Clinical Trials Register

Summary
EudraCT Number:	2019-002414-40
Sponsor's Protocol Code Number:	CXA-10-2302
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2019-10-24
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2019-002414-40

A.3

Full title of the trial

A Phase 2, Multi-Center, Open-Label Study to Evaluate Long-term Safety and Efficacy of CXA-10 in Subjects with Pulmonary Arterial Hypertension on Stable Background Therapy: Extension to Study CXA-10-301.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

An extension study, at multiple study sites, for patients with Pulmonary Arterial Hypertension who took part in study CXA-10-301, to look at the continuing safety of CXA-10 and how well it works long term: all patients will receive CXA-10 treatment.

A.3.2

Name or abbreviated title of the trial where available

Open label extension of CXA-10 in Pulmonary Arterial Hypertension

A.4.1

Sponsor's protocol code number

CXA-10-2302

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT04053543

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Complexa Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Complexa Inc.
B.5.2	Functional name of contact point	Craig Pfister
B.5.3	Address:
B.5.3.1	Street Address	1055 Westlakes Drive, Suite 200
B.5.3.2	Town/ city	Berwyn, Pennsylvania
B.5.3.3	Post code	19312
B.5.3.4	Country	United States
B.5.4	Telephone number	0014843298432
B.5.5	Fax number	0018552756340
B.5.6	E-mail	craig.pfister@complexarx.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	CXA-10
D.3.2	Product code	CXA-10
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	10-nitro-9(E)-octadec-9-enoic acid
D.3.9.1	CAS number	88127-53-1
D.3.9.2	Current sponsor code	CXA-10
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	150 to mg
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Pulmonary Arterial Hypertension (PAH).

E.1.1.1

Medical condition in easily understood language

Patients with PAH have high pressure in the blood vessels between their heart and lungs. These have become narrow, so the heart works harder, leading to a weakened heart.

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10064911
E.1.2	Term	Pulmonary arterial hypertension
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10064911
E.1.2	Term	Pulmonary arterial hypertension
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of this study is see if CXA-10, a new study drug, when taken long term by patients with pulmonary arterial hypertension (PAH), is safe, when patients are also taking regular doses of standard PAH therapy.

The safety of CXA-10 on stable background therapy, and how well patients tolerate taking it, will be assessed by adverse event reporting (recording any unwanted symptom in a patient), including if patients experience a serious adverse or withdraw from the study due to an adverse event, and by performing and evaluating safety assessments throughout the study; vital signs (blood pressure, heart rate, breathing rate, and body temperature at baseline), Electrocardiograms (ECGs - that measure the electrical activity of the heart to show if it is working normally), laboratory safety tests on blood and urine samples, and physical examinations. The number of patients with changes in PAH therapies will also be considered.

All patients on the study will receive the same

E.2.2

Secondary objectives of the trial

The secondary objectives of this study look at safety and how well CXA-10 works.

Safety will be asssessed by how many subjects have changes in PAH-specific medications, including any dose changes over the course of the study.

To assess how well CXA-10 works, when taken long term by patients with pulmonary arterial hypertension (PAH), when patients are also taking regular doses of standard PAH therapy, the study will look at clinical measures used to assess PAH patients and if they improve.

How well CXA-10 works will be assessed by changes in: measurements of the structure and function of the right ventricle (the chamber of the heart that pumps blood to the lungs) using MRI, how far a patient can walk in 6 minutes, PAH disease biomarker level (the biomarker naturally occurs in the blood and the amount of it shows changes in PAH), WHO functional classification (a study doctor will assess how PAH is effecting a patient's physical activity), patient questionnaires, and any clinical wors

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Evidence of a personally signed and dated informed consent document indicating subject has been informed of all pertinent aspects of the study prior to initiation of any study-required procedures.
2. Is willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
3. Has completed the CXA-10-301 study and demonstrated compliance with study medication administration and all study requirements.
4. If receiving simvastatin-containing products: simvastatin (Zocor), Vytorin, or any other combination therapy containing simvastatin, simvastatin dose does not exceed 20 mg/day.
5. Currently receiving no more than three of the following previously approved PAH therapies: phosphodiesterase type 5 (PDE-5) inhibitors, endothelin receptor antagonists (ERA), soluble guanylate cyclase (sGC) stimulator, prostanoids, prostacyclin receptor agonists.
6. Women of childbearing potential and males with partners of childbearing potential must agree to use a reliable method of contraception while taking study medication. Acceptable methods of birth control are defined in the protocol.

