Trial Outcomes & Findings for Plerixafor Versus G-CSF in the Treatment of People With WHIM Syndrome (NCT NCT02231879)

NCT ID: NCT02231879

Last Updated: 2023-04-07

Results Overview

The primary outcome is a Total Infection Severity Score (TISS). Each infection during the 12 month period of treatment on each drug was scored for severity on a scale of 1-10 with higher scores representing more severe infections and then these scores were summed (weighted based on time at risk) to create a total infection severity score (TISS) in each period for each participant (range 0 to infinity). Drug failures during a period were pre-defined to count as more extreme than any TISS score. The primary analysis outcome is based on the Difference in Total Infection Severity Score (TISS) in Period 1 minus TISS in Period 2 analysis, with drug failures in only one period assigned the highest absolute value for the difference, with the sign defined according to the treatment order (e.g., negative for period 2 drug failures only). Higher values of the difference represent a worse outcome in the first period than in the second period. Thus, each participant's infection severity

• Recruitment status: COMPLETED
• Study phase: PHASE2/PHASE3
• Target enrollment: 20 participants
• Primary outcome timeframe: Scores from 12 months treatment on each study drug
• Results posted on: 2023-04-07

Participant Flow

1 subject could not tolerate minimal possible dose of G-CSF (Neupogen) 15 micrograms subcutaneously twice daily during screening period and was not randomized

Participant milestones

Measure	Plerixafor First Then Filgrastim G-CSF or plerixafor, blinded Plerixafor: Twice daily low dose injection for 14 months. G-CSF: Twice daily low dose injection for 14 months.	Filgrastim First Then Plerixafor G-CSF or plerixafor, blinded Plerixafor: Twice daily low dose injection for 14 months. G-CSF: Twice daily low dose injection for 14 months.
Overall Study STARTED	10	9
Overall Study COMPLETED	8	7
Overall Study NOT COMPLETED	2	2

Reasons for withdrawal

Measure	Plerixafor First Then Filgrastim G-CSF or plerixafor, blinded Plerixafor: Twice daily low dose injection for 14 months. G-CSF: Twice daily low dose injection for 14 months.	Filgrastim First Then Plerixafor G-CSF or plerixafor, blinded Plerixafor: Twice daily low dose injection for 14 months. G-CSF: Twice daily low dose injection for 14 months.
Overall Study Adverse Event	2	1
Overall Study Lack of Efficacy	0	1

Baseline Characteristics

Plerixafor Versus G-CSF in the Treatment of People With WHIM Syndrome

Baseline characteristics by cohort

Measure	Plerixafor First Then Filgrastim n=10 Participants G-CSF or plerixafor, blinded Plerixafor: Twice daily low dose injection for 14 months. G-CSF: Twice daily low dose injection for 14 months.	Filgrastim First Then Plerixafor n=9 Participants G-CSF or plerixafor, blinded Plerixafor: Twice daily low dose injection for 14 months. G-CSF: Twice daily low dose injection for 14 months.	Total n=19 Participants Total of all reporting groups
Age, Categorical <=18 years	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	9 Participants n=5 Participants	5 Participants n=7 Participants	14 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	5 Participants n=7 Participants	13 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 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
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	8 participants n=5 Participants	7 participants n=7 Participants	15 participants n=5 Participants
Region of Enrollment El Salvador	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment Sweden	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment Spain	0 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants

PRIMARY outcome

Timeframe: Scores from 12 months treatment on each study drug

Population: There are 19 participants that started both periods, 1 participant had drug failure during both periods, 3 participants had drug failure only during the period on Plerixafor. The outcome measure data table only summarizes the periods that were not drug failures, but the primary analysis includes the treatment failure periods by giving them the most extreme score (see Statistical Analysis section).

The primary outcome is a Total Infection Severity Score (TISS). Each infection during the 12 month period of treatment on each drug was scored for severity on a scale of 1-10 with higher scores representing more severe infections and then these scores were summed (weighted based on time at risk) to create a total infection severity score (TISS) in each period for each participant (range 0 to infinity). Drug failures during a period were pre-defined to count as more extreme than any TISS score. The primary analysis outcome is based on the Difference in Total Infection Severity Score (TISS) in Period 1 minus TISS in Period 2 analysis, with drug failures in only one period assigned the highest absolute value for the difference, with the sign defined according to the treatment order (e.g., negative for period 2 drug failures only). Higher values of the difference represent a worse outcome in the first period than in the second period. Thus, each participant's infection severity

