Medical Affairs Concept Sheet (MACS) For Investigator Initiated Trials: Part 1

(applies to Oncology and Gen Meds Interventional Third Party Sponsored, Investigator Initiated Trials)

MEDICAL AFFAIRS CONCEPT SHEET (MACS) IS IIT

Instructions: ALL RED FONT CAN BE DELETED ONCE THE FORM IS COMPLETED. All sections must be
completed before this Concept Sheet will be reviewed.
Investigator DR. Arief S. Kartasasmita, dr., SpM(K)
Sponsor/Group/
Institution
(if applicable)
Mailing Address

Phone/Fax
Email Address
Novartis Country Yuriawati Hendrawan
Medical
Responsible Name
Novartis Country yuriawati.hendrawan@novartis.com
Medical
Responsible Email
Country Indonesia
Product Lucentis
Primary Product
Secondary Product YES NO
Is Secondary Product a Novartis YES NO
Drug?
If YES:
Is Secondary Product a Comparator? YES NO
If YES:
Tertiary Product YES NO
Is Tertiary Product a Novartis Drug? YES NO
If YES:
Is Tertiary Product a Comparator? YES NO
If YES:
Indication Diabetic macular edema (DME), Wet age-related macular degenertion (AMD),
choridal neovascularization (CNV) secondary to pathologic myopia (PM)
Title of Trial A Prospective, Mono-Center, Experimental Study Assessing Two Consecutive

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Medical Affairs Concept Sheet (MACS) For Investigator Initiated Trials: Part 1
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Injections of Ranibizumab Prior to Laser Photocoagulation and Laser

Photocoagulation as Mono-Therapy in Patients with Diabetic Macular Edema
Trial Phase Phase IV
(if applicable)
Request for YES √ NO
Financial Support?
If YES, budget (USD) requested for
the trial:
Request for Drug YES NO
Supply
If YES, specify drug supply requested
(active drugs, comparators,
placebo):
Rationale for Trial [Summarize the rationale (e.g. medical need, advantage of suggested
innovative approach over current best medical practice]
Summarize the Objective Endpoint
Primary, Secondary
Primary To evaluate the efficacy of BCVA
and Exploratory
ranibizumab administered as
Objectives with the
a two consecutive injections
Associated
prior to laser
Endpoints and
photocoagulation compare
Evaluation Criteria
with laser photocoagulation
mono-therapy in patients
with visual impairment due
to diabetic macular edema.
The variable for this objective
will be the mean change best
corrected visual acuity
(BCVA) from baseline over six
month study period
Secondary/ To evaluate macular Macular thickness based on
thickness based on optical
Exploratory coherence tomography
OCT
(OCT) examination of
ranibizumab administered as
two consecutive injections
prior to laser
photocoagulation compare
with laser photocoagulation
monotherapy in patients with
visual impairment due to
diabetic macular edema at
Month 1 after laser
photocoagulation
administered

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Medical Affairs Concept Sheet (MACS) For Investigator Initiated Trials: Part 1
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Trial Design Enter a concise overview of the trial design in this space, including:
- A prospective, randomized, mono-center, experimental study
- Purpose (e.g. safety, efficacy, long-term tolerability)
- Number of arms: 2 arms
- Translational research that will be performed.
- For dose escalation trials include definition of MTD and DLT as well as
cohort levels (see below chart)
- Blinding: Open ( ) Single Blind (√ ) or Double Blind ( )
- Structure: None ( ) , Single Group ( ), Parallel Group ( ), Cross over ( )
Intrasubject ( )
- Randomized: Randomized (√ ) or Non-randomized ( )

Cohort levels for Dose Escalation Trials Only:

No of pts Cohort Level Drug A (dose & Drug B (dose &
Frequency) Frequency) (if
applicable)

Population Patients with mild to moderate non proliferative diabetic retinopathy and
diabetic macular edema
Key Inclusion 1) Males or females patients with age 20 years and older
Criteria 2) Patients with type 1 or type 2 diabetes mellitus according to
WHO criteria
3) HbA1C ≤ 12 %
4) Patients with intraocular pressure < 21 mmHg.
5) Laser photocoagulation in the study eye can be withheld for
at least 3 months after randomization.
6) Patients with visual impairment due to focal or diffuse DME
in at least one eye that was eligible for laser treatment in the
opinion of the investigator. If both eyes were eligible, the eye
with the worse visual acuity will be selected for study
treatment. The study eye had to fulfill the following criteria :
 BCVA score between 80 and 40 letters, inclusively,
using ETDRS-like visual acuity testing charts at a
testing distance of 4 meters (approximate Snellen
equivalent of 20/32 to 20/160)
 Decrease in vision due to DME and not due to other
causes, in the opinion of the investigator

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Key Exclusion 1) Patients with uncontrolled systemic disease, e.g.

Criteria uncontrolled diabetes mellitus, uncontrolled
hypertension, history of thromboembolic events
including myocardial infarction, cerebral insult and renal
disease.
2) Ocular diseases other than DME.
3) Laser photocoagulation in the study eye within 3 months
prior to randomization.
4) Treatment with any anti-VEGF agents in study eye within
3 months prior to randomization.
5) Have any history of any intraocular surgery in the study
eye within the past 6 months preceding screening.

6) Conditions that require chronic concomitant therapy with

systemic and/or topical ocular corticosteroids.

7) Investigational agents for DME (including intravitreal,

subconjunctival or subtenons corticosteroids) for the
last 3 months.

8) Pregnancy.

