Clinical Trials Register

Summary
EudraCT Number:	2018-004926-26
Sponsor's Protocol Code Number:	PRV-031-001
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2020-06-30
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

2018-004926-26

A.3

Full title of the trial

A Phase 3, Randomized, Double-Blind, Multinational, Placebo-Controlled Study to Evaluate Efficacy and Safety of Teplizumab (PRV-031), a Humanized, FcR Non-Binding, anti-CD3 Monoclonal Antibody, in Children and Adolescents with Newly Diagnosed Type
1 Diabetes (T1D)

A.3.1

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

A phase 3 clinical study of teplizumab for treatment of children and adolescents with newly diagnosed type 1 diabetes

A.3.2

Name or abbreviated title of the trial where available

PROTECT

A.4.1

Sponsor's protocol code number

PRV-031-001

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/8/2010

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Provention Bio, 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	Provention Bio, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Provention Bio, Inc.
B.5.2	Functional name of contact point	Sharon Rowland
B.5.3	Address:
B.5.3.1	Street Address	P.O. Box 666
B.5.3.2	Town/ city	Oldwick, NJ
B.5.3.3	Post code	08858
B.5.3.4	Country	United States
B.5.4	Telephone number	443-987-0797
B.5.6	E-mail	srowland@proventionbio.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	Teplizumab
D.3.2	Product code	PRV-031
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Teplizumab
D.3.9.1	CAS number	876387-05-2
D.3.9.2	Current sponsor code	PRV-031
D.3.9.3	Other descriptive name	TEPLIZUMAB
D.3.9.4	EV Substance Code	SUB35383
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	1.0
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	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
D.8.3	Pharmaceutical form of the placebo	Concentrate for solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Type 1 Diabetes (T1D)

E.1.1.1

Medical condition in easily understood language

Type 1 Diabetes

E.1.1.2

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10012594
E.1.2	Term	Diabetes
E.1.2	System Organ Class	100000004861

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To determine whether two courses of teplizumab slow the loss of β cells and preserve β cell function over 18 months (78 weeks) in children and adolescents 8-17 years old who have been diagnosed with T1D in the previous 6 weeks.

E.2.2

Secondary objectives of the trial

• To evaluate participant improvements in key clinical parameters of diabetes management, including insulin use, glycemic control (including hemoglobin A1c [HbA1c] and and time in glycemic target range [TIR]),
• To determine the safety and tolerability of two courses of teplizumab, administered intravenously (IV)
• To evaluate the pharmacokinetics (PK) and immunogenicity of two courses of IV teplizumab

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Participant is male or female.
2. Participant is 8 to 17 years of age, inclusive, at the time of randomization/initiation of study drug
administration.
3. Participant has received a diagnosis of T1D according to the criteria from the American Diabetes
Association (ADA)
4. Participant is able to be randomized and initiate study drug within 6 weeks (42 days) of the formal
T1D diagnosis according to the ADA criteria.
5. Participant has a peak stimulated C-peptide of ≥0.2 pmol/mL from a 2-hour mixed meal tolerance
test (2h MMTT) at screening. (Note: This screening 2h MMTT must occur only after 6 days
following diagnosis to allow for reduction of metabolic instability.)
6. Participant has a positive result on testing for at least one of the following T1D-related
autoantibodies before randomization:
• Glutamic acid decarboxylase 65 (GAD65) autoantibodies
• Islet antigen 2 (IA-2) autoantibodies
• Zinc transporter 8 (ZnT8) autoantibodies
• Islet cell cytoplasmic autoantibodies (ICA) or
• Insulin autoantibodies (if testing obtained within the first 14 days of insulin treatment)
7. Female participants of childbearing potential must have a negative result on highly sensitive serum (β human chorionic gonadotropin [β-HCG]) at screening and at randomization.
8. Participants who have reached puberty must agree to adhere to the following contraceptive requirements. (Note: In countries with legislation for the age of sexual activity, the participant must comply with the local age limit regarding the use of contraception):
•Females with childbearing potential (defined as premenopausal females who are capable of becoming pregnant, i.e, having reached menarche or having reached Tanner stage 3 breast development even without menarche) or who gain childbearing potential during the study must practice abstinence or use 2 forms of contraception (including oral, transdermal, injectable, or implanted contraceptives, intrauterine device, female condom, diaphragm with spermicide, cervical cap, use of a condom by the sexual partner, or a sterile sexual partner) continuously from 30 days before
the first dose of study drug through the end of the study.
• Males who have reached puberty (ie, spermatogenesis) with partners of childbearing potential must use barrier contraception in addition to having their partners use another method of contraception from 1 week before each study agent dose through 120 days (a complete spermatogenesis cycle) after receiving the last dose in each treatment
course.
9. Prior to receiving study drug, participant must be up to date with and/or agree to receive routine
age-appropriate immunizations and comply with the guidelines for immunosuppressed individuals
and those with chronic disease (diabetes mellitus) according to current local, regional and/or
country-specific guidelines.
10. Participant agrees not to receive other forms of experimental treatment during the study,
particularly agents that may be immune modulatory in nature and/or stimulate pancreatic β cell
regeneration or insulin secretion
11. Participant and/or appropriate legal guardian must sign an informed consent form (ICF) and/or
assent according to local, regional and/or country-specific guidance for study participation.

