Trial Outcomes & Findings for Phase 3 Study of Intranasal Carbetocin (LV-101) in Patients With Prader-Willi Syndrome (NCT NCT03649477)

Last Updated: 2022-07-26

Results Overview

Change in hyperphagia (extreme hunger) as measured by the Hyperphagia Questionnaire for Clinical Trials (HQ-CT) Total Score versus placebo. Score range: 0-36; higher scores mean a worse outcome. Reduction in score indicates improvement.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

130 participants

Primary outcome timeframe

Baseline to Week 8

Results posted on

2022-07-26

Participant Flow

Participants were enrolled in three countries, the United States, Canada and Australia. The first participant was screened in November 2018, the first participant was enrolled in December 2018, and the last participant was enrolled in March 2020.

Subjects were randomized 1:1:1 at Baseline to receive the 9.6 mg/dose, 3.2 mg/dose, or placebo during the 8-week placebo-controlled period. A total of 130 subjects were evaluated (44 subjects in the 9.6 mg/dose arm, and 43 subjects each in the 3.2 mg/dose and placebo arms). Of these 130 subjects, 128 subjects (98.5%) completed the Week 8 visit and entered into the long-term follow-up period.

Participant milestones

Participant milestones
Measure	9.6 mg of LV-101 9.6 mg of LV-101 during the 8-week placebo-controlled period 9.6 mg intranasal carbetocin: three times per day with meals	3.2 mg of LV-101 3.2 mg of LV-101 during the 8-week placebo controlled period 3.2 mg intranasal carbetocin: three times per day with meals	Placebo Matched intranasal placebo during the 8-week placebo controlled period placebo: three times per day with meals
Overall Study STARTED	44	43	43
Overall Study COMPLETED	42	43	43
Overall Study NOT COMPLETED	2	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	9.6 mg of LV-101 9.6 mg of LV-101 during the 8-week placebo-controlled period 9.6 mg intranasal carbetocin: three times per day with meals	3.2 mg of LV-101 3.2 mg of LV-101 during the 8-week placebo controlled period 3.2 mg intranasal carbetocin: three times per day with meals	Placebo Matched intranasal placebo during the 8-week placebo controlled period placebo: three times per day with meals
Overall Study Adverse Event	2	0	0

Baseline Characteristics

Phase 3 Study of Intranasal Carbetocin (LV-101) in Patients With Prader-Willi Syndrome

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	9.6 mg of LV-101 n=44 Participants 9.6 mg of LV-101 during the 8-week placebo-controlled period 9.6 mg intranasal carbetocin: three times per day with meals	3.2 mg of LV-101 n=43 Participants 3.2 mg of LV-101 during the 8-week placebo controlled period 3.2 mg intranasal carbetocin: three times per day with meals	Placebo n=43 Participants Matched intranasal placebo during the 8-week placebo controlled period placebo: three times per day with meals	Total n=130 Participants Total of all reporting groups
Age, Categorical <=18 years	42 Participants n=5 Participants	43 Participants n=7 Participants	43 Participants n=5 Participants	128 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Female	21 Participants n=5 Participants	27 Participants n=7 Participants	24 Participants n=5 Participants	72 Participants n=4 Participants
Sex: Female, Male Male	23 Participants n=5 Participants	16 Participants n=7 Participants	19 Participants n=5 Participants	58 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	5 Participants n=7 Participants	4 Participants n=5 Participants	13 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	40 Participants n=5 Participants	38 Participants n=7 Participants	39 Participants n=5 Participants	117 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Race (NIH/OMB) White	37 Participants n=5 Participants	37 Participants n=7 Participants	37 Participants n=5 Participants	111 Participants n=4 Participants
Race (NIH/OMB) More than one race	3 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	9 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline to Week 8

Population: Primary Analysis Set: A subset of the Full Analysis Set that included all subjects with at least one post-Baseline visit (i.e., Week 2 or Week 8) completed prior to March 01, 2020 and excluded all efficacy data collected on or after March 01, 2020.

