Phase 1 study of KCMC-001 for multidrug-resistant pulmonary tuberculosis resistant to chemotherapeutic agents INH and RFP

JRCT ID: jRCT2053190023

Registered date:31/05/2019

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Intractable pulmonary tuberculosis such as multidrug-resistant tuberculosis resistant to INH and RFP
• Date of first enrollment: 27/11/2019
• Target sample size: 6
• Study type: Interventional
• Intervention(s): A total of 18 weeks of trials, KCMC-001 (HVJ-E / HSP65 DNA + IL-12 DNA vaccine) is administered intramuscularly three times in two weeks using a syringe and then a 16 week observation period (drug withdrawal period) follows.

Outcome(s)

Primary Outcome

Evaluation of safety / tolerability
1. Presence or absence of adverse event, AE term, severity, expression frequency and expression period (CTCAE v4.0)
2.pVAX / HSP65 DNA + human IL-12 DNA (plasmid DNA) concentration in blood (qPCR )
3. IL-12 concentration in blood (EIA or ELISA)
4. Anti-HVJ-E antibody titer (HI) in blood
5. Anti-DNA antibody (anti-single strand DNA antibody and anti-double strand DNA antibody) in blood

Secondary Outcome

Preliminary assessment of effectiveness
Evaluation of anti-tuberculosis effect (1. bacteria count, 2. diagnostic imaging, 3. symptoms (cough, sputum, fever), 4 .ESR (red precipitate))
Evaluation of tuberculosis immunity induction ability (1. cell-mediated immunity induction to HSP65 and PPD antigen or H37Ra dead tuberculosis antigen (ELISPOT or ELISA using expression of IL-2 and IFN-gamma protein as index), 2. NK cell activity)

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: <= 90age old
• Gender: Both

Include criteria

1) Patients who give written consent of its free will to join the study
2) Patients who are not younger than 20 and not older than 90 when the consent obtained
3) Patients diagnosed as multidrug resistant pulmonary tuberculosis who do not respond to treatment by multiple chemotherapies or cannot continue the chemotherapies (WHO definition : resistant to both of INH and RFP) and no other recommended treatments can be selected. Or (1)tuberculosis patients to whom both of INH and RFP cannot be administered due to resistance or side effects, or (2)tuberculosis patients to whom RFP cannot be administered due to resistance or side effects and the risk of treatment failure is high due to there are 3 or less drugs that can be administered, and no other recommended treatments can be selected.
4) Patients with multidrug resistant pulmonary tuberculosis from whose clinical respiratory specimen culture (sputum, bronchoscope specimen, gastric juice) mycobacterium tuberculosis resistant to both of INH and RFP is detected within 6 months before the registration and continue to culture positive at the registration. (Being positive in culture within 60 days of registration)
Or (1)tuberculosis patients to whom both of INH and RFP cannot be administered due to resistance or side effects, or (2)tuberculosis patients to whom RFP cannot be administered due to resistance or side effects, and the risk of treatment failure is high due to there are 3 or less drugs that can be administered, and no other recommended treatments can be selected, from whose clinical respiratory specimen culture (sputum, bronchoscope specimen, gastric juice) mycobacterium tuberculosis is detected within 6 months before the registration and continue to culture positive at the registration. (Being positive in culture within 60 days of registration)
5) Patients whose PaO2 is not less than 70 mmHg or SpO2 is not less than 93 percent on room air
6) Patients who are expected to live for 22 weeks or longer after the consent obtained
7) Patients who have pulmonary lesions assessable by chest X-ray test or CT before the registration
8) Patients whose functions of bone marrow, liver and kidney are not worse as follows at the screening test
a. White blood cell : not less than 3,000 /micro L
b. Neutrophil : not less than 1,500 /micro L
c. Platelet : not less than 75,000 /micro L
d. Hemoglobin : not less than 8.0 g/dL
e. AST : not more than 100 IU/L
f. ALT : not more than 100 IU/L
g. Total bilirubin : not more than 2.5 mg/dL
h. Serum creatinine : not more than 2.5 mg/dL

Exclude criteria

1) Patients who show positive to the skin prick test with HVJ-E
2) Patients who have serious complication diseases such as uncontrolled active infections other than tuberculosis
3) Patients treated with immunotherapies within 4 weeks before the consent obtained
4) Patients who have active autoimmune diseases
5) Patients who are treated with systemic corticosteroids which suppress immune reactions
6) Patients who have medical history of auto or allogeneic organ or tissue transplantation and treated with systemic immunosuppressants when the consent obtained
7) Patients whose PT (percent) is more than 10 percent less of the lower limit of the hospital standard or whose APTT is more than 1.5 times over the upper limit of the hospital standard
8) Patients who are pregnant or lactating, or plan to get pregnant during the study period (Patients who stop lactating from the time giving consent to 30 days after the end of administration of the study product can join the study. Women of childbearing potential need to be tested for pregnancy with the urine beta HCG test.)
9) Patients who show positive results by HBs antigen, HCV antibody or HIV test at the screening test
10) Patients judged not to have abilities to give the consent due to psychiatric disorders or cognitive function declining
11) Patients diagnosed as immunodeficiency in the past
12) Patients who joined other clinical trials within 4 months before the consent obtained
13) Patients treated with blood transfusion or blood products such as gamma-globulin therapy within 3 months before the consent obtained or treated with high-dose gamma-globulin therapy within 6 months before the consent obtained
14) Patients administered BCG vaccine within one year before the consent obtained
15) Patients with a past medical history of severe anaphylactic shock, or patients who may have a severe life-threatening allergic or anaphylactic reaction.
16) Patients judged by physician in charge not appropriate to join the study

Related Information

• Primary Sponsor: Tsuyuguchi Kazunari
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development (AMED)