Outcome measures

Measure	G-CSF (Both Periods Combined) n=18 Participants This group of observations are the outcomes (TISS=total infection severity score) during the period when each participant received G-CSF (i.e., filgrastim). Since each participant had one period on G-CSF, we have outcomes on all participants that started in participant flow, except those that had treatment failure. Recall, this is a crossover trial, where participants were randomized to receive either (PG) Plerixafor in Period 1 then G-CSF (i.e., filgrastim) ( in Period 2 or (GP) G-CSF in Period 1 then Plerixafor in Period 2. For example participants randomized to PG were given plerixafor twice daily subcutaneously for a total of 14 months (2 months dose adjustment followed by 12 months of treatment where infections and other parameters were evaluated) then crossover occurred and G-CSF was given twice daily subcutaneously over a total of 14 months (2 months dose adjustment followed by 12 months of treatment where infections and other parameters were evaluated).	Plerixafor (Both Periods Combined) n=15 Participants This group of observations are the outcomes (TISS=total infection severity score) during the period when each participant received Plerixafor. Since each participant had one period on Plerixafor, we have outcomes on all participants that started in participant flow, except those that had treatment failure. Recall, this is a crossover trial, where participants were randomized to receive either (PG) Plerixafor in Period 1 then G-CSF (i.e., filgrastim) ( in Period 2 or (GP) G-CSF in Period 1 then Plerixafor in Period 2. For example participants randomized to PG were given plerixafor twice daily subcutaneously for a total of 14 months (2 months dose adjustment followed by 12 months of treatment where infections and other parameters were evaluated) then crossover occurred and G-CSF was given twice daily subcutaneously over a total of 14 months (2 months dose adjustment followed by 12 months of treatment where infections and other parameters were evaluated).
Severity of Infection	12.5 score on a scale (with no maximum) Interval 0.0 to 36.0	9 score on a scale (with no maximum) Interval 0.0 to 24.0

PRIMARY outcome

Timeframe: Scores from 12 months treatment on each study drug

Population: The two populations are the two randomization arms in the crossover trial.

The primary outcome is a difference: the Total Infection Severity Score (TISS) in Period 1 minus the TISS in Period 2. Higher values represent a worse outcome in the first period than in the second period. Each infection during the 12 month period of treatment on each drug was scored for severity on a scale of 1-10 with higher scores representing more severe infections and then these individual infection scores were summed (weighted by time at risk) to create a total infection severity score (TISS) in each period. Because there is no pre-determined number of infections, the range is -infinity to +infinity. If a participant has a drug failure in only one period, their difference rank is either the highest rank (if the failure is in Period 1) or the lowest rank (if the failure is in Period 2), failure on both periods gives a difference of 0. 1 subject failed on both treatments, and 3 subjects failed only on plerixafor.

Outcome measures

Measure	G-CSF (Both Periods Combined) n=10 Participants This group of observations are the outcomes (TISS=total infection severity score) during the period when each participant received G-CSF (i.e., filgrastim). Since each participant had one period on G-CSF, we have outcomes on all participants that started in participant flow, except those that had treatment failure. Recall, this is a crossover trial, where participants were randomized to receive either (PG) Plerixafor in Period 1 then G-CSF (i.e., filgrastim) ( in Period 2 or (GP) G-CSF in Period 1 then Plerixafor in Period 2. For example participants randomized to PG were given plerixafor twice daily subcutaneously for a total of 14 months (2 months dose adjustment followed by 12 months of treatment where infections and other parameters were evaluated) then crossover occurred and G-CSF was given twice daily subcutaneously over a total of 14 months (2 months dose adjustment followed by 12 months of treatment where infections and other parameters were evaluated).	Plerixafor (Both Periods Combined) n=9 Participants This group of observations are the outcomes (TISS=total infection severity score) during the period when each participant received Plerixafor. Since each participant had one period on Plerixafor, we have outcomes on all participants that started in participant flow, except those that had treatment failure. Recall, this is a crossover trial, where participants were randomized to receive either (PG) Plerixafor in Period 1 then G-CSF (i.e., filgrastim) ( in Period 2 or (GP) G-CSF in Period 1 then Plerixafor in Period 2. For example participants randomized to PG were given plerixafor twice daily subcutaneously for a total of 14 months (2 months dose adjustment followed by 12 months of treatment where infections and other parameters were evaluated) then crossover occurred and G-CSF was given twice daily subcutaneously over a total of 14 months (2 months dose adjustment followed by 12 months of treatment where infections and other parameters were evaluated).
Difference in Total Infection Severity Score	10.6 score on a scale Interval 1.0 to 19.0	9.33 score on a scale Interval 1.0 to 19.0