Outcome measures

Outcome measures
Measure	9.6 mg of LV-101 n=40 Participants 9.6 mg of LV-101 during the 8-week placebo-controlled period 9.6 mg intranasal carbetocin: three times per day with meals	3.2 mg of LV-101 n=39 Participants 3.2 mg of LV-101 during the 8-week placebo controlled period 3.2 mg intranasal carbetocin: three times per day with meals	Placebo n=40 Participants Matched intranasal placebo during the 8-week placebo controlled period placebo: three times per day with meals
Hyperphagia Behavior	-3.439 score on a scale Interval -5.304 to -1.575	-5.372 score on a scale Interval -7.259 to -3.486	-2.237 score on a scale Interval -4.095 to -0.378

PRIMARY outcome

Timeframe: baseline to Week 8

Change in obsessive and compulsive behaviors as measured by the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) Total Score versus placebo. Score range: 0-40; higher scores mean a worse outcome. Reduction in score indicates improvement.

Outcome measures

Outcome measures
Measure	9.6 mg of LV-101 n=40 Participants 9.6 mg of LV-101 during the 8-week placebo-controlled period 9.6 mg intranasal carbetocin: three times per day with meals	3.2 mg of LV-101 n=39 Participants 3.2 mg of LV-101 during the 8-week placebo controlled period 3.2 mg intranasal carbetocin: three times per day with meals	Placebo n=40 Participants Matched intranasal placebo during the 8-week placebo controlled period placebo: three times per day with meals
Obsessive and Compulsive Behaviors	-2.968 score on a scale Interval -4.667 to -1.268	-3.123 score on a scale Interval -4.843 to -1.403	-2.360 score on a scale Interval -4.046 to -0.674

SECONDARY outcome

Timeframe: Baseline to Week 8

Change in participant anxiety as measured by the PWS Anxiety and Distress Questionnaire (PADQ) Total Score versus placebo. Score range: 0-56; higher scores mean a worse outcome. Reduction in score indicates improvement.

Outcome measures

Outcome measures
Measure	9.6 mg of LV-101 n=40 Participants 9.6 mg of LV-101 during the 8-week placebo-controlled period 9.6 mg intranasal carbetocin: three times per day with meals	3.2 mg of LV-101 n=39 Participants 3.2 mg of LV-101 during the 8-week placebo controlled period 3.2 mg intranasal carbetocin: three times per day with meals	Placebo n=40 Participants Matched intranasal placebo during the 8-week placebo controlled period placebo: three times per day with meals
Anxiety	-4.306 score on a scale Interval -6.797 to -1.815	-8.301 score on a scale Interval -10.79 to -5.811	-4.489 score on a scale Interval -6.942 to -2.037

SECONDARY outcome

Timeframe: Week 8

Clinical Global Impression of Change (CGI-C) score versus placebo. Score range: 1-7; higher scores mean a worse outcome. Reduction in score indicates improvement.

Outcome measures

Outcome measures
Measure	9.6 mg of LV-101 n=40 Participants 9.6 mg of LV-101 during the 8-week placebo-controlled period 9.6 mg intranasal carbetocin: three times per day with meals	3.2 mg of LV-101 n=39 Participants 3.2 mg of LV-101 during the 8-week placebo controlled period 3.2 mg intranasal carbetocin: three times per day with meals	Placebo n=40 Participants Matched intranasal placebo during the 8-week placebo controlled period placebo: three times per day with meals
Global Impression	3.582 score on a scale Interval 3.25 to 3.913	3.395 score on a scale Interval 3.057 to 3.733	3.893 score on a scale Interval 3.562 to 4.225

SECONDARY outcome

Timeframe: Baseline to Week 8

Change in hyperphagia as measured by the change in specified subsets of HQ-CT questions versus placebo. Score range: 0-24; higher scores mean a worse outcome. Reduction in score indicates improvement.

