Euphorbia Kansui and HIV/AIDS Functional Cure

NCT04503928 | Unknown Phase 1

• 1 other identifier: Euphorbia kansui V1
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the safety and bioactivity of Euphorbia kansui, which has been used in traditional Chinese medicine for the treatment of edema, ascites, and asthma. The investigators previously reported that effective fractions from the dichloromethane extracts of the roots of Euphorbia kansui can reactivate latent HIV-1 replication in different latent cells (The 24th China science technology Forum-High level Forum on HIV cure, December 16-17, 2012, Beijing). Importantly, in resting CD4+ T cells of HIV-1-infected patients on suppressive antiretroviral therapy (ART), it could effectively induce ex vivo latent HIV-1 expression. Sera from rats receiving orally administered effective fractions were able to reactivate latent HIV-1. The investigators also found a substantially potent ingenol derivative EK-16A, EK-1A, EK-5A, EK-15A from Euphorbia kansui and proved that it was potent in reversing HIV-1 latency. The investigators' hypothesis is that Euphorbia kansui Pill will be safe and well-tolerated and at the doses administered, increase HIV transcription in latently-infected cells among HIV-infected patients on suppressive antiretroviral therapy.

Conditions

HIV-1-infection

Outcome Measures

Primary Outcomes (3)

• Change in plasma HIV-1 RNA concentration

  Measured on day 0; 1, 3, 5, 7 (12 hours post administration); 14, 21.

• Change in cell-associated HIV-1 RNA

  on day 0; 1, 3, 5, 7 (12 hours post administration); 14, 21

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  Measured through 21 days after the first administration of kansui Pill

Secondary Outcomes (1)

• Change in cell-associated total HIV-1 DNA

  Measured on day 0, 14, 21

Study Arms (1)

Experimental: Kansui 1g per day x 7 days

EXPERIMENTAL

Study participants will be given 1 g of Euphorbia kansui Pill for a total of 7 consecutive daily doses.

Drug: Euphorbia kansui Pill

Interventions

Euphorbia kansui Pill DRUG

1 g (10 pills) of Euphorbia kansui Pill taken by mouth, once a day for 7 consecutive days.

Also known as: kansui

Experimental: Kansui 1g per day x 7 days

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV-1 infection
• Age ≥18 years; Willingness to give written informed consent.
• Karnofsky performance status \>70.
• Able, willing to adhere to therapy and adherent to ART.
• Able, willing to comply with time requirements for study visits and evaluations.
• On potent combination ART for ≥ 18 months prior to study entry.
• Able to swallow pills without difficulty.
• HIV-1 RNA values \<50 copies/mL for at least 18 months.
• CD4 cell count ≥ 500 cells/µl at screening.
• CD4 T cells isolated in vitro and stimulated with kansui, and the kansui activation test is positive.
• All volunteers must agree not to participate in a conception process.
• Must have adequate organ function as indicated by the following lab values:
• Hematological: Absolute Neutrophil Count (ANC) ≥ 1,500/mcL Platelets ≥ 125,000/mcL Hgb ≥ 12 g/dL Coagulation: Prothrombin Time or International Normalized Ratio (INR) ≤ 1.5x upper limit of normal (ULN) Chemistry: K+ levels Within normal limits Mg++ levels \> Lower limits of normal (LLN) but \<1.5 x ULN Glucose Screening serum glucose(fasting/non-fasting) below 120 mg/dl.
• Renal: Serum creatinine/calculated creatinine clearance\* ≤ 1.3 X ULN OR ≥ 60 mL/min for participants with creatinine levels \> 1.3 X ULN Hepatic: Serum total bilirubin Total bilirubin \< 1.5 times ULN. If total bilirubin is elevated, direct bilirubin will be measured and the participant will be eligible if the direct bilirubin is \< 2 X ULN.
• Aspartate amino transferase (AST) (SGOT) and Alanine amino transferase (ALT) (SGPT)≤ 2.0 X ULN Lipase \<1.6 X ULN Alkaline Phosphatase ≤ 2.5 X ULN.

You may not qualify if:

• Acute HIV-1 infection
• Received blood transfusions or hematopoetic growth factors within 3 months
• Receipt of compounds with other latency activators within 1 month.
• Any significant acute medical illness in the past 8 weeks
• Hepatitis B or C infection as indicated by the presence of Hepatitis B surface antigen (HBsAg) or hepatitis C virus RNA (HCV-RNA) in blood
• Patient has the following laboratory values within 3 weeks before starting the investigational drug Hepatic transaminases (AST or ALT) ≥3 x upper limit of normal (ULN) Serum total bilirubin ≥1.5 ULN Serum creatinine levels ≥1.5 x ULN, or calculated creatinine clearance ≤60 ml/min Platelet count ≤100 x109/L Absolute neutrophil count ≤1.5x109/L Serum potassium, magnesium, phosphorus outside normal limits Total calcium (corrected for serum albumin) or ionized calcium ≤lower normal limits
• A personal history of clinically significant cardiac disease, symptomatic or asymptomatic arrhythmias, syncopal episodes, or additional risk factors for Torsades de pointes (e.g. heart failure)
• History of malignancy or transplantation, including skin cancers or Kaposi sarcoma
• History of diabetes mellitus
• Known hypersensitivity to Kansui
• Pregnancy or breast feeding, or expecting to father children within the projected duration of the study
• Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

Sponsors & Collaborators

• Shanghai Public Health Clinical Center: lead
• Fudan University: collaborator
• Shanghai Xinhao Biological Technology Co., Ltd.: collaborator

Study Sites (1)

Shanghai,China, Fudan University

Shanghai, China

Location

Related Publications (2)

• Wang P, Lu P, Qu X, Shen Y, Zeng H, Zhu X, Zhu Y, Li X, Wu H, Xu J, Lu H, Ma Z, Zhu H. Reactivation of HIV-1 from Latency by an Ingenol Derivative from Euphorbia Kansui. Sci Rep. 2017 Aug 25;7(1):9451. doi: 10.1038/s41598-017-07157-0.

  PMID: 28842560 BACKGROUND

• Yang H, Li X, Yang X, Lu P, Wang Y, Jiang Z, Pan H, Zhao L, Zhu Y, Khan IU, Shen Y, Lu H, Zhang T, Jiang G, Ma Z, Wu H, Zhu H. Dual effects of the novel ingenol derivatives on the acute and latent HIV-1 infections. Antiviral Res. 2019 Sep;169:104555. doi: 10.1016/j.antiviral.2019.104555. Epub 2019 Jul 9.

  PMID: 31295520 BACKGROUND

Related Links

• Related Info

Study Officials

• Hongzhou Lu, M.D.

  Shanghai Public Health Clinical Center

  PRINCIPAL INVESTIGATOR

• Huanzhang Zhu, M.D.

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Huanzhang Zhu, M.D.

CONTACT

31246728; hzzhu@fudan.edu.cn

Jingna Xun, MD

CONTACT

37990333; xunjingna@shphc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Open label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Model Details: All participants eligible for study received the same open label drug

Study Record Dates

• First Submitted: August 5, 2020
• First Posted: August 7, 2020
• Study Start: August 1, 2020
• Primary Completion: August 1, 2022
• Study Completion: December 1, 2022
• Last Updated: August 10, 2020

Record last verified: 2020-08

Locations

CN (1)