E.4

Principal exclusion criteria

1. Participant has known allergies, severe reaction, intolerance, hypersensitivity, or anaphylaxis to human, humanized, or murine monoclonal antibodies, teplizumab or any of its components or its excipients.
2. An active participant in a therapeutic drug, invasive medical device, or vaccine clinical trial within 12 weeks before the first dose of drug or has received an investigational treatment with the potential for T1D disease modification.
3. Significant renal, cardiac, vascular, pulmonary, gastrointestinal, neurologic, hematologic, rheumatologic, oncologic, psychiatric disease, or immune deficiency.
4. Any autoimmune disease other than T1D (eg, rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, multiple sclerosis, systemic lupus erythematous, with the exception of clinically stable thyroid or celiac disease.
5. Active infection (including a positive SARS-CoV-2 test) and/or fever ≥38.5°C (101.3°F) within the 48 hours prior to randomization, is prone to infections, or has chronic, recurrent or opportunistic infectious disease, including but not limited to renal, respiratory or skin infections, Pneumocystis carinii, aspergillosis, latent or active granulomatous infection, histoplasmosis, or coccidioidomycosis.
6. Participant has a history of or serologic evidence at screening of current or past infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV).
7. Participant has any of the following in regards to tuberculosis (TB): history of latent or active TB, signs and/or symptoms of TB, recent close contact with a person with known or suspected active TB, history of a chest X-ray consistent with active TB or old, inactive TB, history of a positive purified protein derivative skin test result (>10 mm induration) or at screening is positive or repeatedly indeterminate with an approved interferon-gamma
release assay (IGRA; eg, QuantiFERON-TB test); recent (within 3 months) chest X-ray or one conducted at screening read by a qualified radiologist consistent with current, active TB or old, inactive TB
8. At screening, participant has a clinically active infection with EBV, including but not limited to infectious mononucleosis, or an EBV viral load ≥10,000 copies per mL or per 10^6 lymphocytes obtained at screening.
9. At screening, participant has a clinically active infection with CMV or a CMV viral load 10,000 copies per mL or per 10^6 lymphocytes.
10. Participant has a diagnosis of significant liver disease or at screening alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >2X or total bilirubin (TBili) of >1.5X of the age- and sex-specific upper limit of normal (ULN) according to the central laboratory (Note: participants with Gilbert's syndrome may be allowed to enroll upon approval by the Medical Monitor).
11. An individual has any of the following hematologic parameters:
• Lymphocyte count: <1000/µL
• Neutrophil count: <1000/µL
• Platelet count: <100,000 platelets/µL
• Hemoglobin: <10 g/dL
12. Current or prior treatment that is known to cause a significant, ongoing change in the course of T1D or immunologic status, including high-dose inhaled, extensive topical, or systemic glucocorticoids.
13. Current or prior use of drugs other than insulin to treat hyperglycemia.
14. Current or prior use of any medication known to significantly influence glucose tolerance (eg, atypical antipsychotics, diphenylhydantoin, niacin).
15. Current or planned highly restrictive dietary regimen(s) intended for T1D management, such as very low or ultra low carbohydrate diets.
16. Recent or planned vaccinations as follows:
• Live vaccines: Within the 8 weeks before randomization and initiation of study drug or planned/required administration through Week 52 of the study.
• Non-infectious vaccines: Within 8 weeks before or after each dosing course.
17. A female who is pregnant, has a positive β-HCG blood test at screening or a positive urine β-HCG
test prior to initiation of study drug, wishes to become pregnant, is planning on donating eggs (ova,
oocytes), and/or is lactating with the intent to provide her own breast milk to a baby during the
entire study.
18. A male who is planning to father a child or donate sperm from 1 week before each study agent dose
through 120 days (a complete spermatogenesis cycle) after receiving the last dose in each treatment
course.
19. An individual who has a history of alcohol, drug, or chemical abuse within 12 months prior to screening.
20. An individual who has a medical, psychological or social condition that, in the opinion of the
PI, would interfere with safe and proper completion of the trial.
21. An individual who is an employee of the Investigator or study site, with direct involvement in the
proposed study or other studies under the direction of that Investigator or study site, as well as
family members of the employees or the Investigator.

E.5 End points

E.5.1

Primary end point(s)

The area under the time-concentration curve (AUC) of C-peptide after a 4-hour (4h) mixed meal tolerance test (MMTT), a measure of endogenous insulin production and β cell function, at Week 78.

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 78

E.5.2

Secondary end point(s)

• Exogenous insulin use: defined as a daily average in units per kilogram per day (U/kg/day), at Week 78
• HbA1c levels: expressed in % and mmol/mol, at Week 78
• TIR: expressed as a daily average of the percentage of time in a 24 hour-day a participant’s BG is >70 but ≤180 mg/dL (>3.9 to ≤10.0 mmol/L) assessed using continuous glucose monitoring (CGM), at Week 78
• Clinically important hypoglycemic episodes: defined as the total number of episodes of a BG reading of <54 mg/dL (3.0 mmol/L) and/or episodes of severe cognitive impairment requiring external assistance for recovery, from randomization through Week 78

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 78

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

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

Yes

E.6.13.1

Other scope of the trial description

Immunogenecity, tolerability

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

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

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

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

Belgium

Canada

Czech Republic

Finland

France

Germany

Hungary

Poland

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

Yes

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

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:

300

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:

300

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

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.4.2

For a multinational trial

F.4.2.1

In the EEA

135

F.4.2.2

In the whole clinical trial

300

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)

There are no plans for treatment or care for subjects after the trial.

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

2019-07-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-07-26

P. End of Trial
P.	End of Trial Status	GB - no longer in EU/EEA

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