Clinical Trials Register

Summary
EudraCT Number:	2014-001175-31
Sponsor's Protocol Code Number:	ALM201/0001
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:	2014-08-22
Trial results	View 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

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2014-001175-31

A.3

Full title of the trial

A phase I open-label multicentre dose-escalation study of subcutaneous ALM201 in patients with advanced ovarian cancer and other solid tumours.

A.3.1

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

A study of escalating doses of ALM201 injected below the skin in patients with late stage ovarian cancer and other solid tumours.

A.4.1

Sponsor's protocol code number

ALM201/0001

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	Almac Discovery
B.1.3.4	Country	United Kingdom
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	Almac Discovery
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Ockham Europe Ltd
B.5.2	Functional name of contact point	ALM201/0001 Project Manager
B.5.3	Address:
B.5.3.1	Street Address	Logan Building, Roslin Biocentre
B.5.3.2	Town/ city	Roslin, Midlothian
B.5.3.3	Post code	EH25 9TT
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+441312006320
B.5.5	Fax number	+441312006322
B.5.6	E-mail	contact@ockham.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.3.2	Product code	ALM201
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ALM201
D.3.9.2	Current sponsor code	ALM201
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Advanced ovarian cancer and other solid tumours

E.1.1.1

Medical condition in easily understood language

Late stage cancer of the ovary and other solid tumours

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.0
E.1.2	Level	LLT
E.1.2	Classification code	10049280
E.1.2	Term	Solid tumour
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.0
E.1.2	Level	PT
E.1.2	Classification code	10033128
E.1.2	Term	Ovarian cancer
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective is to characterise the safety and tolerability of ALM201 (Part 1 and Part 2) and to identify a recommended phase 2 dose (RP2D) and schedule of ALM201 (Part 2 only)

E.2.2

Secondary objectives of the trial

The secondary objectives are:
•To establish the pharmacokinetic profile of ALM201
•To assess anti-tumour activity
•To assess anti-tumour activity in a biomarker-enriched group of patients with advanced ovarian cancer (Part 2 only)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

(i) Part 1 Specific Inclusion Criterion:
1.Patients with histologically and/or cytologically confirmed advanced solid tumour for whom no standard effective therapy is available or felt likely to be of limited efficacy and in whom a rationale for use of an anti-angiogenic treatment approach exists. Note: Previous use of anti-angiogenic therapy is allowed if tolerated.

(ii) Part 2 Specific Inclusion Criterion:
2.Patients with advanced ovarian cancer, who are intolerant of or whose tumour is resistant to platinums and who have failed to respond to, or have relapsed following, standard therapy and whose tumour has a proangiogenic profile as assessed by the angiogenesis gene signature test. Note: Previous use of anti-angiogenic therapy is allowed if tolerated.

(iii) General Inclusion Criteria for all Patients
3.Adult patients defined by age ≥16 years at time of consent.
4.Evaluable disease, either measurable on imaging, or with informative tumour marker(s), as assessed by RECIST 1.1 or other relevant response assessment criteria for tumour type.
5.Recovery from previous treatment to baseline or CTCAE ≤ Grade 1, as determined by CTCAE v4.03 criteria of reversible toxicities related to prior treatment, with the exception of alopecia, lymphopenia, other non-clinically significant adverse events; recovery from previous radiotherapy other than residual cutaneous effects or stable < Grade 2 gastrointestinal toxicity; complete recovery from surgery other than stable < Grade 2 toxicity.
6.Eastern Collaborative Oncology Group (ECOG) Performance Status (PS) of 0 or 1.
7.Laboratory values at Screening:
•Absolute neutrophil count ≥1.5 x 10e9/L without colony stimulating factor support;
•Platelets ≥100 x 10e9/L;
•Haemoglobin ≥9 g/dL (not transfusion dependent);
•Total bilirubin <1.5 times the upper limit of normal (ULN) (unless due to Gilbert’s syndrome);
•AST (SGOT) ≤2.5 times the ULN; ALT (SGPT) ≤2.5 times the ULN; ≤5 x ULN for patients with advanced solid tumours with liver metastases; patients with confirmed bony metastases will be permitted on study with isolated elevations in ALP < 5 times the ULN;
•Serum creatinine ≤1.5 x ULN or estimated glomerular filtration rate (GFR) of >50 mL/min based on the Cockcroft-Gault formula;
•Normal coagulation (elevated INR, prothrombin time or APTT ≤ 1.3 x ULN range acceptable);
•Urine protein ≤2+ (as measured by dipstick).
8.Negative urine or blood human chorionic gonadotropin (hCG) test during Screening and within 7 days of Cycle 1, Day 1 in women of childbearing potential (defined as women ≤ 50 years of age or history of amenorrhea for ≤ 12 months prior to study entry). Sexually active male and female patients of childbearing potential must agree to use an effective method of birth control e.g. barrier methods with spermicides, oral or parenteral contraceptives and/or intrauterine devices, during the entire duration of the study and for 6 months after final administration of ALM201. Note that sterility in female patients must be confirmed in the patients’ medical records and can be defined as any of the following: surgical hysterectomy with bilateral oophorectomy, natural menopause with menses >1 year ago; radiation induced oophorectomy with last menses >1 year ago; chemotherapy induced menopause with 1 year interval since last menses.
9.Ability to give written, informed consent prior to any study-specific Screening procedures, with the understanding that the consent may be withdrawn by the patient at any time without prejudice.
10.Patient is capable of understanding the protocol requirements, is willing and able to comply with the study protocol procedures, and has signed the informed consent document.