Gender Males √ Females √

Minimum Age 18 years old
Maximum Age No maximum age
Planned Trial Trial Start
Milestone Dates (First Patient First Visit)
(Month and Year
Recruitment End
MUST be entered
for each item) (Last Patient First Visit)
Trial End
(Last Patient Last Visit)
Completion of Trial
Report
(Final Trial Report to be
sent to Novartis no later
than 12 months after
Last Patient Last Visit. [6

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months for pediatric

trials])
Primary Publication
Date
(Publication to be sent
to Novartis no later than
24 months after Last
Patient Last Visit)
Number of Patients Total Planned Number 30
and Centers of Patients
Planned Number of 1
Centers
Planned Number of Indonesia
Countries
(List the Countries)
Sample Size [Provide sample size justification by clearly stating the statistical assumptions,
Justification and level of significance and power. If no formal sample size calculation was done,
Statistical Analysis provide an explanation why such a calculation was not done.]
[Provide a brief description of the statistical hypothesis and methods for data
analysis, focusing on the analysis of the primary objective if available.]
Treatment How many treatment 2
Information arms apply to this
(includes trial?
Co-Therapy) Complete the table below for each arm.
Generic
Compound Acceptable?
Treatment # of Pts Type of Trial (specify Min Dose Max Dose Admin
Frequency (applies only
Arm Planned Drug brand or and Unit and Unit Route
generic) for
comparable)
Ranibizuma 15 Investigational Lucentis 0,5 mg Twice in 2 Intravitreo Yes/No/NA
b consective us
months

Comparator

Co-therapy

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Field Definitions:
Treatment Arm Can be a number or letter as per protocol
Number of Patients Number of planned patients per treatment arm
Planned
Type of Trial Drug Enter either Investigational, Co-Therapy or Comparator for
each compound within each treatment arm
Compound Enter all Novartis & External Drugs that apply (For
comparator compounds please specify if branded or generic
will be used)
Min/Max Dose 30 mg, 50 mg etc.
Frequency Daily, weekly,……
Administrative Route IV, PO…..
Generic Acceptable Only applies to ‘Comparators’ (Select Yes or No)

IRB Registration Has the institutional IRB been registered into the internet-based
Requirement registration system maintained by the US Department of Health and
THIS ONLY APPLIES TO Human Services?
TRIALS CONDUCTED IN YES NO
THE UNITED STATES
IRBs that are not registered must submit an initial registration
electronically through http://ohrp.cit.nih.gov/efile or in writing to the
N/A Good Clinical Practice Program (HF-34), Office of Science and Health
Coordination, Food and Drug Administration, 5600 Fishers Lane, Rockville,
MD 20857.
Pharmacovigilance The minimum requirements for Adverse Event (AE) collection are
Requirements presented in the table below. Please identify the type of trial you are
proposing and note the Novartis requirements for what adverse event
data must be collected during the course of the trial. You may only check
one (by double-clicking on the box and choose the default value as
“checked”). If your proposal is approved, these requirements must be
reflected fully in the protocol.
INTERVENTIONAL WITH a Novartis Drug WITH NO Novartis Drug
TRIAL
Must be collected: Must be collected:
• All Serious Adverse Events (SAE) • All SAEs*
• All reports of drug exposure during • All non-serious AEs*
pregnancy
• All non-serious Adverse Events (AE) *Relationship between the
• All reports of misuse and abuse of AE/SAE and the trial conduct
the Novartis drug, other medication would be expected to be

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errors and uses outside of what is collected rather than

foreseen in the protocol relationship to trial drug.
(irrespective if a clinical event has
occurred)
Adverse Events Exempt [If there are any SAEs or AEs that are proposed to be exempted from
from Collection collection, please detail these here]

The requirements for the transfer to Novartis of adverse event data collected from the trial,
including timeframes, are defined in the IIT Agreement. For trials involving patients treated with a
Novartis drug, the Novartis safety requirements include:
 Provision of the randomization codes (for blinded trials) to Novartis
 Transfer to Novartis in an ongoing manner of reports of SAEs, drug misuse or abuse, reports
of drug exposure during pregnancy, any other information that may suggest a change in the
benefit-risk profile for the Novartis drug, and where required, copies of Investigator
Notifications for suspected unexpected serious adverse events (SUSAR) and copies of the
Development Safety Update Report
 Performing an adverse event reconciliation between the Sponsor’s trial database and an
output from the Novartis safety database periodically throughout the trial.
Once the study concept is approved and the IIT agreement is executed, please refer to the IIT
agreement for exact requirements for the type of trial you are proposing.

Key References [Please list all key references here.]

Investigator Attestation Statement

Novartis supports medically and scientifically sound independent research initiated by external
investigators and aimed at the advancement of scientific knowledge in therapeutic areas of interest
for Novartis. Novartis evaluates unsolicited proposals from independent researchers or their
institutions for support. By signing below you represent that:
 the research proposal you are submitting was independently conceived by you and not solicited
by any Novartis employee,
 you have prior clinical research experience within the previous three years of concept
submission,
 the trial will be executed only by you and your staff that have received GCP training within the
previous three years of concept submission,
 you have the capability and infrastructure to run the IIT in an ethical and compliant manner
 you will comply with Novartis safety requirements,
 you assume all of the responsibilities in your role as the Sponsor and Investigator per ICH GCP
guidelines/Ethical Guidelines for Medical and Health Research Involving Human Subjects.
Investigator’s Name and Signature (MUST BE WET SIGNATURE)

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Medical Affairs Concept Sheet (MACS) For Investigator Initiated Trials: Part 1
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Name
Signature
Date

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