E.4

Principal exclusion criteria

1. Severe hypotension: systolic blood pressure <90 mmHg (sitting) at Baseline (Visit 1).
2. Hypertensive: >160 mmHg systolic or >110 mmHg diastolic (sitting) at Baseline (V1).
3. QTcF on supine ECGs at Baseline (V1) of >500 msec.
4. Acute myocardial infarction or acute coronary syndrome (ST-Elevation Myocardial Infarction [STEMI], Non STEMI [NSTEMI] and or unstable angina) within the last 90 days prior to Baseline (V1).
5. Recent cerebrovascular accident/transient ischemic attack (CVA/TIA) within the last 90 days prior to Baseline (V1).
6. Recent hospitalization for left heart failure within the last 90 days prior to Baseline (V1).
7. Clinically significant aortic or mitral valve disease defined as greater than mild regurgitation or mild stenosis; pericardial constriction; restrictive or constrictive cardiomyopathy; left ventricular dysfunction (LVEF < 50%); left ventricular outflow obstruction; symptomatic coronary artery disease; autonomic hypotension; or fluid depletion, in the opinion of the investigator.
8. Chronic atrial fibrillation and life-threatening cardiac arrhythmias.
9. Personal or family history of congenital prolonged QTc syndrome or sudden unexpected death due to a cardiac reason.
10. Clinically significant anemia in the opinion of the investigator that precludes enrollment into this study, or Hb <9 gm/dl.
11. Severe hepatic impairment (Child-Pugh class C with or without cirrhosis) at Baseline (V1) or active chronic hepatitis.
12. Received intravenous inotropes within 2 weeks prior to Baseline (V1) (e.g. dopamine, dobutamine).
13. History of angina pectoris or other condition that was treated with long or short acting nitrates <12 weeks of Baseline (V1).
14. History of herbal or natural medication use (including fish oil) within 2 weeks or 5 half-lives, whichever is longer, prior to Baseline (V1).
15. Received prednisone at doses >15 mg/ day or changes in immunosuppressive medications <12 weeks prior to Baseline (V1).
16. Currently taking a drug that may affect the assay measurement of serum creatinine (e.g. cimetidine, Bactrim, Pyridium).
17. Newly prescribed drug or increased dose of an existing drug that is known to prolong the QTc interval and has been associated with Torsades de Pointes (TdP) identified in the CredibleMeds.org website list as known risk (KR) of TdP.
Note: Stable doses of drugs classified as conditional risk (CR) of TdP or possible risk (PR) of TdP are permitted (i.e., subject has received the same dose and regimen for at least 30 days prior to Baseline (V1) with no anticipated changes to the dose or regimen during the course of the study).
18. Currently taking dimethyl fumarate (Tecfidera™).
19. Any of the following laboratories abnormal and unresolved in CXA-10-301:
a. Absolute lymphocyte counts < 0.5 x 10^9 cells/L.
b. Aspartate aminotransferase and/or alanine aminotransferase > 3.0X upper limit of normal (ULN), alkaline phosphatase > 2X ULN of liver origin, and total bilirubin >2X ULN. If all liver function tests (LFTs) are within normal limits and total bilirubin is elevated, examination of direct and indirect bilirubin may be conducted to evaluate for Rotor’s/Gilbert’s Syndrome. Subjects with Rotor’s/Gilbert’s Syndrome may be enrolled.
c. eGFR < 30 mL/min/1.73 m2 (estimated by Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] Creatinine/Cystatin C 2012 algorithm) at Baseline (Visit 1).
20. Females who are pregnant or breastfeeding, or who are trying to conceive.
21. Recent (within 1 year) history of abusing alcohol or illicit drugs.
22. History of any primary malignancy, including a history of melanoma or suspicious undiagnosed skin lesions, or other malignancies (such as thyroid or testicular) that have been curatively treated and with no evidence of disease for at least 3 years or prostate cancer who is not currently or expected, during the study, to undergo radiation therapy, chemotherapy, and/or surgical intervention, or to initiate hormonal treatment.
Exception: subjects with history of basal cell or squamous cell carcinomas of the skin or cervical carcinoma in situ are eligible for enrollment.
23. Cardiovascular, liver, renal, hematologic, gastrointestinal, immunologic, endocrine, metabolic, central nervous system or psychiatric disease that, in the opinion of the investigator, may adversely affect the safety of the subject and/or efficacy of the investigational product or severely limit the lifespan of the subject other than the condition being studied.
24. Clinically significant hyperthyroidism or hypothyroidism not adequately treated.
25. Any other condition and/or situation that causes the Investigator to deem a subject unsuitable for the study
26. Known hypersensitivity to CXA-10, the metabolites, or formulation excipients.
27. Treatment with any investigational drug (other than CXA-10) or device within 30 days or 5 half-lives (whichever is longer) of baseline, or plan to do so during the study.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoints will look at safety. These are:
• Incidence of Adverse Events (AEs), Serious Adverse Events, and withdrawal due to AEs;
• Changes in vital signs, 12-lead ECG, clinical laboratory tests, and physical
examination findings over the course of the study.