Adverse Events

G-CSF

Serious events: 6 serious events

Other events: 19 other events

Deaths: 0 deaths

Plerixafor

Serious events: 2 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Measure	G-CSF n=19 participants at risk Twice daily low dose injection for 14 months.	Plerixafor n=19 participants at risk Twice daily low dose injection for 14 months.
Infections and infestations Flu-like illness	5.3% 1/19 • Number of events 1 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	0.00% 0/19 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Musculoskeletal and connective tissue disorders Arthritis	5.3% 1/19 • Number of events 1 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	5.3% 1/19 • Number of events 1 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Infections and infestations pneumonia	5.3% 1/19 • Number of events 1 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	0.00% 0/19 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Infections and infestations Urinary tract infection	5.3% 1/19 • Number of events 1 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	0.00% 0/19 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Infections and infestations Appendicitis	5.3% 1/19 • Number of events 1 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	0.00% 0/19 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Infections and infestations Cellulitis	0.00% 0/19 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	5.3% 1/19 • Number of events 1 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Nervous system disorders Transient ischemic attack	5.3% 1/19 • Number of events 1 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	0.00% 0/19 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.

Other adverse events

Measure	G-CSF n=19 participants at risk Twice daily low dose injection for 14 months.	Plerixafor n=19 participants at risk Twice daily low dose injection for 14 months.
Blood and lymphatic system disorders Iron Deficiency Anemia	5.3% 1/19 • Number of events 3 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	5.3% 1/19 • Number of events 2 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Blood and lymphatic system disorders Splenomegaly	10.5% 2/19 • Number of events 2 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	0.00% 0/19 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Blood and lymphatic system disorders Anemia	5.3% 1/19 • Number of events 1 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	5.3% 1/19 • Number of events 1 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Ear and labyrinth disorders Tinnitus	10.5% 2/19 • Number of events 2 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	5.3% 1/19 • Number of events 1 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Gastrointestinal disorders Nausea	31.6% 6/19 • Number of events 13 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	5.3% 1/19 • Number of events 1 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Gastrointestinal disorders Diarrhea	10.5% 2/19 • Number of events 3 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	5.3% 1/19 • Number of events 1 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Gastrointestinal disorders Vomiting	10.5% 2/19 • Number of events 2 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	0.00% 0/19 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Skin and subcutaneous tissue disorders Injection Site Reaction	0.00% 0/19 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	15.8% 3/19 • Number of events 5 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Infections and infestations Acute bronchitis	47.4% 9/19 • Number of events 19 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	10.5% 2/19 • Number of events 7 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Infections and infestations Upper Respiratory Tract Infection	26.3% 5/19 • Number of events 8 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	31.6% 6/19 • Number of events 11 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Infections and infestations Upper respiratory infection	10.5% 2/19 • Number of events 5 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	15.8% 3/19 • Number of events 7 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Infections and infestations Otitis media	31.6% 6/19 • Number of events 8 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	5.3% 1/19 • Number of events 4 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Infections and infestations Gastroenteritis	31.6% 6/19 • Number of events 8 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	0.00% 0/19 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Infections and infestations Herpes simplex	15.8% 3/19 • Number of events 5 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	10.5% 2/19 • Number of events 3 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Infections and infestations Urinary Tract Infection	21.1% 4/19 • Number of events 6 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	10.5% 2/19 • Number of events 2 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Infections and infestations Acute sinusitis	21.1% 4/19 • Number of events 5 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	10.5% 2/19 • Number of events 2 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Infections and infestations Abscess	10.5% 2/19 • Number of events 4 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	10.5% 2/19 • Number of events 2 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Infections and infestations Pharyngitis	10.5% 2/19 • Number of events 3 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	10.5% 2/19 • Number of events 2 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Infections and infestations Pneumonia	21.1% 4/19 • Number of events 4 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	0.00% 0/19 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Infections and infestations Skin Infection	10.5% 2/19 • Number of events 2 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	5.3% 1/19 • Number of events 1 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Infections and infestations Tinea capitis	5.3% 1/19 • Number of events 1 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	5.3% 1/19 • Number of events 2 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Infections and infestations Conjunctivitis	10.5% 2/19 • Number of events 3 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	0.00% 0/19 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Infections and infestations Infectious Diarrhea	5.3% 1/19 • Number of events 2 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	5.3% 1/19 • Number of events 1 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Infections and infestations Tinea corporis	0.00% 0/19 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	10.5% 2/19 • Number of events 2 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Infections and infestations Herpes labialis	10.5% 