A Phase 2 study to evaluate the safety and tolerability of ACT001 in treating adults with Progressing Fibrosing Interstitial Lung Disease (PF-ILD), including Idiopathic Pulmonary Fibrosis (IPF)
A Phase 2 prospective multi-centre, parallel group study to evaluate the safety, tolerability, and activity of ACT001 in Adult participants with Progressing Fibrosing Interstitial Lung Disease (PF-ILD), including Idiopathic Pulmonary Fibrosis (IPF) when used alone or in combination with standard of care therapy.
Accendatech Au Pty Ltd
40 participants
Jul 29, 2020
Interventional
Conditions
Summary
The current treatment options for patients with progressing Fibrosing Interstitial Lung Disease (PF-ILD), including Idiopathic Pulmonary Fibrosis (IPF) is limited and specific cohorts of patients cannot tolerate the approved treatments. Following the demonstration of activity in animal models for respiratory fibrotic diseases, this study will evaluate the safety and biological activity of ACT001 in adult patients. The study design will utilise a daily dose of ACT001, either alone or in combination with standard of care anti-fibrotic therapy, with evaluate safety, anti-inflammatory and anti-fibrotic activity in patients with stable disease state and evaluate any change in their respiratory function of a 12 month treatment period. The outcomes of this study are intended to support the biological activity of ACT001 so as to provide outcomes that can be translated into future research.
Eligibility
Inclusion Criteria42
- Adult patients aged = 18 years at Consent
- Fibrosing lung disease on high resolution computerized tomography (HRCT), defined
- as reticular abnormality with traction bronchiectasis with or without honeycombing,
- with disease extent of over 10%, performed within 12 months of Visit 1. If the HRCT is
- outside of the 12 months window, a scan needs to be performed during Screening and
- prior to Visit 2 to confirm the diagnosis.
- For participants with underlying Connective Tissue Disease (CTD): stable CTD not
- requiring initiation of new therapy. If the patient has a pulmonary fibrosis component
- as part of the CTD and is progressing, this patient can be included.
- Pulmonary function at baseline reporting FVC of greater than 45% and DLCO of greater than 30%
- Able to complete home based spirometry reading as determined by investigator
- Female participants are eligible if they are of. Non-childbearing potential, defined as
- i. Previous hysterectomy or bilateral oophorectomy
- ii. Previous bilateral tubal ligation
- iii. Post-menopausal (total cessation of menses for greater than or equal to 1 year)
- d. Childbearing potential with a negative urine pregnancy test at screening, prior
- to investigational product administration, and uses highly effective
- contraception 28 days prior to commencement of study drug and throughout
- the study until 3 months after the last investigational product administration.
- Highly effective contraception, when used consistently and in accordance with
- both the product label and the instructions of the physician, are defined as
- follows:
- i. Vasectomized partner who is sterile prior to the female patient’s
- enrolment and is her sole sexual partner
- ii. An intrauterine device (IUD) with a documented failure rate of less
- than 1% per year (i.e. Copper or hormone-releasing IUD)
- iii. Double barrier contraception defined as condom with a female
- diaphragm
- iv. Combined (estrogen and progestogen containing) hormonal
- contraception associated with inhibition of ovulation and a barrier
- method
- v. Progestogen-only hormonal contraception associated with inhibition of
- ovulation and a barrier method
- vi. Sexual abstinence or in same sex relationship
- For men and women, acceptable methods of contraception include use of a condom
- with spermicide or use of oral, implantable or injectable contraceptives, or IUD or a
- diaphragm with spermicide or diaphragm with condom.
- Male participants with a potentially fertile partner are eligible if they have had a
- vasectomy or are willing to use adequate contraception 28 days prior to
- commencement of study drug administration and throughout the study until 3 months
- after the last investigational product administration. Female partners of male
- participants are advised to also use contraception as noted above.
Exclusion Criteria30
- History of chronic pulmonary obstructive disease that requires treatment, severe
- pulmonary hypertension, drug-induced pulmonary toxicity, other forms of
- idiopathic pneumonia, or interstitial lung diseases associated with environmental
- exposure medication or systemic disease. Should the Investigator feel that a patient
- would be suitable for inclusion into the study, but have components of their disease that fit into the above description, they should discuss this with the study Medical
- Monitor for consideration.
- Pre-existing hypersensitivity to ACT001 or related compounds
- Major extrapulmonary physiological restriction
- Cardiovascular diseases as determined by the investigator to be sufficient to exclude
- from participation, such as severe hypertension, myocardial infarction within 6
- months prior or unstable cardiac angina within 6 months
- Creatinine clearance <30mL/min calculated per the Cockcroft-gault equation
- Hepatic impairment as defined as AST or ALT >1.5 x upper limit of normal (ULN)
- with or without elevated bilirubin > 1.5 x ULN
- History of thrombotic event (including stroke and transient ischemic attack) within
- months
- Other disease that may interfere with testing procedures or in the judgment of the
- Investigator may interfere with trial participation or may put the patient at risk when
- participating in this study
- Women of childbearing potential not willing or able to use highly effective methods
- of birth control that result in a low failure rate of less than 1% per year when used
- consistently and correctly, as well as one barrier method for 28 days prior to and 3
- months after ACT001 administration. Male participants are also required to use
- suitable contraception for 28 days prior to and 3 months after last ACT001
- administration.
- Current use of other investigational agents
- Commencement or alteration of immune suppression or anti-fibrotic dosing within
- months of screening. If a patient requires a short course of steroids that is NOT
- for the purpose of immune suppression, this should be discussed with the study
- Medical Monitor as it may be appropriate to still include the patient.
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Interventions
The investigational product is ACT001, dimethylamino michael adduct of micheliolide (DMAMCL), the drug product is an immediate release capsule containing 100mg of DMAMCL and is yellow and grey in colour. Each size 0 capsule also contains gelatine starch, magnesium stearate and silicon dioxide. Using a three-step synthetic sequence, ACT001 was obtained from parthenolide, which can be isolated from western medical herb tanacetum parthenium (feverfew), or Chinese medical herb magnolia delavayi franch. Cohort 1 will recruit participants that have been diagnosed with pulmonary fibrosing interstitial lung disease (PF-ILD), and are not receiving antifibrotic therapy. Cohort 2 will recruit participants that have been diagnosed with PF-ILD, and are currently receiving antifibrotic therapy. Patients will be assigned after consent to be administered either ACT001 orally (400mg/day) alone, or in combination with existing antifibrotic treatments. Each oral daily dose will be taken as two capsules in the morning and two in the evening after meal, with each dose recorded, for up to 52 weeks at investigator's discretion based on clinical assessment of safe use. Participants will be required to return any unused doses of study drug and/or the original container to site. The number of capsules of study product returned to the site will be counted and recorded as a measure of compliance. The investigator must account for all used Investigational Product containers. The completed dispending and inventory record will be provided to the sponsor and copies filed in the Investigator Site File (ISF). At the completion or termination of the study, a final drug accountability review and reconciliation must be completed, and any discrepancies must be investigated, and their resolution documented.
Locations(1)
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ACTRN12619001643167