scholarly journals Long-term safety and efficacy of intramyocardial adenovirus-mediated VEGF-DΔNΔC gene therapy eight-year follow-up of phase I KAT301 study

Gene Therapy ◽  
2021 ◽  
Author(s):  
Aleksi J. Leikas ◽  
Iiro Hassinen ◽  
Antti Hedman ◽  
Antti Kivelä ◽  
Seppo Ylä-Herttuala ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Phase I ◽  
Myocardial Perfusion Reserve ◽  
Control Group ◽  
Cardiovascular Adverse Event ◽  
Safety And Efficacy ◽  
Perfusion Reserve ◽  
Canadian Cardiovascular Society Class

AbstractIn phase I KAT301 trial, intramyocardial adenovirus-mediated vascular endothelial growth factor -DΔNΔC (AdVEGF-D) gene therapy (GT) resulted in a significant improvement in myocardial perfusion reserve and relieved symptoms in refractory angina patients at 1-year follow-up without major safety concerns. We investigated the long-term safety and efficacy of AdVEGF-D GT. 30 patients (24 in VEGF-D group and 6 blinded, randomized controls) were followed for 8.2 years (range 6.3–10.4 years). Patients were interviewed for the current severity of symptoms (Canadian Cardiovascular Society class, CCS) and perceived benefit from GT. Medical records were reviewed to assess the incidence of major cardiovascular adverse event (MACE) and other predefined safety endpoints. MACE occurred in 15 patients in VEGF-D group and in five patients in control group (21.5 vs. 24.9 per 100 patient-years; hazard ratio 0.97; 95% confidence interval 0.36–2.63; P = 0.95). Mortality and new-onset comorbidity were similar between the groups. Angina symptoms (CCS) were less severe compared to baseline in VEGF-D group (1.9 vs. 2.9; P = 0.006) but not in control group (2.2 vs. 2.6; P = 0.414). Our study indicates that intramyocardial AdVEGF-D GT is safe in the long-term. In addition, the relief of symptoms remained significant during the follow-up.

scholarly journals Long-term safety and efficacy of intramyocardial adenovirus-mediated VEGF-DΔNΔC gene therapy: eight-year follow-up of phase 1 KAT301 study

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
A J Leikas ◽  
I Hassinen ◽  
A Hedman ◽  
A Kivela ◽  
S Yla-Herttuala ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Phase 1 ◽  
Myocardial Perfusion Reserve ◽  
University Hospital ◽  
Control Group ◽  
Safety And Efficacy ◽  
Funding Sources ◽  
Perfusion Reserve

Abstract Backgound/Introduction In phase I KAT301 trial, adenovirus-mediated intramyocardial vascular endothelial growth factor-DΔNΔC (VEGF-D) gene therapy (GT) resulted in a significant improvement in myocardial perfusion reserve and relieved angina at 1-year follow-up without major safety concerns. Purpose Our objective was to investigate the long-term safety and efficacy of AdVEGF-D GT. A total of 30 patients (24 VEGF-D and 6 randomized and blinded controls) participated in KAT301 trial. Methods The mean follow-up time was 8.2 years (range 6.3–10.4 years). Patients were interviewed for the current severity of symptoms (Canadian Cardiovascular Society class, CCS) and perceived benefit from GT. Medical records were reviewed to assess the incidence of major cardiovascular adverse events (MACEs) and other predefined endpoints including cancer. Results MACE occurred in 15 patients in VEGF-D group and in five patients in control group (21.5 vs. 24.9 per 100 patient-years; hazard ratio 0.90; 95% confidence interval 0.09–9.32; P=0.95). Mortality and comorbidity were similar between the groups. Angina symptoms (CCS) were less severe compared to baseline in VEGF-D group (1.9 vs. 2.9; P=0.006) but not in control group (2.2 vs. 2.6; P=0.414). Conclusion(s) Our study indicates that intramyocardial AdVEGF-D GT is safe in the long-term. In addition, the relief of symptoms remained significant during the follow-up. FUNDunding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Kuopio University Hospital Heart Center Figure 1. The incidence of MACE Figure 2. CCS class

scholarly journals Long-Term Follow-Up of a Phase I/II Study of ProSavin, a Lentiviral Vector Gene Therapy for Parkinson's Disease

2018 ◽  
Vol 29 (3) ◽  
pp. 148-155 ◽  
Author(s):  
Stéphane Palfi ◽  
Jean Marc Gurruchaga ◽  
Hélène Lepetit ◽  
Katy Howard ◽  
G. Scott Ralph ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Gene Therapy ◽  
Parkinson's Disease ◽  
Phase I ◽  
Lentiviral Vector ◽  
Long Term Follow Up

scholarly journals Update on Gene Therapy Clinical Trials for Choroideremia and Potential Experimental Therapies

Medicina ◽  
2021 ◽  
Vol 57 (1) ◽  
pp. 64
Author(s):  
Alessandro Abbouda ◽  
Filippo Avogaro ◽  
Mariya Moosajee ◽  
Enzo Maria Vingolo
Keyword(s):  
Gene Therapy ◽  
Clinical Trials ◽  
Phase I ◽  
Late Phase ◽  
Cell Types ◽  
Operative Management ◽  
Therapeutic Window ◽  
Experimental Therapies