E.4

Principal exclusion criteria

1.History of inability to tolerate anti-angiogenic therapies e.g. increased blood pressure (BP), proteinuria, prior thromboembolic events.
2.Previous history of bowel obstruction, clinical evidence of gastro-intestinal obstruction, large burden of peritoneal disease or evidence of bowel involvement on computed tomography.
3.Patents has received:
a) any chemotherapy regimens (including investigational agents) with delayed toxicity within 4 weeks (6 weeks for prior nitrosourea or mitomycin C) of Cycle 1, Day 1, or received chemotherapy regimens given continuously or on a weekly basis which have limited potential for delayed toxicity within 2 weeks of Cycle 1, Day 1.
b) radiotherapy, immunotherapy or biological agents (includes investigational agents) within 4 weeks of Cycle 1, Day 1. Localised palliative radiotherapy is permitted for symptom control.
4.Documented, symptomatic or uncontrolled intracranial metastases or primary intracerebral tumours.
5.Cancer with leptomeningeal involvement.
6.On therapeutic anti-coagulation (aspirin dosing ≤100 mg per oral (PO) daily allowed).
7.Previous malignancy, except for non-basal-cell carcinoma of skin or carcinoma-in-situ of the uterine cervix, unless the tumour was treated with curative intent more than 2 years prior to study entry.
8.History of clinically significant cardiac condition, including uncontrolled hypertension (BP >140/90 mmHg, despite medical therapy); left ventricular systolic dysfunction (ejection fraction (<55 %) on echocardiography) with or without heart failure symptoms; history of an ischaemic cardiac event within 3 months of study entry (myocardial infarction, acute coronary syndrome); QT interval prolongation (QTcF, Fridericia’s Correction of >450 ms on screening 12-lead ECG); clinically significant cardiac arrhythmia within 3 months of study entry. Note: ventricular tachycardia, ventricular fibrillation, supraventricular tachycardia, atrial fibrillation without adequate heart rate control, atrial fibrillation with adequate heart rate control with or without medication or other treatment, are not an exclusion.
9.Known human immunodeficiency virus positivity.
10.Active hepatitis B or C or other active liver disease (other than malignancy).
11.Any active, clinically significant, viral, bacterial, or systemic fungal infection within 4 weeks prior to Cycle 1, Day 1.
12.Any evidence of severe or uncontrolled systemic conditions or any other issues which make it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol.

E.5 End points

E.5.1

Primary end point(s)

•Ongoing evaluation of AEs during treatment and follow up; evaluation of DLT during Cycle 1 (Part 1 only)
•Safety, PK, PD and tumour response assessments for identification of RP2D

E.5.1.1

Timepoint(s) of evaluation of this end point

Adverse events will be noted at every clinical visit & recorded at least every week. Evaluation of DLT ongoing throughout Part 1.
Safety assessed throughout study.
A PK profile for ALM201 will be taken on Days 1, 3 & 18 of Cycle 1 & on Day 18 of Cycles 2, 4, 6 & 8. Pre-dose samples will also be taken on Cycles 2-8 on Day 1.
Biopsies for biomarker/PD evaluation will be taken at Screening & up to 2 post-treatment. Up to 12 post-treatment biomarker/PD samples in blood and 2 post-treatment biomarker/PD samples in ascites will be taken.
Tumour assessment by imaging, or informative markers where relevant, will be assessed at Screening & after every 2 cycles of treatment during Cycles 1–8 & then after every 4 cycles, & may be performed at other times as clinically indicated.

E.5.2

Secondary end point(s)

•Assessment of pharmacokinetic variables (including Cmax, Cmin, AUC)
•Tumour response assessment by RECIST 1.1 and/or other relevant response assessments for tumour types enrolled

E.5.2.1

Timepoint(s) of evaluation of this end point

Patients will have a 12-hour urine collection on Cycle 1, Day 1 for urine PK analysis.
Patients will have PK blood sampling conducted at Cycle 1, Day 1; Cycle 1, Day 3 & 18; Cycles 2, 4, 6 & 8, Day 18.
A single pre-dose sample will also be taken on Cycles 2-8, on Day 1.
Tumour assessment will follow RECIST 1.1 after every 2 cycles.

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

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

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)

Yes

E.7.1.1

First administration to humans

Yes

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)

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

Yes

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.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

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

LVLS. Patients will continue to be followed up every 8 weeks for up to approximately a 2 year period, to check their disease (survival) status.

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

Yes

F.1.1

Number of subjects for this age range:

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Most patients will receive normal standard of care. Patients may be permitted to receive further consecutive cycles of ALM201 where their cancer has not progressed on study and their investigator recommends this course of action, subject to availability of ALM201.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2014-10-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-08-29

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2017-05-23

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