E.5.1.1

Timepoint(s) of evaluation of this end point

Adverse Events, Serious Adverse Events, and withdrawal due to AEs will be collected throughout the study.

Vital signs, 12-lead ECG, clinical laboratory tests, and physical examinations will be assessed at each clinic visit during the study.

E.5.2

Secondary end point(s)

Secondary endpoints include measures of safety, efficacy, and exploratory endpoints.

Safety will be asssessed by how many subjects have changes in PAH-specific medications, including any dose changes over the course of the study.

Efficacy endpoints:
• Change from baseline in the following structural and functional parameters as measured by CMRI: Right Ventricular Ejection Fraction (RVEF), Right and Left Ventricular End Diastolic and End Systolic Volume Index (RVEDVI, RVESVI, LVEDVI and LVESVI), Right and Left Stroke Volume Index (RVSVI & LVSVI), Right and Left Ventricular Mass Index (RVMI and LVMI), Left Ejection fraction (LVEF) and Ventricular-vascular coupling estimate (RV SVI/RV ESVI) at 6 months;
• Change from baseline in 6-minute walk distance (6MWD) over the course of the study;
• Change from baseline in serum N-Terminal Pro-B-Type Natriuretic Peptide (NT proBNP) over the course of the study;
• Change from baseline in WHO Classification of Functional Status of Patients with PH over the course of the study;
• Change from baseline in Patient Reported Outcome (PRO) instrument Pulmonary Arterial Hypertension – Symptoms and Impact (PAH-SYMPACT®) Questionnaire over the course of the study;
• Change from baseline in Borg Dyspnea Index (BDI) immediately following exercise over the course of the study; and
• Clinical worsening.

Exploratory endpoints are pharmacodynamic measures:
• Additional cardiac parameters as measured by CMRI as appropriate; and
• Lipids (triglycerides, total cholesterol, low-density lipoprotein [LDL], high-density lipoprotein [HDL]), Fasting blood glucose (FBG), insulin, FBG/insulin ratios, hemoglobin A1c (where appropriate), serum leptin and serum uric acid.

E.5.2.1

Timepoint(s) of evaluation of this end point

How many subjects have changes in PAH-specific medications, including any dose changes, will be assessed throughout the study.

The Cardiac MRI is performed at 6 months.
The 6-minute walk test, WHO Classification of Functional Status, PAH-SYMPACT® Questionnaire, BDI Questionnaire and Clinical worsening are performed each clinic visit.
The test for NT proBNP is performed on each clinic visit that the patients are receiving study medication.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LSLV

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1