Human Studies

Summary of most recent Phase I human clinical studies on Crotoxin

April 2018 — Phase 1 Cohort 1 and Phase 1 Cohort 2

Celtic Biotech Iowa, Inc., reported results from Cohort 1 and Cohort 2 of its Phase I Crotoxin clinical trial at the American Association for Cancer Research (AACR) 2018 Annual Meeting.

Results from Phase I Cohort 1, Innovative design for a phase I trial with intra-patient dose escalation: The Crotoxin study, indicated that intra-patient dose escalation can be achieved without any observed serious drug-related adverse effects. Additionally, patient pain impact questionnaires conducted concurrent with treatment suggested that Crotoxin provided analgesic activity. Results from Phase I Cohort 2, Continuous i.v. Crotoxin in advanced cancer: Intra-patient dose escalation, indicated that faster dose escalation was achievable. Evaluation of antitumor response showed that two of the six subjects had stable disease on Day 36.

Celtic Biotech Human StudiesPhase 1 Human Study Published in Clinical Cancer Research

Twenty-three patients were evaluated after the administration of crotoxin as a daily injection for 30 consecutive days. No significant toxicity or respiration impairment was observed, and injection site reactions and double vision were the most characteristic observed side effects. Four patients did not complete the trial for differing reasons and one patient had an anaphylactoid reaction and was removed from the protocol.

Eighteen out of the 23 patients reported a progressive decrease or disappearance of pain. The reduction in pain was also reflected by the decrease in consumption of analgesics. This effect was noted regardless of disease progression.

Regarding the efficacy of the drug, there was no disease progression observed in four patients and partial responses were observed in thee patients. Treatment with crotoxin in one patient reduced the size of a thyroid carcinoma tumor mass by ~88%. A patient with a rectal carcinoma showed an ~90% tumor mass reduction after treatment with crotoxin. A patient whose breast cancer with lung metastases and pleural effusion was treated with crotoxin presented a complete response in less than four months, without any weight loss, that lasted six months after suspension of the treatment.

J E Cura, D P Blanzaco, C B Brisson, M A Cura, R Cabrol, L Larrateguy, C Mendez, J C Sechi, J S Silveira, E Theiller, A R deRoodt and J C Vidal: Phase I and Pharmacokinetic study of Crotoxin (Cytotoxic PLA2, NSC-624244) in Patients with Advanced Cancer. Clinical Cancer Research, Vol. 8, 1033-1041 (2002)

Celtic Biotech Human StudiesPhase 1 Human Study Published in Immunopharmacol. Immunotoxicol.

The authors report their clinical experience with VRCTC-310 in two patients suffering with advanced cancer in which the skin was severely compromised. Local treatment with VRCTC-310 provoked the complete disappearance of a relapsed skin squamous cell cancer in one patient. The other patient was an aged woman with local-advanced breast cancer who was inoculated with VRCTC-310. After six weekly courses, a >80% tumor reduction was seen. A 133 days follow-up demonstrated a complete response of the primary tumor mass, the disappearance of supraclavicular tumor mass as well a significant reduction in lymphangitis.

Costa LA, Miles F, Araujo CE, Gonzalez S, and Villaruba VG: Tumor regression of advanced carcinoma following intra-and/or peri-tumoral inoculation with VRCTC310 in humans: preliminary report of two cases, Immunopharmacol. Immunotoxicol. 20 (1), 15-25 (1998)

Celtic Biotech Human StudiesPhase 1 Human Study Published in Anticancer Drugs

Phase I study performed to evaluate the maximum tolerated dose, safety profile and pharmacokinetic data with VRCTC-310. Fifteen patients with refractory malignancies were administered VRCTC-310 injections daily for 30 consecutive days with doses escalated from 0.0025 to 0.023 mg/kg. Toxicities included local pain at the injection site, eosinophilia, reversible diplopia and palpebral ptosis. Dose escalation was stopped at 0.023 mg/kg, when two patients had developed anaphylactoid reactions. Stabilization was found in six patients.

Costa LA, Miles F, Diez RA, Araujo CE, Coni Molina CM and Cervellino JC; Phase I study of VRCTC310, a purified phospholipase A2 purified from snake venom, in patients with refractory cancer: safety and pharmacokinetic data, Anticancer Drugs 8 (9), 829-34 (1997)

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