A PHASE II, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED DOSE-RANGING STUDY TO EVALUATE LEBRIKIZUMAB (MILR1444A) IN ADULT PATIENTS WITH ASTHMA WHO ARE NOT TAKING INHALED CORTICOSTEROIDS (MOLLY) - MOLLY

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2009-013267-19-HU
• Date of registration: 21/09/2009
• Prospective Registration: Yes
• Primary sponsor: GENENTECH, Inc.
• Public title: A PHASE II, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED DOSE-RANGING STUDY TO EVALUATE LEBRIKIZUMAB (MILR1444A) IN ADULT PATIENTS WITH ASTHMA WHO ARE NOT TAKING INHALED CORTICOSTEROIDS (MOLLY) - MOLLY
• Scientific title: A PHASE II, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED DOSE-RANGING STUDY TO EVALUATE LEBRIKIZUMAB (MILR1444A) IN ADULT PATIENTS WITH ASTHMA WHO ARE NOT TAKING INHALED CORTICOSTEROIDS (MOLLY) - MOLLY
• Date of first enrolment: 16/10/2009
• Target sample size: 200
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-013267-19
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Hungary

Key inclusion & exclusion criteria

Inclusion criteria:
Patients must meet the following criteria to be eligible for study entry:

103 Age = 18 and = 65 years at Visit 1

105 Chest radiograph within 12 months of Visit 1 without evidence of a clinically significant abnormality other than changes consistent with asthma

107 Stable asthma defined by the following criteria (patients must meet all of the criteria):
1. Diagnosis of asthma = 12 months prior to Visit 1
2. Bronchodilator response at Visit 1 or Visit 2
3. Prebronchodilator FEV1 = 60% and =85% predicted at Visit 3
4. Stable disease: Relative change in pre-bronchodilator FEV1 (volume) from Visit 2 to Visit 3 is <15% (increase or decrease).
Relative change in mean morning pre-bronchodilator peak flow between Visit 1 and 2 must be < 20% (increase or decrease) of the mean pre-bronchodilator peak flow between Visits 2 and 3.
Daily use of albuterol metered dose inhaler (MDI) (or equivalent) must be < 10 puffs or = 2 nonscheduled administrations (or any new use) of nebulized SABA therapy
No required ICS, oral or parenteral corticosteroids

Are the trial subjects under 18? no
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) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Patients who meet any of the following criteria will be excluded from study entry:

a.Medical Conditions
201 Known malignancy or current evaluation for a potential malignancy. If treatment for a malignancy was completed at least 12 months prior to Visit 1 and no further treatment is anticipated by the patient’s oncologist during this study, then the patient may enroll.

202 Patients with a new diagnosis of basal cell carcinoma or squamous cell skin carcinoma in the 12 months prior to the run-in period are excluded.

203 Known immunodeficiency, including but not limited to HIV infection

204 Clinically significant medical disease that is uncontrolled despite treatment or is likely in the opinion of the investigator to require a change in therapy during the study

205 Patients with elevated IgE levels for reasons other than allergy (including but not limited to parasitic infections, hyperimmunoglobulin E syndrome, allergic bronchopulmonary aspergillosis, and Wiskott-Aldrich syndrome)

206 Patients with a history of or active infection with any GI nematodes (including, though not limited to, enterobiasis; trichuriasis; hookworm; strongyloidiasis; trichinellosis; ascariasis) or leishmaniasis or lymphatic filariasis; regardless of treatment status

207 Any other medical condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the patient at high risk for treatment complications

209 Lung disease other than asthma including but not limited to active infection

b. Exposures
210 Current smoker or former smoker with a lifetime smoking history of > 10 pack years.

211 History of substance abuse that may impair or risk the patient’s full participation in the study, in the judgment of the investigator
212 Participation in another interventional clinical trial (including interventional studies that does not include use of medication) within 30 days

c.Medications
213 Use of any of the excluded medications during the time periods listed in Table 1 of protocol

214 Prior allergic reaction during the use (or possible use if blinded study) of a monoclonal antibody

d. Reproductive Potential
215 Patients (men and women) of reproductive potential who are not willing to use a highly effective method of contraception (see Appendix B) for the duration of the study or women who are pregnant or lactating at the time of random allocation

216 Women with a positive serum pregnancy test



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Asthma in adult patients not taking inhaled corticosteroids
MedDRA version: 12.0 Level: LLT Classification code 10003553 Term: Asthma

Intervention(s)

Product Name: Lebrikizumab
Product Code: MILR1444A
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Lebrikizumab
CAS Number: 953400-68-5
Current Sponsor code: MILR1444A
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 125-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Main Objective: The main objectives of this study are as follows;

- To evaluate the efficacy of different doses of lebrikizumab compared with placebo as measured by relative change in pre-bronchodilator FEV1.

- To evaluate the safety and tolerability of different doses of lebrikizumab.

Primary end point(s): The primary efficacy outcome measure is the relative change in pre-bronchodilator
FEV1 (volume) from baseline to Week 12.

Secondary Objective: The secondary objectives of this study are as follows:
- To compare the efficacy among different doses of lebrikizumab as measured by relative change in pre-bronchodilator FEV1.

- To evaluate the efficacy of different doses of lebrikizumab compared with placebo in a subgroup of IL-13 signature surrogate positive patients, as measured by relative change in pre-bronchodilator FEV1.

- To evaluate the efficacy of different doses of lebrikizumab compared with placebo as measured by change in morning peak flow, peak flow variability, rescue medication use, and time to treatment failure.

- To characterize the PK of lebrikizumab.

Secondary ID(s)

ILR4660g