Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Rintatolimod, Poly I: Poly C12U (Rintatolimod), poly I-poly C12U, Rintatolimod (poly I : poly C12U), Atvogen
Ampligen · 8 trials · 24 indications
Proportion of patients in the safety cohort (chemoimmunotherapy combined with the αDC1 vaccine) experiencing a dose-limiting toxicity (DLT). A DLT will be any adverse event that is at least possibly related to the study treatment and prevents surgery or delays surgery by more than 4 weeks, or that prevents the initiation of the next cycle of treatment on schedule due to toxicity in the prior cycle. The DLT period will be 2 cycles of treatment.
Percentage of patients who show no detectable cancer (cells) in tissue samples after neoadjuvant treatment as assessed at the time of the interval debulking procedure. Per RECIST v1.1, Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in SLD compared to baseline, confirmed on a follow-up scan.
Change in mean fatigue T-score as measured by PROMIS® (Patient-Reported Outcomes Measurement Information System) Fatigue short form 7a that assess a range of self-reported symptoms, from mild subjective feelings of tiredness to extreme exhaustion. The lowest possible raw score is 7; the highest possible raw score is 35. Raw summed scores are converted to T-score values that are standardized such that 50 represents the average (mean) for the US general population, with a standard deviation of 10 points. The lowest possible T-score is 29.4; the highest possible T-score is 83.2. A higher T-score represents more of the concept being measured, meaning the higher the T-Score, the worse the fatigue of the individual. Scores \<55 are within normal limits, 55-60 mild, 61-70 moderate, and \>70 severe fatigue.
This will be assessed by the increase in the total number of tumor infiltrating CD8+ T cells in the radical prostatectomy specimen (measured as cell density of CD8+ cell by immunohistochemistry), comparing Arm A versus Arm B versus Arm C. Will be natural log transformed prior to analysis. The primary analysis will consist of testing the single degree of freedom planned contrast at alpha = .10 that the 3 treatment means are in the ratio of 3:2:1 (contrast coefficients 3, -2, -1) for groups A, B and C, respectively groups. If this test rejects the null hypothesis of no group differences, will proceed to estimate group means and pairwise differences between groups with 90% confidence intervals. Non-overlapping confidence intervals will serve as evidence of differential treatment effects.
To evaluate the potential effectiveness of Ampligen to increase the HAART-free time interval before HIV rebound during the STI of HAART.
The primary endpoint of the safety run-in (phase Ib) is the recommended phase II dose (RP2D) defined by the highest dose per protocol without dose-limiting toxicity (DLT) according to a 3+3 design related to the intervention. A DLT is defined as the occurrence of an adverse event (AE) that is at least possibly related to the investigational product (IP) or investigational regimen (IR), with two exceptions: any grade of vitiligo or alopecia will not qualify as a DLT. The DLT assessment period is from the time of first dose of IP/IR and ends upon administration of the first dose of IP/IR on Cycle 2, Day 1 (28 day cycle). Toxicities will be scored according to CTC criteria version 5.0 (Published November 27th, 2017). All participants that cannot complete the combination therapy as planned due to directly related toxicity will be discussed in the Study Steering Committee and they will determine whether the patient is classified as having a DLT.
Response is defined as stable disease, partial or complete response according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1), determined 6 months after start of combination therapy. If the number of responses is ≥ 4 out of 25 patients further research of this treatment regime is justified. Furthermore, the lower boundary of the 90% CI should be higher than 5% to justify further research of this treatment regime.
The proportion of subjects with the best response of complete response (CR), or partial response (PR) per Response Evaluation Criteria for Solid Tumors (RECIST 1.1). Per RECIST 1.1 , CR is defined as all target lesions gone; PR is defined as a \> 30% decrease in size of lesion from baseline.