Outcome measures

Outcome measures
Measure	9.6 mg of LV-101 n=40 Participants 9.6 mg of LV-101 during the 8-week placebo-controlled period 9.6 mg intranasal carbetocin: three times per day with meals	3.2 mg of LV-101 n=39 Participants 3.2 mg of LV-101 during the 8-week placebo controlled period 3.2 mg intranasal carbetocin: three times per day with meals	Placebo n=40 Participants Matched intranasal placebo during the 8-week placebo controlled period placebo: three times per day with meals
Hyperphagia Behavior (Subset)	-3.295 score on a scale Interval -4.667 to -1.922	-4.621 score on a scale Interval -6.01 to -3.233	-2.209 score on a scale Interval -3.577 to -0.841

Adverse Events

9.6 mg of LV-101

Serious events: 0 serious events

Other events: 20 other events

Deaths: 0 deaths

3.2 mg of LV-101

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	9.6 mg of LV-101 n=44 participants at risk 9.6 mg of LV-101 during the 8-week placebo controlled period 9.6 mg intranasal carbetocin: three times per day with meals	3.2 mg of LV-101 n=43 participants at risk 3.2 mg of LV-101 during the 8-weeks placebo-controlled period 3.2 mg intranasal carbetocin: three times per day with meals	Placebo n=43 participants at risk Matched intranasal placebo during 8-week placebo-controlled period placebo: three times per day with meals
Gastrointestinal disorders Diarrhea	4.5% 2/44 • Number of events 2 • 8-week placebo-controlled period	9.3% 4/43 • Number of events 5 • 8-week placebo-controlled period	2.3% 1/43 • Number of events 1 • 8-week placebo-controlled period
General disorders Pyrexia	0.00% 0/44 • 8-week placebo-controlled period	7.0% 3/43 • Number of events 3 • 8-week placebo-controlled period	0.00% 0/43 • 8-week placebo-controlled period
General disorders Upper respiratory tract infection	4.5% 2/44 • Number of events 2 • 8-week placebo-controlled period	7.0% 3/43 • Number of events 4 • 8-week placebo-controlled period	4.7% 2/43 • Number of events 2 • 8-week placebo-controlled period
Nervous system disorders Headache	9.1% 4/44 • Number of events 4 • 8-week placebo-controlled period	16.3% 7/43 • Number of events 8 • 8-week placebo-controlled period	7.0% 3/43 • Number of events 6 • 8-week placebo-controlled period
Respiratory, thoracic and mediastinal disorders Epistaxis	13.6% 6/44 • Number of events 7 • 8-week placebo-controlled period	2.3% 1/43 • Number of events 2 • 8-week placebo-controlled period	2.3% 1/43 • Number of events 2 • 8-week placebo-controlled period
Respiratory, thoracic and mediastinal disorders Nasal discomfort	4.5% 2/44 • Number of events 2 • 8-week placebo-controlled period	7.0% 3/43 • Number of events 3 • 8-week placebo-controlled period	2.3% 1/43 • Number of events 1 • 8-week placebo-controlled period
Vascular disorders Flushing	20.5% 9/44 • Number of events 10 • 8-week placebo-controlled period	14.0% 6/43 • Number of events 6 • 8-week placebo-controlled period	0.00% 0/43 • 8-week placebo-controlled period
Infections and infestations Nasopharyngitis	2.3% 1/44 • Number of events 1 • 8-week placebo-controlled period	0.00% 0/43 • 8-week placebo-controlled period	7.0% 3/43 • Number of events 3 • 8-week placebo-controlled period

Additional Information

Vice President of Clinical Development

Levo Therapeutics

Phone: 1-847-901-9260

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee This study is a multi-center study. Sponsor retains first publication rights for a period of time after conclusion of study. Study has not yet completed.
Publication restrictions are in place

Restriction type: OTHER