Background and objectives: Choroideremia (CHM) is an X-linked recessive chorioretinal dystrophy caused by mutations involving the CHM gene. Gene therapy has entered late-phase clinical trials, although there have been variable results. This review gives a summary on the outcomes of phase I/II CHM gene therapy trials and describes other potential experimental therapies. Materials and Methods: A Medline (National Library of Medicine, Bethesda, MD, USA) search was performed to identify all articles describing gene therapy treatments available for CHM. Results: Five phase I/II clinical trials that reported subretinal injection of adeno-associated virus Rab escort protein 1 (AAV2.REP1) vector in CHM patients were included. The Oxford study (NCT01461213) included 14 patients; a median gain of 5.5 ± 6.8 SD (−6 min, 18 max) early treatment diabetic retinopathy study (ETDRS) letters was reported. The Tubingen study (NCT02671539) included six patients; only one patient had an improvement of 17 ETDRS letters. The Alberta study (NCT02077361) enrolled six patients, and it reported a minimal vision change, except for one patient who gained 15 ETDRS letters. Six patients were enrolled in the Miami trial (NCT02553135), which reported a median gain of 2 ± 4 SD (−1 min, 10 max) ETDRS letters. The Philadelphia study (NCT02341807) included 10 patients; best corrected visual acuity (BCVA) returned to baseline in all by one-year follow-up, but one patient had −17 ETDRS letters from baseline. Overall, 40 patients were enrolled in trials, and 34 had 2 years of follow-up, with a median gain of 1.5 ± 7.2 SD (−14 min, 18 max) in ETDRS letters. Conclusions: The primary endpoint, BCVA following gene therapy in CHM, showed a marginal improvement with variability between trials. Optimizing surgical technique and pre-, peri-, and post-operative management with immunosuppressants to minimize any adverse ocular inflammatory events could lead to reduced incidence of complications. The ideal therapeutic window needs to be addressed to ensure that the necessary cell types are adequately transduced, minimizing viral toxicity, to prolong long-term transgenic potential. Long-term efficacy will be addressed by ongoing studies.

scholarly journals Update on the safety and efficacy of retroviral gene therapy for immunodeficiency due to adenosine deaminase deficiency

Blood ◽  
2016 ◽  
Vol 128 (1) ◽  
pp. 45-54 ◽  
Author(s):  
Maria Pia Cicalese ◽  
Francesca Ferrua ◽  
Laura Castagnaro ◽  
Roberta Pajno ◽  
Federica Barzaghi ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Immune Reconstitution ◽  
Adenosine Deaminase Deficiency ◽  
Leukemic Transformation ◽  
Safety And Efficacy ◽  
Cd34 Cells ◽  
Key Points ◽  
Severe Infections

Key PointsSurvival was 100% for 18 patients with ADA-SCID treated with genetically modified CD34+ cells (2.3-13.4 years follow up; median, 6.9 years). Long-term engraftment, immune reconstitution, and fewer severe infections were observed in 15 out of 18 patients without leukemic transformation.

scholarly journals Results of 5-year follow-up study in patients with peripheral artery disease treated with PL-VEGF165 for intermittent claudication

2018 ◽  
Vol 12 (9) ◽  
pp. 237-246 ◽  
Author(s):  
Roman Deev ◽  
Igor Plaksa ◽  
Ilia Bozo ◽  
Nina Mzhavanadze ◽  
Igor Suchkov ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Treatment Group ◽  
Lower Limb ◽  
Limb Ischemia ◽  
Walking Distance ◽  
Lower Limb Ischemia ◽  
Safety And Efficacy ◽  
Follow Up Study

Background: The effective treatment of chronic lower limb ischemia is one of the most challenging issues confronting vascular surgeons. Current pharmacological therapies play an auxiliary role and cannot prevent disease progression, and new treatment methods are needed. In 2011, a plasmid VEGF65-gene therapy drug was approved in Russia for the treatment of chronic lower limb ischemia ( ClinicalTrials.gov identifier: NCT03068585). The objective of this follow-up study was to evaluate the long-term safety and efficacy of gene therapy in patients with limb ischemia of atherosclerotic genesis. Aims: To evaluate the long-term safety and efficacy of the therapeutic angiogenesis, 36 patients in the treatment group (pl- VEGF165) and 12 patients in the control group participated in a 5-year follow-up study. Planned examinations were carried out annually for 5 years after pl- VEGF165 administration. Results: Differences in the frequency of major cardiovascular events (pl- VEGF165 5/36 versus control 2/12; p = 0.85), malignancies (pl- VEGF165 1/36 versus control 0/12; p = 0.38) and impaired vision (there was none in either group) over the 5-year follow-up period did not achieve statistical significance. The target limb salvage was 95% ( n = 36) and 67% ( n = 12) in the pl- VEGF165 and control groups, respectively. The pain-free walking distance value increased by 288% from 105.7 ± 16.5 m to 384 ± 39 m in the treatment group by the end of the fifth year, with a peak of 410.6 ± 86.1 m achieved by the end of the third year. The ankle-brachial index (ABI) increased from 0.47 ± 0.01 to 0.56 ± 0.02 by the end of the first year, with a subsequent slight decrease to 0.51 ± 0.02 by the fifth year. The maximum increment of transcutaneous oximetry test (tcoO2) by 36%, from 66.6 ± 3.7 mm Hg to 90.7 ± 4.9 mm Hg, was observed by the end of the second year. Conclusion: The therapeutic effect of angiogenesis induction by gene therapy persists for 5 years.

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