Will be assessed using a Simon two-stage minimax design.
| Arm | Type | Description |
|---|---|---|
| Safety Lead-in: Paclitaxel + Cisplatin + Bioferon + Rintatolimod + Pembrolizomab + Celecoxib | EXPERIMENTAL | - |
| Paclitaxel + Cisplatin + Bioferon + Rintatolimod + DC1 Vaccine + Pembrolizomab + Celecoxib | EXPERIMENTAL | - |
| Ampligen / rintatolimod | EXPERIMENTAL | Subjects will receive rintatolimod (intravenous \[IV\]), up to 400 mg twice weekly for 12 weeks. |
| Placebo / Saline | PLACEBO_COMPARATOR | Subjects will receive placebo / normal saline (intravenous \[IV\]), up to 160 mL twice weekly for 12 weeks. |
| Arm I (EC aspirin, interferon alpha, rintatolimod, surgery) | EXPERIMENTAL | Patients receive aspirin PO BID on days -7 to 7. Patients also receive recombinant interferon alfa-2b IV over 20 minutes and rintatolimod IV over 2 hours on days 1-3 and 8-10 in the absence of disease progression or unacceptable toxicity. Patients then undergo radical prostatectomy on or between day 17-24.. |
| Arm II (EC aspirin, rintatolimod, surgery) | EXPERIMENTAL | Patients receive aspirin PO BID on days -7 to 7 and rintatolimod IV over 2 hours on days 1-3,and 8-10 in the absence of disease progression or unacceptable toxicity. Patients then undergo radical prostatectomy on or between day 17-24. |
| Arm III (radical prostatectomy) | ACTIVE_COMPARATOR | Patients undergo radical prostatectomy about 4 weeks after enrollment. |
| Ampligen | EXPERIMENTAL | Ampligen (poly I-poly C12U) 200-400 mg IV infusions given twice weekly for 64 weeks. |
| No Ampligen | NO_INTERVENTION | No Ampligen administered for first 64 weeks |
| Durvalumab and rintatolimod combination therapy | EXPERIMENTAL | 1500mg Durvalumab administered via IV infusion once every first day of a 28 day cycle for a total of maximum 12 cycles (12 infusions in total). 200-400mg Rintatolimod administered via IV infusion twice per week for a total of 6 weeks (12 infusions in total). |
| cisplatin + rintatolimod + pembrolizumab | EXPERIMENTAL | Intraperitoneal (IP) cisplatin 50mg/m\^2 solution with IP rintatolimod 200 mg solution and IV pembrolizumab 200 mg solution. |
| Treatment (chemokine modulation therapy) | EXPERIMENTAL | Participants undergo pre-treatment biopsy. Participants then undergo chemokine modulation therapy consisting of celecoxib PO BID, recombinant interferon alfa-2b IV over 20 minutes, and rintatolimod IV over 30-60 minutes on days -11 to -9, and -4 to -2. Participants then undergo additional biopsy. Following biopsy and chemokine modulation therapy, participants receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. |
| Name | Type | Description |
|---|---|---|
| Ampligen | DRUG | - |
| Paclitaxel | DRUG | A chemotherapy for cancer patients that interferes structures that help move chromosomes during cell division, thus stabilizing these structures to prevents cancer cells from dividing and ultimately causing them to die. Dose: 175 mg/m\^2 IV on D1 each cycle during neoadjuvant and adjuvant periods. |
| Cisplatin | DRUG | An alkylating agent that contains platinum, which binds to DNA in cancer cells, causing cross-links that prevent DNA replication and repair, leading to cell death, particularly in rapidly dividing cancer cells. Dose: 75 mg/m\^2 IP / 1 hour on D1 of each cycle during neoadjuvant and adjuvant treatment periods. |
| Bioferon | DRUG | Inhibits replication of a wide range of RNA and DNA viruses and exerts antiproliferative effects on malignant cells. It suppresses antibody formation through an effect on B-lymphocytes and inhibits onset of delayed hypersensitivity. Dose:6 milli on units/100 mL IP over 30-60 minutes on D2 of each cycle during neoadjuvant and adjuvant treatment. D1 during maintenance treatment periods. |
| Rintatolimod | DRUG | A synthetic double-stranded RNA that selectively activates Toll-like Receptor 3 (TLR3), triggering antiviral and immunomodulatory responses, priming the immune system without causing excessive inflammation. Dose: 200 mg IP over 1-2 hours on D2 of each cycle during the neoadjuvant and adjuvant treatment periods. D1 during maintenance treatment periods |