2/19 • Number of events 2 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	0.00% 0/19 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Injury, poisoning and procedural complications Fracture	0.00% 0/19 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	10.5% 2/19 • Number of events 2 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Injury, poisoning and procedural complications Ankle sprain	10.5% 2/19 • Number of events 2 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	0.00% 0/19 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Investigations Alanine aminotransferase increased	21.1% 4/19 • Number of events 5 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	10.5% 2/19 • Number of events 2 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Investigations Aspartate aminotransferase increased	21.1% 4/19 • Number of events 5 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	5.3% 1/19 • Number of events 2 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Investigations Blood alkaline phosphatase increased	15.8% 3/19 • Number of events 3 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	15.8% 3/19 • Number of events 4 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Investigations Weight gain	10.5% 2/19 • Number of events 2 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	26.3% 5/19 • Number of events 5 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Investigations Creatinine increased	10.5% 2/19 • Number of events 2 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	10.5% 2/19 • Number of events 2 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Investigations Bone mineral content decreased	10.5% 2/19 • Number of events 2 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	5.3% 1/19 • Number of events 1 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Investigations CPK increased	10.5% 2/19 • Number of events 2 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	0.00% 0/19 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Metabolism and nutrition disorders Hyperuricemia	21.1% 4/19 • Number of events 6 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	15.8% 3/19 • Number of events 3 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Metabolism and nutrition disorders Hyperglycemia	21.1% 4/19 • Number of events 5 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	5.3% 1/19 • Number of events 2 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Metabolism and nutrition disorders Hypernatremia	15.8% 3/19 • Number of events 3 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	5.3% 1/19 • Number of events 1 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Metabolism and nutrition disorders Hypocalcemia	5.3% 1/19 • Number of events 1 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	15.8% 3/19 • Number of events 3 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Metabolism and nutrition disorders Hyperkalemia	10.5% 2/19 • Number of events 2 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	5.3% 1/19 • Number of events 1 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Musculoskeletal and connective tissue disorders Bone pain	73.7% 14/19 • Number of events 41 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	36.8% 7/19 • Number of events 7 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Musculoskeletal and connective tissue disorders Knee pain	26.3% 5/19 • Number of events 5 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	10.5% 2/19 • Number of events 4 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Musculoskeletal and connective tissue disorders Joint pain	10.5% 2/19 • Number of events 7 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	5.3% 1/19 • Number of events 1 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Musculoskeletal and connective tissue disorders Shoulder pain	15.8% 3/19 • Number of events 6 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	0.00% 0/19 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Musculoskeletal and connective tissue disorders Arthralgia	10.5% 2/19 • Number of events 2 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	10.5% 2/19 • Number of events 4 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Musculoskeletal and connective tissue disorders Low back pain	10.5% 2/19 • Number of events 2 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	5.3% 1/19 • Number of events 1 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Nervous system disorders Headache	31.6% 6/19 • Number of events 12 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	15.8% 3/19 • Number of events 5 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Nervous system disorders Migraine	5.3% 1/19 • Number of events 1 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	10.5% 2/19 • Number of events 2 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Reproductive system and breast disorders Ovarian cyst	15.8% 3/19 • Number of events 11 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	5.3% 1/19 • Number of events 1 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Respiratory, thoracic and mediastinal disorders Wheezing	10.5% 2/19 • Number of events 2 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	0.00% 0/19 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Skin and subcutaneous tissue disorders Rash	0.00% 0/19 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	15.8% 3/19 • Number of events 5 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Skin and subcutaneous tissue disorders Papular rash	5.3% 1/19 • Number of events 2 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	10.5% 2/19 • Number of events 2 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Skin and subcutaneous tissue disorders Pruritic rash	5.3% 1/19 • Number of events 1 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	10.5% 2/19 • Number of events 2 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Skin and subcutaneous tissue disorders Acne	10.5% 2/19 • Number of events 2 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	0.00% 0/19 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Surgical and medical procedures Elective surgery	10.5% 2/19 • Number of events 4 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	10.5% 2/19 • Number of events 2 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.
Surgical and medical procedures Tooth extraction	10.5% 2/19 • Number of events 2 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.	10.5% 2/19 • Number of events 2 • up to 14 months on each study drug Definitions were identical to those as listed on clinicaltrials.gov. Adverse events were obtained from repeated in-person participant evaluation approximately every 4 months and laboratory testing approximately every 2 months during each drug treatment.

Additional Information

Dr. David H. McDermott

LMI/NIAID/NIH

Phone: 301-761-6647

Email: dmcdermott@niaid.nih.gov

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place