Clinical Trials Register

Summary
EudraCT Number:	2016-002128-10
Sponsor's Protocol Code Number:	BP39144
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2016-09-05
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

Netherlands - Competent Authority

A.2

EudraCT number

2016-002128-10

A.3

Full title of the trial

An adaptive Phase I/II study to assess safety, efficacy, pharmacokinetics and pharmacodynamics of RO7112689 in healthy volunteers and patients with paroxysmal nocturnal hemoglobinuria (PNH)

A.3.1

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

A Study to Assess Safety, Effectiveness, Pharmacokinetics, and Pharmacodynamics of RO7112689 in Healthy Volunteers and Patients With Paroxysmal Nocturnal Hemoglobinuria

A.4.1

Sponsor's protocol code number

BP39144

A.5.4

Other Identifiers

Name:

CRO code

Number:

RPU259EC-162591

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	F. Hoffmann-La Roche Ltd
B.1.3.4	Country	Switzerland
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	F. Hoffmann-La Roche Ltd
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	F.Hoffmann-La Roche Ltd
B.5.2	Functional name of contact point	Trial Information Support Line-TISL
B.5.3	Address:
B.5.3.1	Street Address	Grenzacherstrasse 124
B.5.3.2	Town/ city	Basel
B.5.3.3	Post code	4070
B.5.3.4	Country	Switzerland
B.5.6	E-mail	global.rochegenentechtrials@roche.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	RO7112689/F01
D.3.4	Pharmaceutical form	Solution for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not available
D.3.9.1	CAS number	1917321-26-6
D.3.9.2	Current sponsor code	RO7112689
D.3.9.3	Other descriptive name	C5 inh MAb, SKY59, RO/CH7092230
D.3.9.4	EV Substance Code	SUB183839
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	170
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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
D.8.3	Pharmaceutical form of the placebo	Solution for injection/infusion
D.8.4	Route of administration of the placebo	Intravenous use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection/infusion
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Paroxysmal nocturnal hemoglobinuria (PNH)

E.1.1.1

Medical condition in easily understood language

Paroxysmal nocturnal hemoglobinuria is a rare, acquired, life-threatening disease of the blood that leads to the premature death and impaired production of red blood cells

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.0
E.1.2	Level	LLT
E.1.2	Classification code	10055629
E.1.2	Term	Paroxysmal nocturnal hemoglobinuria
E.1.2	System Organ Class	100000004857

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

Part 1
•Evaluate the safety and tolerability of single doses of RO7112689 in healthy volunteers (HVs)
Part 2 and 3
•Evaluate the safety and tolerability of RO7112689 for a total duration of 5 months in treatment naïve patients with PNH and PNH patients switching treatment to RO7112689
•Evaluate the pharmacodynamic (PD) effect of multiple doses of RO7112689 on complement activity in patients with PNH

E.2.2

Secondary objectives of the trial

Part 1
•Characterize the PD effects of a single-dose of RO7112689 on complement activity (CA) & other related biomarkers
•Describe the single-dose pharmacokinetic (PK) profile of RO7112689
•Assess the bioavailability of subcutaneous (SC) administration of RO7112689
•Assess ethnic sensitivities across Japanese & non-Japanese HVs
Part 2 & 3
•Describe the multiple-dose PK properties of RO7112689 in treatment naïve patients (Pts) with PNH and PNH Pts switching treatment to RO7112689
•Characterize other PD effects of RO7112689
•Characterize the exposure-response relationship of RO7112689 following different SC dosing regimens
•Assess the efficacy, Pt-related outcomes & treatment satisfaction of RO7112689 in treatment naïve Pts with PNH, and/or PNH Pts switching treatment to RO7112689
Parts 1, 2 & 3
•Explore the PK/PD relationship of single-ascending & multiple doses of RO7112689 on CA & other related biomarkers
•Evaluate the immunogenicity of RO7112689 in HVs and in Pts with PNH