| αDC1 Vaccine | BIOLOGICAL | Autologous tumor-loaded alpha-DC1 vaccine is the new type of dendritic cell vaccine developed by our group, are the serum-free, clinically-applicable version of type-1 polarized DCs, combining a fully-mature phenotype and high expression of co-stimulatory molecules with an elevated, rather than exhausted, ability to produce IL-12p70. Dose: 6 million dendritic cells (reduced or omitted if insufficient vaccine material), ID injection on rotating sides of lower extremities on D2 each cycle during the neoadjuvant (not C1) and adjuvant treatment periods. D1 of each cycle during maintenance period. |
| Pembrolizumab | DRUG | Humanized monoclonal antibody and a PD-1 inhibitor used in cancer immunotherapy that differs from chemotherapy as it does not directly kill cancer cells but stimulates the immune system, particularly T-cells, to recognize and attack cancer cells more effectively. Dose: 200 mg IV / 30 minutes on D2 of each cycle during neoadjuvant treatment period (none last neoadjuvant cycle), then optional on D2 for adjuvant treatment cycles, and on D1 of maintenance cycles |
| Celecoxib | DRUG | A COX-2 inhibitor in the class of nonsteroidal anti-inflammatory drugs (NSAIDs) that specifically target the cyclooxygenase-2 (COX-2) enzyme, which plays a key role in inflammation Dose: 200mg/day, orally twice a day for days 1-5 and once a day for days 6-21 of neoadjuvant and adjuvant treatment cycles, and then twice a day on D1 and once a day for days 2-21 for maintenance cycles |
| Debulking Procedure | PROCEDURE | A surgical procedure designed to remove the majority of cancerous tumors when complete removal may not be feasible, with the goal of reducing tumor burden, making follow-up treatments like chemotherapy or radiation more effective. Surgery occurs in between the neoadjuvant and adjuvant treatment periods. |
| Placebo / Normal Saline | OTHER | 40 to 160 mL twice weekly |
| EC Aspirin | DRUG | Given PO |
| Radical Prostatectomy | PROCEDURE | Undergo radical prostatectomy |
| Recombinant Interferon Alfa-2b | BIOLOGICAL | Given IV |
| poly I-poly C12U | DRUG | 200-400 mg IV infusions 2x/week for 64 weeks |
| Durvalumab | BIOLOGICAL | Human anti-PD-L1 antibody |
| Biopsy | PROCEDURE | Undergo Biopsy |
| Chemokine Modulation Therapy | PROCEDURE | Undergo chemokine modulation therapy |
Inclusion Criteria: 1. A diagnosis of CFS, as defined by the Center for Disease Control (1988 CDC case definition) \> 12 months (Appendix D). 2. Age Range: \> 18 years old, \< 60 years old. 3. Males or non-pregnant, non-lactating females: Females must be of non-child bearing potential (either post-...
Ampligen is being studied for the treatment of Chronic Fatigue Syndrome, also known as Myalgic Encephalomyelitis. It is an investigational small molecule developed by AIM ImmunoTech Inc. for this neurological condition. The clinical program has focused on evaluating its safety and efficacy in adults with this illness.
Ampligen is developed by AIM ImmunoTech Inc., which trades under the ticker AIM. The company is responsible for the clinical development of this investigational small molecule for Chronic Fatigue Syndrome and related conditions.
Ampligen is in Phase 3 clinical development for Chronic Fatigue Syndrome. It is an investigational therapy and has not been approved by the FDA for this indication. The Phase 3 program has been completed, and further regulatory steps would be required before any potential approval.
Ampligen has been evaluated in a Phase 3 trial, NCT00215800, titled The Study of the Safety and Efficacy of Ampligen in Chronic Fatigue Syndrome. This completed trial enrolled 234 participants with Chronic Fatigue Syndrome and Myalgic Encephalomyelitis. It was a randomized, double-blind study that included adults aged 18 years and older.
Ampligen is not FDA approved for Chronic Fatigue Syndrome. It remains an investigational small molecule in Phase 3 clinical development by AIM ImmunoTech Inc. The completed Phase 3 trial, NCT00215800, evaluated its safety and efficacy, but no approval has been granted for this indication.