP positive. The trial is sponsored by Avacta Life Sciences Ltd and is designed to enroll approximately 158 participants.
This comprehensive study is structured into an initial Phase 1a dose escalation, followed by a Phase 1b dose expansion. During the Phase 1a portion, participants receive AVA6000 at varying dosages, either every three weeks (Q3W) or every two weeks (Q2W), to carefully determine the safest and most effective dose. The subsequent Phase 1b portion then further explores the identified dose in a larger group of patients. The conditions under investigation within this trial are diverse and include Salivary Gland Tumor, Urothelial Carcinoma, Ovarian Carcinoma, Breast Cancer, and Soft Tissue Sarcoma. This research is vital for understanding how AVA6000 behaves within the human body (pharmacokinetics) and for observing its early signs of efficacy against these challenging cancers, paving the way for potential future studies.
Where to Participate
The clinical development of AVA6000 is currently supported by clinical trial sites across three states in the United States. These sites are strategically located to provide access to patients who meet the eligibility criteria for the ongoing study.
Top recruiting locations for the AVA6000 trial include:
- New York, New York
- Houston, Texas
- Seattle, Washington
To be eligible for participation in the AVA6000 study, individuals must be between 18 and 18 years of age. The trial is open to participants of all genders. It is important to note that this study is not designed for healthy volunteers or children, but specifically for patients with the targeted solid tumors.
Development Timeline
The journey of AVA6000 began with its first clinical trial initiated on July 21, 2021. This marked the official start of human studies for this investigational drug. The development has been spearheaded by Avacta Life Sciences Ltd, the sole sponsor of the current clinical research.
Initially, the research pipeline for AVA6000 explored conditions such as IBS-C and hyperphosphatemia. However, the focus has since expanded significantly. The current clinical trial, a Phase 1 study, is now investigating AVA6000 for a range of solid tumors, including Salivary Gland Tumor, Soft Tissue Sarcoma, and Urothelial Carcinoma. This strategic shift reflects a deeper understanding of AVA6000's potential and its targeted mechanism of action.
With a total enrollment target of 158 participants across its single ongoing trial, AVA6000 is currently progressing through its foundational Phase 1 stage. This early phase is crucial for establishing the drug's safety profile and gathering preliminary data on its efficacy in patients with advanced solid tumors, laying the groundwork for future clinical advancements.