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Parts 1, 2, and 3:
- Subjects who have been vaccinated against hepatitis B
Part 1 (HVs only)
- Healthy male volunteers between the age of 21 and 55 years
- Willing to comply with a non-smoking policy during the in-clinic portion of the study
Parts 2 and 3 (PNH patients only)
- Male or female patients between the age of 18 and 75 years
- Neisseria meningitidis vaccination in accordance with most current local guidelines or Standard of Care (SOC) for patients at increased risk for meningococcal disease (Part 2)
- Patient has been vaccinated with Neisseria meningitidis vaccine(s) in accordance with most current local guidelines or SOC for patients at increased risk for meningococcal disease or is being revaccinated if applicable (Part 3)
- Stable dose for >= 28 days prior to screening of other therapies (immunosuppressant therapy, corticosteroids, iron supplements)
- Negative pregnancy test for women of childbearing potential
Part 2 only (currently untreated PNH patients who are candidates for treatment with complement inhibitors only):
- PNH patients who have not been treated with any complement inhibitor or if previously treated stopped treatment due to lack of efficacy based on a single missense C5 heterozygous mutation
- Patients had >=2 RBC transfusions in the past 12 months
Part 3 only (PNH patients currently treated with eculizumab only):
- Patients are adequately controlled (<= 2 RBC transfusions in the past 6 months)
- Patients receive regular infusions of eculizumab

E.4

Principal exclusion criteria

Parts 1, 2, and 3:
- Known or suspected hereditary complement deficiency
- History of meningococcal meningitis
- Any major episode of infection requiring hospitalization or treatment with intravenous (IV) antibiotics within 28 days prior to screening or oral antibiotics within 2 weeks prior to screening and up to first study drug administration
- History of or currently active primary or secondary immunodeficiency, including known history of HIV infection
- Evidence of malignant disease, or malignancies diagnosed within the previous 5 years

Part 1 (HVs only):
- Any clinically relevant history or the presence of moderate to severe respiratory, renal, hepatic, gastrointestinal, haematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, or connective tissue disease
- Any major illness within one month before the screening examination or any febrile illness within 2 weeks prior to screening and up to first study drug administration
- History or presence of clinically significant electrocardiogram (ECG) abnormalities or cardiovascular disease
- Congenital or acquired complement deficiency
- Carriers of Neisseria meningitides based on cultures from naso-pharyngeal swabs

Parts 2 and 3 (PNH patients only):
- Evidence of moderate to severe concurrent renal, liver, cardiac, pulmonary or gastrointestinal disease not related to PNH as determined by the Investigator
- History of bone marrow transplantation
- Treatment with azathioprine or erythrocyte-stimulating agents within 14 days prior to first study drug administration

E.5 End points

E.5.1

Primary end point(s)

Safety (Parts 1, 2, and 3):
1. Incidence of dose-limiting events
2. Incidence and severity of adverse events (AEs), serious adverse events and AEs leading to withdrawal
PD (Parts 1, 2, and 3):
3. Ex vivo liposome lysis in serum and ex-vivo lysis of antibody-coated erythrocytes
4. Total and target engaged C5 concentration
5. Serum LDH

E.5.1.1

Timepoint(s) of evaluation of this end point

Safety and PD (Parts 1, 2, and 3):
1-5. Approximately 6 months for Part 1; approximately 8 months for Parts 2 and 3

E.5.2

Secondary end point(s)

Efficacy (Parts 2 and 3):
1. Change in LDH
2. Change in free-haemoglobin
3. Proportion of patients with stabilized haemoglobin levels
4. Change in fatigue as measured by the functional assessment of chronic illness therapy fatigue
5. Change in health-related quality of life as measured by the European Organization for Research and Treatment of Cancer quality of life questionnaire-core 30
6. Number of packed RBC units transfused per patient
PK (Parts 1, 2, and 3):
7. Pharmacokinetic profile of RO7112689; Cmax, Tmax, AUC, T1/2, bioavailability following SC administration

E.5.2.1

Timepoint(s) of evaluation of this end point

Efficacy and PK (Parts 1, 2, and 3):
1-7. Approximately 6 months for Part 1; approximately 8 months for Parts 2 and 3

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)

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

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

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

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

Yes

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

Brazil

Czech Republic

France

Germany

Italy

Japan

Netherlands

United Kingdom

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

LPLV

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.1.1.1

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)

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)

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

Yes

F.3.2

Patients

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception